Science Volume 302, Number 5643, 10 Oct 2003, 290-292

Does Rejection Hurt? An fMRI Study of Social Exclusion

Naomi I. Eisenberger,1* Matthew D. Lieberman,1 Kipling D. Williams2

            A neuroimaging study examined the neural correlates of social exclusion and tested the hypothesis that the brain bases of social pain are similar to those of physical pain. Participants were scanned while playing a virtual ball-tossing game in which they were ultimately excluded. Paralleling results from physical pain studies, the anterior cingulate cortex (ACC) was more active during exclusion than during inclusion and correlated positively with self-reported distress. Right ventral prefrontal cortex (RVPFC) was active during exclusion and correlated negatively with self-reported distress. ACC changes mediated the RVPFC-distress correlation, suggesting that RVPFC regulates the distress of social exclusion by disrupting ACC activity.




Psychosomatic Medicine 65:276-283 (2003)

Social Support and Experimental Pain

Jennifer L. Brown, MA, David Sheffield, PhD, Mark R. Leary, PhD and Michael E. Robinson,            OBJECTIVE: The purpose of this experimental study was to supplement and expand on clinical research demonstrating that the provision of social support is associated with lower levels of acute pain.  METHODS: Undergraduates (52 men and 49 women) performed the cold pressor task either alone or accompanied by a friend or stranger who provided active support, passive support, or interaction. Pain perception was measured on a 10-point scale.

RESULTS: Participants in the active support and passive support conditions reported less pain than participants in the alone and interaction conditions, regardless of whether they were paired with a friend or stranger.  CONCLUSIONS: These data suggest that the presence of an individual who provides passive or active support reduces experimental pain.



Journal of Rehabilitation Research and Development Vol. 40, No. 5, Sept/Oct 2003 Pages 397–

An examination of the relationship between chronic pain and post-traumatic stress disorder

John D. Otis, PhD; Terence M. Keane, PhD; Robert D. Kerns, PhD

            Abstract—Chronic pain and post-traumatic stress disorder (PTSD) are frequently observed within the Department of Veterans Affairs healthcare system and are often associated with a significant level of affective distress and physical disability. Clinical practice and research suggest that these two conditions co-occur at a high rate and may interact in such a way as to negatively impact the course of either disorder; however, relatively little research has been conducted in this area. This review summarizes the current literature pertaining to the prevalence and development of chronic pain and PTSD. Research describing the comorbidity of both conditions is reviewed, and several theoretical models are presented to explain the mechanisms by which these two disorders may be maintained. Future directions for research and clinical implications are discussed.



British Medical Bulletin 65:223-234 (2003)

Headache: lessons learned from functional imaging

Arne May

Department of Neurology, University of Regensburg, Regensburg, Germany

            Most idiopathic headache syndromes are still recognized as vascular headaches although the clinical picture points towards a central triggering cause. The early functional imaging work using PET shed light on the genesis of some syndromes, implying that the observed activation in migraine (brainstem) and in cluster headache (hypothalamic grey) is involved in the pain process in a permissive or triggering manner rather than simply as a response to first division nociception per se. Using the advanced method of voxel-based morphometry (VBM), it has been suggested that there is a correlation between the brain area activated particularly in acute cluster headache, the posterior hypothalamic grey matter, and some change in grey matter in the same region. Moreover, also in a PET study in cluster headache and experimental headache, a vasodilation of major basal vessels has been observed which is non-specific to the cause and most likely the effect of a trigemino-parasympathetic reflex. Taken together, functional neuroimaging in headache patients has revolutionised this area of study and provided unique insights into some of the commonest maladies in man, suggesting that migraine and cluster headache are primarily driven from the brain.




Volume 19, Issue 3 , July 2003, Pages 655-664

Pain modulates cerebral activity during cognitive performance

Florence Rémy, , a, Uta N. Frankensteina, Adina Mincica, Boguslaw Tomaneka and Patrick W. Stromana

a MR Technology, Institute for Biodiagnostics, National Research Council, Winnipeg, Manitoba, Canada

            Received 20 September 2002;  revised 4 February 2003;  accepted 14 February 2003. ; Available The present study investigates how pain modulates brain activity during the performance of a semantic cognitive task. Based on previous observations, we hypothesized that a simultaneous painful stimulus will induce an activation increase in brain regions engaged in the cognitive task. High-field BOLD-fMRI experiments were conducted on 12 young healthy subjects, using a 2 × 2 factorial design. Painful stimuli were induced by thermal hot stimulation (46–49°C) on the palmar surface of the hand, using a contact thermode. Cognitive tasks consisted of either word generation (category fluency) or word repetition. Brain activity owing to the semantic tasks in the group was highly consistent with previous neuroimaging studies. When the painful stimulus was added to the cognitive task, activity in brain regions involved in semantic cognition, such as Broca's area, was increased (P < 0.01). Pain also modulated activity in brain areas not directly engaged in cognition. A positive modulation effect was observed in the midcingulate and the dorsomedial prefrontal cortex (P < 0.05). A negative modulation effect was observed in perigenual cingulate cortex, insula, and medial thalamus (P < 0.05).





Journal of Clinical Psychology

Early View   (Articles online in advance of print)

Stressful events, appraisal, coping and recurrent headache

Nicholas Marlowe *

Prince Henry Hospital, New South Wales, Australia

            One hundred fourteen headache sufferers recorded their headaches, stressful events, appraisal processes, and coping responses over a 28 day period. Stressful events were found to precede headache attacks more often than periods of headache freedom. Primary appraisals (how much the event mattered), levels of affective regulation coping and ratings of emotional upset were all higher for stressful events that were not associated with subsequent headache. Stressful events occurring during headache were followed by increases in the intensity of the attack. In such instances, avoidance coping was associated with higher ratings of headache intensity following the event and direct coping with lower post-event ratings. It was concluded that stressful events may be causally related to headache and that the ways in which headache sufferers respond to these events may also have implications for the onset and intensity of attack




Cephalalgia. 2003;23 Suppl 1:1-4.

Peripheral and central activation of trigeminal pain pathways in migraine: data from experimental animal models.

Buzzi MG, Tassorelli C, Nappi G.

IRCCS Neuromed, Pozzilli, Italy.

            EEG-studies in migraine in the last decade has contributed modestly to the understanding of headache pathogenesis. Headache patient groups seem to have increased EEG responses to photic stimulation, but a useful biological marker for migraine in single patients has not been found. In future EEG and QEEG studies we recommend to use follow-up designs and record several EEGs across the migraine cycle. It is also important to use a blinded study design in order to avoid selection bias. A clinical EEG should be performed in patients with acute headache attacks when either epilepsy, basilar migraine, migraine with prolonged aura or alternating hemiplegia is suspected. Unequivocal epileptiform abnormalities usually suggest a diagnosis of epilepsy. In children with occipital spike-wave activity the probable diagnosis is childhood epilepsy with occipital paroxysms (CEOP). The final diagnosis of either an epilepsy syndrome or migraine must be mainly based on a clinical judgement.



Clinical Neurophysiology

Article in Press, Corrected Proof - Note to users

Short-term plastic changes of the human nociceptive system following acute pain induced by capsaicin

Massimiliano Valeriani, , a, b, Lars Arendt-Nielsenc, Domenica Le Peraa, d, Domenico Restucciaa, Tiziana Rossoe, Liala De Armasa, d, Toni Maiesea, Antonio Fiaschie, Pietro Tonalia and Michele Tinazzie

Objective: To investigate possible neuroplastic changes induced by pain in cerebral areas devoted to nociceptive input processing.

Methods: CO2 laser-evoked potentials (LEPs) were recorded from 10 healthy subjects after stimulation of the right and left hand dorsum. Acute pain was obtained by topical application of capsaicin on the skin of right hand dorsum. LEPs were recorded after right and left hand stimulation before capsaicin, at the peak pain and 10–20 min after capsaicin removal. Right hand LEPs were evoked by laser stimuli delivered over the zone of secondary hyperalgesia during capsaicin and on both the zones of primary and secondary hyperalgesia after capsaicin removal.

Results: After right hand stimulation, the vertex LEPs, which are generated in the cingulate cortex, were significantly decreased in amplitude during capsaicin application and after capsaicin removal. Moreover, the topography of these potentials was modified after capsaicin removal, shifting from the central toward the parietal region. Dipolar modelling showed that the dipolar source in the anterior cingulate cortex moved backward after capsaicin removal. All these changes were not observed after stimulation of the left hand, contralateral to the application of capsaicin, thus suggesting that functional changes are selective for the painful skin and the adjacent territories. Conclusions: Our results suggest that acute cutaneous pain may inhibit the neural activity in regions of central nervous system processing nociceptive inputs and cortical representation of these inputs can be rapidly modified in presence of acute pain.



Clinical Neurophysiology

Volume 114, Issue 8 , August 2003, Pages 1497-1506

The disruptive effect of chronic pain on mismatch negativity

B. D. Dick, , J. F. Connolly, P. J. McGrath, G. A. Finley, G. Stroink, M. E. Houlihan and A. J. Clark

Dalhousie University, IWK Health Centre, QEII Health Sciences Centre, Halifax, NS, Canada

            Objective: To investigate the effect of chronic pain on processes that generate the mismatch negativity (MMN).

Methods:Twelve participants with a diagnosis of chronic intractable pain were tested before and after pain treatment. During testing, event-related potentials were recorded while participants performed tasks of varying difficulty.

Results: The amplitude of the MMN was found to be greater following a nerve block procedure compared to MMN amplitude when participants were experiencing chronic pain. This effect was found to occur in the MMN for difficult-to-detect tones elicited while participants were performing a simultaneous cognitively demanding visual task. MMN amplitude was found to be greater with attention to difficult-to-detect deviants during pain but not in no pain conditions.

Conclusions: These results provide an electrophysiological correlate of previous findings that high levels of pain disrupt cognition during the performance of demanding tasks.




Annual Review of Neuroscience

Mar 2003, Vol. 26, pp. 1-30

PAIN MECHANISMS: Labeled Lines Versus Convergence in Central Processing

A.D. (Bud) Craig

Atkinson Pain Research Laboratory, Barrow Neurological Institute, 350 W. Thomas Rd., Phoenix, Arizona 85013; email: bcraig@chw.edu

The issue of whether pain is represented by specific neural elements or by patterned activity within a convergent somatosensory subsystem has been debated for over a century. The gate control theory introduced in 1965 denied central specificity, and since then most authors have endorsed convergent wide-dynamic-range neurons. Recent functional and anatomical findings provide compelling support for a new perspective that views pain in humans as a homeostatic emotion that integrates both specific labeled lines and convergent somatic activity.




Pain Med. 2003 Jun;4(2):141-81.

A structured evidence-based review on the meaning of nonorganic physical signs: Waddell signs.

Fishbain DA, Cole B, Cutler RB, Lewis J, Rosomoff HL, Rosomoff RS.

Department of Psychiatry, University of Miami School of Medicine, Miami, Florida, USA. d.fishbain@miami.edu.

            STUDY DESIGN: This is a structured, evidence-based review of all available studies addressing the concept of nonorganic findings: Waddell signs (WSs). OBJECTIVES: To determine what evidence, if any, exists for the various interpretations for the presence of WSs on physical examination. SUMMARY OF BACKGROUND DATA: WSs are a group of eight physical findings divided into five categories, the presence of which has been alleged at times to have the following interpretations: Malingering/secondary gain, hysteria, psychological distress, magnified presentation, abnormal illness behavior, abnormal pain behavior, and somatic amplification. At the present time, there is, therefore, significant confusion as to what these findings mean. METHODS: A computer and manual literature search produced 61 studies and case series reports relating to WSs. These references were reviewed in detail, sorted, and placed into tabular form according to the following subject areas: 1) Reliability (test-retest); 2) Reliability (inter-rater); 3) Reliability (factor analysis); 4) Validity, psychological distress; 5) Validity, correlation Minnesota Multiphasic Pain Inventory (MMPI); 6) Validity, correlation abnormal illness behavior; 7) Validity, other behaviors; 8) Validity, as a nonorganic phenomenon; 9) Validity, correlation pain drawing; 10) Validity, functional performance; 11) Validity, treatment outcome; 12) Validity, predicting surgical treatment outcome; 13) Validity, return to work outcome; 14) Validity, secondary gain correlation; and 15) Validity, pain correlation. Each study in each topic area was classified according to the type of study it represented according to the type of evidence guidelines developed by the Agency for Health Care Policy and Research (AHCPR). In addition, a list of 14 study quality criteria was used to measure the quality of each study. Each study was categorized for each criterion as positive, (criterion filled), negative (criterion not filled), or not applicable independently by two of the authors. A percent quality score was obtained for each study by counting the total number of positives obtained, dividing by 14 minus the total number of not applicables, and multiplying by 100. Only studies having a quality score of 75% or greater were used to formulate the conclusions of this review. The strength and consistency of the evidence represented by the remaining studies in each topic area (above) was then categorized according to the strength and consistency AHCPR guidelines. Conclusions of this review for each topic area are based on these results. RESULTS OF DATA SYNTHESIS: Of the 61 studies, four had quality scores below 75% and were not used to generate the results of this review. According to the AHCPR guidelines for strength and consistency of the reviewed data, the following results were obtained: 1) There was consistent evidence for WSs being associated with decreased functional performance, poor nonsurgical treatment outcome, and greater levels of pain; 2) There was generally consistent evidence for WSs not being associated with psychological distress, abnormal illness behavior, or secondary gain; 3) There was also generally consistent evidence that WSs are an organic phenomenon and that they cannot be used to discriminate organic from nonorganic problems; 4) There was inconsistent evidence that WSs do demonstrate inter-rater reliability, do not correlate with the neurotic triad of the MMPI, are associated with poorer surgical treatment outcome, and are associated with nonreturn to work; 5) There was little or no evidence that WSs demonstrate test-retest reliability, or reliable factors, and are associated with self-esteem problems, catastrophizing, or the nonorganic pain drawing. CONCLUSIONS: Based on the above results, the following conclusions were made: 1) WSs do not correlate with psychological distress; 2) WSs do not discriminate organic from nonorganic problems; 3) WSs may represent an organic phenomenon; 4) WSs are associated with poorer treatment outcome; 5) WSs are associated with greater pain levels; 6) WSs are not associated with secondary gain; and 7) As a group, WS studies demonstrate some methodological problems.




Journal of Pain and Symptom Management

Volume 26, Issue 2 , August 2003, Pages 769-775

Hyperalgesia: An Emerging Iatrogenic Syndrome

Sebastiano Mercadante MD, Patrizia Ferrera MD, Patrizia Villari MD and Edoardo Arcuri MD

Clinical reports suggest that opioids, intended to abolish pain, can unexpectedly produce hyperalgesia. This paradoxical effect may be mechanistically related to tolerance induced by increasing doses of opioids. Two case reports illustrate a syndrome characterized by increasing pain pursued by escalating opioid doses, which results in a worsening of the clinical picture. Several experimental data may help explain the course of this challenging clinical condition. In escalating opioid doses rapidly, a risk of opioid-induced hyperalgesia should be recognized, as higher doses of opioids may stimulate rather than inhibit the central nervous system by different mechanisms. Alternative procedures should be taken into consideration to break this cycle, should it occur. More data are needed to detect this condition, as currently no diagnostic information on specific markers, clinical or biochemical, exists.





Article in Press, Corrected Proof - Note to users

Preoperative prediction of severe postoperative pain

C. J. Kalkman, , a, K. Visserb, J. Moena, G. J. Bonselc, D. E. Grobbeed and K. G. M. Moonsa, d

            We developed and validated a prediction rule for the occurrence of early postoperative severe pain in surgical inpatients, using predictors that can be easily documented in a preoperative setting. A cohort of surgical inpatients (n=1416) undergoing various procedures except cardiac surgery and intracranial neurosurgery in a University Hospital were studied. Preoperatively the following predictors were collected: age, gender, type of scheduled surgery, expected incision size, blood pressure, heart rate, Quetelet index, the presence and severity of preoperative pain, health-related quality of life the (SF-36), Spielberger's State–Trait Anxiety Inventory (STAI) and the Amsterdam Preoperative Anxiety and Information Scale (APAIS). The outcome was the presence of severe postoperative pain (defined as Numeric Rating Scale 8) within the first hour postoperatively. Multivariate logistic regression in combination with bootstrapping techniques (as a method for internal validation) was used to derive a stable prediction model. Independent predictors of severe postoperative pain were younger age, female gender, level of preoperative pain, incision size and type of surgery. The area under the receiver operator characteristic (ROC) curve was 0.71 (95% CI: 0.68–0.74). Adding APAIS scores (measures of preoperative anxiety and need for information), but not STAI, provided a slightly better model (ROC area 0.73). The reliability of this extended model was good (Hosmer and Lemeshow test p-value 0.78). We have demonstrated that severe postoperative pain early after awakening from general anesthesia can be predicted with a scoring rule, using a small set of variables that can be easily obtained from all patients at the preoperative visit. Before this internally validated preoperative prediction rule can be applied in clinical practice to support anticipatory pain management, external validation in other clinical settings is necessary.





Volume 104, Issue 3 , August 2003, Pages 509-517

Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery

Michele Sterling, , a, Gwendolen Julla, Bill Vicenzinoa and Justin Kenardyb

            Hypersensitivity to a variety of sensory stimuli is a feature of persistent whiplash associated disorders (WAD). However, little is known about sensory disturbances from the time of injury until transition to either recovery or symptom persistence. Quantitative sensory testing (pressure and thermal pain thresholds, the brachial plexus provocation test), the sympathetic vasoconstrictor reflex and psychological distress (GHQ-28) were prospectively measured in 76 whiplash subjects within 1 month of injury and then 2, 3 and 6 months post-injury. Subjects were classified at 6 months post-injury using scores on the Neck Disability Index: recovered (<8), mild pain and disability (10–28) or moderate/severe pain and disability (>30). Sensory and sympathetic nervous system tests were also measured in 20 control subjects. All whiplash groups demonstrated local mechanical hyperalgesia in the cervical spine at 1 month post-injury. This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms. Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests. These changes occurred within 1 month of injury and remained unchanged throughout the study period. Whilst no significant group differences were evident for the sympathetic vasoconstrictor response, the moderate/severe group showed a tendency for diminished sympathetic reactivity. GHQ-28 scores of the moderate/severe group were higher than those of the other two groups. The differences in GHQ-28 did not impact on any of the sensory measures. These findings suggest that those with persistent moderate/severe symptoms at 6 months display, soon after injury, generalised hypersensitivity suggestive of changes in central pain processing mechanisms. This phenomenon did not occur in those who recover or those with persistent mild symptoms.





PAIN. In Press

Hyperalgesia versus response bias in fibromyalgia

Roger B. Fillingim*


The findings of Petzke et al. (2003) further indicate that individuals with FM process nociceptive information differently than controls. There are inevitably multiple biopsychosocial factors that interact in complex ways to produce these alterations in pain sensitivity. The results of their research suggest that measures of pain sensitivity that are freer of response bias still demonstrate enhanced pain responses in FM. The mechanisms underlying the enhanced pain responses of FM patients remain to be determined, but the careful and systematic research described by Petzke et al.(2003) informs us that the enhanced pain sensitivity in FM is not an artifact of response bias. A more thorough understanding of the hyperalgesia observed in FM will help elucidate its pathophysiology, ultimately leading to more effective diagnosis and treatment of this complex and disabling syndrome.




Curr Pain Headache Rep. 2003 Oct;7(5):362-8.

Related Articles, Links

Epidemiology of fibromyalgia.

Neumann L, Buskila D.

Department of Epidemiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. lily@bgumail.bgu.ac.il

            Chronic widespread pain, the cardinal symptom of fibromyalgia (FM), is common in the general population, with comparable prevalence rates of 7.3% to 12.9% across different countries. The prevalence of FM in the general population was reported to range from 0.5% to 5% and up to 15.7% in the clinic. The common association of FM with other rheumatic disorders, chronic viral infections, and systemic illnesses has been well documented in several studies. Up to 65% of patients with systemic lupus erythematosus meet the criteria for FM. FM is considered a member of the family of functional somatic syndromes. These syndromes are very common and share a similar phenomenology, epidemiologic characteristics, high rates of occurrence, a common pathogenesis, and similar management strategies. A high prevalence of FM was demonstrated among relatives of patients with FM and it may be attributed to genetic and environmental factors.



Pain. 2003 Aug;104(3):665-72.

The effect of combined therapy (ultrasound and interferential current) on pain and sleep in fibromyalgia.

Almeida TF, Roizenblatt S, Benedito-Silva AA, Tufik S.

            Multidisciplinary treatment has proven to be the best therapeutic option to fibromyalgia (FM) and physiotherapy has an important role in this approach. Considering the controversial results of electrotherapy in this condition, the aim of this study was to assess the effects of combined therapy with pulsed ultrasound and interferential current (CTPI) on pain and sleep in FM. Seventeen patients fulfilling FM criteria were divided into two groups, CTPI and SHAM, and submitted to pain and sleep evaluations. Pain was evaluated by body map (BM) of the painful areas; quantification of pain intensity by visual analog scale (VAS); tender point (TP) count and tenderness threshold (TT). Sleep was assessed by inventory and polysomnography (PSG). After 12 sessions of CTPI or SHAM procedure, patients were evaluated by the same initial protocol. After treatment, CTPI group showed, before and after sleep, subjective improvement of pain in terms of number (BM) and intensity (VAS) of painful areas (P<0.001, both); as well as objective improvement, with decrease in TP count and increase in TT (P<0.001, both). Subjective sleep improvements observed after CTPI treatment included decrease in morning fatigue and in non-refreshing sleep complaint (P<0.001, both). Objectively, PSG in this group showed decrease in sleep latency (P<0.001) and in the percentage of stage 1 (P<0.001), increase in the percentage of slow wave sleep (P<0.001) and in sleep cycle count (P<0.001). Decrease in arousal index (P<0.001), number of sleep stage changes (P<0.05) and wake time after sleep onset (P<0.05), were also observed and no difference regarding pain or sleep parameters were verified after SHAM procedure. This study shows that CTPI can be an effective therapeutic approach for pain and sleep manifestations in FM.






Volume 19, Issue 4 , August 2003, Pages 1738-1747

Functional activity mapping of the mesial hemispheric wall during anticipation of pain

Carlo A. Porro, , a, Valentina Cettoloa, Maria Pia Francescatoa and Patrizia Baraldib

            The relative contributions of autonomic arousal and of cognitive processing to cortical activity during anticipation of pain, and the role of changes in thalamic outflow, are still largely unknown. To address these issues, we investigated with functional magnetic resonance imaging (fMRI) the activity of the contralateral mesial hemispheric wall in 56 healthy volunteers while they expected the stimulation of one foot, which could be either painful or innocuous. The waiting period was characterized by emotional arousal, a moderate rise in heart rate, and by increases in mean fMRI signals in the medial thalamus, mid- and posterior cingulate cortex, and in the putative foot area of the primary somatosensory and motor cortex. The same brain regions, excepting posterior cingulate, were also activated by somatosensory stimulation. We identified by cross-correlation analysis a cluster population whose fMRI signal time course was related to the mean heart rate (HR) profile, showing selective changes of activity during the waiting period. Positively correlated clusters were found mainly in sensorimotor areas, mid- and posterior cingulate, and dorsomedial prefrontal cortex. Negatively correlated clusters predominated in the perigenual anterior cingulate and ventromedial prefrontal cortex. HR clusters had different characteristics from, and showed limited spatial overlap with, clusters whose fMRI signals were related to the psychophysical pain intensity profile; however, both cluster populations were affected by anticipation. These findings unravel a complex pattern of brain activity during uncertain anticipation of noxious input, likely related both to changes in the level of arousal and to cognitive modulation of the pain system.




Rheumatology 2003; 42: 959-968

Risk factors for new-onset low back pain amongst cohorts of newly employed workers

E. F. Harkness1,, G. J. Macfarlane1,2, E. S. Nahit1,2, A. J. Silman1 and J. McBeth1

            Objectives. To test the hypothesis that work-related mechanical, psychosocial and physical environment factors would predict new-onset low back pain (LBP) in newly employed workers.  Methods. A total of 1186 newly employed workers were recruited from a variety of occupational settings. Those who were free from LBP at baseline were identified. Subjects were followed up at 12 and 24 months. Work-related mechanical, psychosocial and physical environment exposures were measured. Generalized estimating equations were used to assess predictors of new-onset LBP.  Results. New-onset LBP was reported by 119 (19%) and 81 (19%) subjects at 12 and 24 months, respectively. Several work-related mechanical exposures predicted new-onset LBP including lifting heavy weights with one or two hands, lifting heavy weights at or above shoulder level, pulling heavy weights, kneeling or squatting for 15 min or longer. Of the psychosocial factors examined, stressful and monotonous work significantly predicted symptom onset. In addition, hot working conditions and pain at other sites also predicted new-onset LBP. On multivariate analysis these risks were only moderately attenuated but the 95% confidence intervals excluded unity only for the latter, non-mechanical, exposures.  Conclusion. In this cohort of newly employed workers, from a range of occupations, several aspects of the work-place environment, other than mechanical factors, were important in predicting new-onset LBP. These results emphasize that interventions aimed at reducing the occurrence of LBP are likely to be most successful if they intervene across these domains.




Central Sensitization in Fibromyalgia and Other Musculoskeletal Disorders

Lars Arendt-Nielsen PhD and Thomas Graven-Nielsen PhD

Laboratory for Human Experimental Pain Research, Fredrik Bajers Vej 7 Building D3, Center for -Sensory-Motor Interaction Aalborg University, Aalborg, DK-9220, Denmark

Current Pain and Headache Reports 2003 7:355-361 (published 1 October 2003)

            Muscle hyperalgesia and referred pain play an important role in chronic musculoskeletal pain. New knowledge on the involved basic mechanisms and better methods to assess muscle pain in the clinic are needed to revise and optimize treatment regimens. Increased muscle sensitivity is manifested as pain evoked by a normally non-nociceptive stimulus (allodynia), increased pain intensity evoked by nociceptive stimuli (hyperalgesia), or increased referred pain areas with associated somatosensory changes. Some manifestations of sensitization, such as expanded referred muscle pain areas in patients with chronic musculoskeletal pain, can be explained from animal experiments showing extrasegmental spread of sensitization. An important part of the pain manifestations (eg, tenderness and referred pain) related to chronic musculoskeletal disorders may result from peripheral and central sensitization, which may play a role in the transition from acute to chronic pain.




Fibromyalgia, Hepatitis C Infection, and the Cytokine Connection

Mollie E Thompson MD and André Barkhuizen MD

Division of Arthritis and Rheumatic Diseases, 3181 Sam Jackson Park Road OP-09, Oregon Health Science University, Portland, OR, 97239, USA

Current Pain and Headache Reports 2003 7:342-347 (published 1 October 2003)

            Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 ß, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and theinfluence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.




J Negat Results Biomed. 2003 Aug 23;2(1):4.

Prospective Epidemiological Observations on the Course of the Disease in Fibromyalgia Patients.

Noller V, Sprott H.

Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Switzerland. haiko.sprott@usz.ch

            OBJECTIVES: The aim of the study was to carry out a survey in patients with fibromyalgia (FM), to examine their general health status and work incapacity (disability-pension status), and their views on the effectiveness of therapy received, over a two-year observation period. METHODS: 48 patients diagnosed with FM, according to the American College of Rheumatology (ACR) criteria, took part in the study. At baseline, and on average two years later, the patients underwent clinical investigation (dolorimetry, laboratory diagnostics, medical history taking) and completed the Fibromyalgia questionnaire (Dettmer and Chrostek 1). RESULTS: 27/48 (56%) patients participated in the two-year follow-up. In general, the patients showed no improvement in their symptoms over the observation period, regardless of the type of therapy they had received. General satisfaction with quality of life improved, as did satisfaction regarding health status and the family situation, although the degree of pain experienced remain unchanged. In comparison with the initial examination, there was no change in either work-capacity or disability-pension status. CONCLUSIONS: The FM patients showed no improvement in pain, despite the many various treatments received over the two-year period. The increase in general satisfaction over the observation period was believed to be the result of patient instruction and education about the disease. To what extent a population of patients with FM would show similar outcomes if they did not receive any instruction/education about their disorder, cannot be ascertained from the present study; and, indeed, the undertaking of a study to investigate this would be ethically questionable. As present, no conclusions can be made regarding the influence of therapy on the primary and secondary costs associated with FM.





Nordic Journal of Psychiatry

Volume 57, Number 1 / 2003, 61 - 66

Chronic pain disorder associated with psychogenic versus somatic factors: A comparative study. Michael Binzer, Michael Binzer, Michael Binzer

            Fifty-one consecutive non-depressed patients with chronic pain referred to a multidisciplinary pain clinic were assessed. In 32 patients, pain was judged to be associated with psychogenic factors only, while pain in 19 patients could be attributed solely to a general medical condition. The methods of investigation comprised visual analogue scales (VAS) and pain drawings, the Dysfunctional Attitude Scale (DAS), the Karolinska Scales of Personality (KSP), locus of control (LOC) and EMBU (for assessing perceived parental rearing practices). Mean age, gender distribution, analgesic consumption, pain duration, percentage of body area pain as well as body localization of pain were comparable in both groups. Patients with psychogenic pain reported higher levels of general bodily discomfort but less concentration difficulties and memory disturbances compared with the somatic pain patients. There were no significant intergroup differences on any of the LOC, DAS, KSP or EMBU items. LOC turned out to be extremely external, whereas DAS, KSP and EMBU scores were comparable to normal controls in earlier work. The paucity of differences between the two patient groups and the unremarkable personality structure of patients led to somewhat conflicting conclusions, and the results of the study pose one more piece of evidence for the futility of the dichotomous organic vs. psychogenic distinction of chronic pain disorders.



Psychological Bulletin  Volume 129(4)  July 2003  p 495–521

Hypnosis and Clinical Pain

Patterson, David R; Jensen, Mark P.

            Hypnosis has been demonstrated to reduce analogue pain, and studies on the mechanisms of laboratory pain reduction have provided useful applications to clinical populations. Studies showing central nervous system activity during hypnotic procedures offer preliminary information concerning possible physiological mechanisms of hypnotic analgesia. Randomized controlled studies with clinical populations indicate that hypnosis has a reliable and significant impact on acute procedural pain and chronic pain conditions. Methodological issues of this body of research are discussed, as are methods to better integrate hypnosis into comprehensive pain treatment.




Annual Review of Neuroscience, Jul 2003, Vol. 26, pp. 1-30

PAIN MECHANISMS: Labeled Lines Versus Convergence in Central Processing

A.D. (Bud) Craig; bcraig@chw.edu

            The issue of whether pain is represented by specific neural elements or by patterned activity within a convergent somatosensory subsystem has been debated for over a century. The gate control theory introduced in 1965 denied central specificity, and since then most authors have endorsed convergent wide-dynamic-range neurons. Recent functional and anatomical findings provide compelling support for a new perspective that views pain in humans as a homeostatic emotion that integrates both specific labeled lines and convergent somatic activity.


Annual Review of Pharmacology and Toxicology, In Press

Voltage-Gated Sodium Channels and Hyperalgesia

Josephine Lai, Frank Porreca, John C. Hunter, Michael S. Gold

Abstract Physiological and pharmacological evidence have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.




Rheumatology, In Press

The role of workplace low-level mechanical trauma, posture and environment in the onset of chronic widespread pain

J. McBeth*, E. F. Harkness, A. J. Silman, and G. J. Macfarlane; john.mcbeth@man.ac.uk.

            Background. We have recently demonstrated that individual psychosocial factors are important predictors of the onset of chronic widespread pain. It has been hypothesized that excessive mechanical exposure may also be associated with symptom onset, although this has not been formally examined. We therefore determined the relative contributions of individual psychosocial and work-related mechanical, posture and environment factors in symptom onset.

Methods. We conducted a population-based prospective survey and identified 1658 adults aged 18-65 yr who were symptom-free. At baseline, detailed information was obtained on work-related mechanical and environment factors using validated instruments. Individual psychosocial features were also measured. Subjects free of chronic widespread pain at baseline were followed up at 12 and 36 months to identify those reporting the onset of new symptoms.

Results. In all, 1445 (91%) returned the questionnaire at 12 months and 978 (89%) at 36 months. Of these, 81 and 92 respectively reported new chronic widespread pain. Symptom onset was predicted by workplace factors {pushing/pulling heavy weights [relative risk (RR) = 1.8, 95% confidence interval (CI) 1.1, 3.0]; repetitive movements of the wrists (RR = 1.8, 95% CI 1.2, 2.7); kneeling (RR = 2.2, 95% CI 1.2, 4.1)} and individual factors [aspects of illness behaviour (RR = 2.9, 95% CI 1.6, 5.3); somatic symptoms (RR = 1.9 95% CI 1.1, 3.3); fatigue (RR = 1.9, 95% CI 1.2, 3.1); baseline pain symptoms (RR = 2.5, 95% CI 1.6, 3.9)]. In multivariate analysis, pushing/pulling heavy weights, repetitive wrist movements, kneeling and other pain at baseline were associated with new-onset chronic widespread pain. However, the strongest predictor was a high score on the illness behaviour scale. Conclusion. This study provides only limited support for the hypothesis that low-level mechanical injury may be a risk factor for developing chronic widespread pain. The onset of chronic widespread pain appears to be multifactorial and is strongly predicted by individual psychosocial factors



Rheumatology, In Press

Does psychological vulnerability determine health-care utilization in fibromyalgia?

P. L. Dobkin, M. De Civita, S. Bernatsky, H. Kang, and M. Baron; patricia.dobkin@mcgill.ca.

            Objectives. Patients with fibromyalgia (FM) undergo multiple testing and referral to specialists, and often use complementary/alternative medicine (CAM) services. The objectives of the study were: (i) to document health service utilization, and (ii) to examine whether psychological vulnerability was associated with visits to physicians and CAM providers. Methods. Women (N = 178) with a diagnosis of primary FM completed a psychosocial test measuring pain, perceived stress, global psychological distress, sexual abuse history, co-morbidity and disability due to FM. Subjects also completed a health services questionnaire, documenting visits to physicians and CAM providers during the previous 6 months. Psychological vulnerability was operationalized as obtaining high scores on psychological distress, perceived stress and reporting at least one abusive event. Results. The average number of visits was 7.2 to physicians and 11.3 to CAM providers. Conclusions. The number of physician visits was significantly associated with more co-morbidity. Psychologically vulnerable subjects were more likely to use CAM services than those not so classified.



Rheumatology, In Press

A biopsychosocial model of pain and depression in rheumatoid arthritis: a 12-month longitudinal study

T. Covic, B. Adamson, D. Spencer, and G. Howe: tcovic@csu.edu.au.

            Objective. To cross-validate a biopsychosocial model using physical disability, helplessness and passive coping to predict depression and pain in rheumatoid arthritis (RA). Methods. Clinical and psychological measures were collected from 157 RA patients at three time points over a period of 12 months. Path analysis was used for cross-sectional and longitudinal prediction of depression and pain. Results. Helplessness and passive coping were found to be significant mediators of the relationship between the physical disability and future depression and pain. Cross-sectionally, the predictive model could account for 52-94% of the variance of pain and 37-71% of the variance of depression. Longitudinally, the predictive model could explain 29-43% of the variance of pain and 21-33% of the variance of depression. Conclusions. These results suggest that physical disability, helplessness and passive coping have a significant impact on the levels of pain and depression experienced by RA patients.



Pain, Article in Press

Blood pressure but not cortisol mediates stress effects on subsequent pain perception in healthy men and women

Mustafa al'Absi, and Karen L. Petersen

            Research has demonstrated that exposure to acute stress may attenuate pain perception. Mechanisms of this effect in humans have not been determined. This study was conducted to determine the extent to which psychophysiological and adrenocortical responses to acute stress predict subsequent pain perception. One hundred and fifty-two healthy participants (80 women) were assigned to one of two conditions: rest followed by the cold pressor test (CPT; N=76) or stress followed by CPT (N=76). The stress protocol consisted of a public-speaking challenge. Participants rated their pain every 15 s during a 90-s hand CPT (0–4 °C), and they completed the short form of the McGill Pain Questionnaire. Salivary cortisol, mood, blood pressure (BP), and impedance cardiography measures were collected in both conditions. Women had lower BP and reported greater pain than men in both conditions (ps<0.01). Participants in the stress condition reported less pain during CPT than those in the rest condition (p=0.02). Regression analyses demonstrated that the stress effect on pain ratings was mediated by systolic BP level during stress; however, cortisol responses did not affect this relationship. Mood changes were independent predictors of pain. The study demonstrates that BP changes in response to stress mediate the stress-induced attenuation of pain perception.



Experimental Neurology

Volume 184, Supplement 1 , November 2003, Pages 80-88

Insights into the pathophysiology of neuropathic pain through functional brain imaging

Kenneth L. Casey, , a, Jürgen Lorenzb and Satoshi Minoshimac

            We present here an example case of neuropathic pain with heat allodynia as a major symptom to illustrate how the functional imaging of pain may provide new insights into the pathophysiology of painful sensory disorders. Tissue injury of almost any kind, but especially peripheral or central neural tissue injury, can lead to long-lasting spinal and supraspinal re-organization that includes the forebrain. These forebrain changes may be adaptive and facilitate functional recovery, or they may be maladaptive, preventing or prolonging the painful condition, and interfering with treatment. In an experimental model of heat allodynia, we used functional brain imaging to show that: (1) the forebrain activity during heat allodynia is different from that during normal heat pain, and (2) during heat allodynia, specific cortical areas, specifically the dorsolateral prefrontal cortex, can attenuate specific components of the pain experience, such as affect, by reducing the functional connectivity of subcortical pathways. The forebrain of patients with chronic neuropathic pain may undergo pathologically induced changes that can impair the clinical response to all forms of treatment. Functional imaging, including PET, fMRI, and neurophysiological techniques, should help identify brain mechanisms that are critical targets for more effective and more specific treatments for chronic, neuropathic pain.





Volume 105, Issue 3 , October 2003, Pages 481-488

Analgesic and placebo effects of thalamic stimulation

Serge Marchand, Ron C. Kupers, M. Catherine Bushnell, and Gary H. Duncan

            Numerous clinical studies have reported successful relief of chronic pain with sensory thalamic stimulation. However, even with the extensive use of sensory thalamic stimulation as a clinical tool in the relief of chronic pain, the results are still inconsistent. This discrepancy could probably be explained by the fact that the majority of these studies are case reports or retrospective analyses, which have often used imprecise pain measurements that do not allow a rigorous statistical evaluation of pain relief. None of these studies measured the effect of stimulation on clinical pain for longer than a few hours per day, which is an important aspect considering that clinical pain can vary over time. Moreover, placebo controls are seldom included. In the current study, we measured patients' pain perception at home over a 2-week period, both during days of normal stimulation of the sensory thalamus and during days without stimulation. Patients also came to the laboratory to assess the effects of thalamic and placebo stimulation on clinical pain, experimental heat pain, innocuous air puff and visual stimulation. A potential relation between the perceived paresthesia and analgesic efficacy during thalamic and placebo stimulation was also explored. We found that thalamic stimulation significantly affected clinical and experimental pain perception, but that an important placebo component also exists. On the other hand, neither thalamic nor placebo stimulation affected air puff and visual ratings, suggesting that the effect applies specifically to pain and hence is not caused by a general change in attention. The level of paresthesia elicited during the placebo manipulation was also directly correlated with the degree of placebo pain relief. These results suggest that thalamic stimulation produces a small but significant reduction in pain perception, but that a significant placebo effect also exists.






Jensen, Mark P. PhD

Questionnaire Validation: A Brief Guide for Readers of the Research Literature.[Editorial]

Clinical Journal of Pain. 19(6):345-352, November/December 2003.

            Because of the importance of pain assessment to understanding the nature and scope of pain problems, and for testing the efficacy of pain treatments, new pain measures are frequently developed. Research that describes the development and evaluation of pain measures should include detailed information concerning the validity and reliability of the measures. However, for the findings from this research to be most useful, the consumers of this research (clinicians and researchers who use pain measures) should understand the concepts of validity and reliability, and the procedures used for evaluating these in pain assessment research. The purpose of this commentary is to provide a summary of these psychometric issues, using the study and findings of Krause and Backonja as an illustrative example of the concepts.



Kerr, Daniel P. DPhil; Walsh, Deirdre M. DPhil; Baxter, David DPhil

Acupuncture in the Management of Chronic Low Back Pain: A Blinded Randomized Controlled Trial.[Article]

Clinical Journal of Pain. 19(6):364-370, November/December 2003.

            Objective: To assess the efficacy of acupuncture in the treatment of chronic low back pain. Methods: Patients (n = 60) with chronic low back pain were recruited and randomly allocated to either Acupuncture therapy or Placebo transcutaneous electrical nerve stimulation (TENS) groups. Patients were treated weekly for 6 weeks, and blinded assessments were carried out pre- and post-treatment using the McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for pain, the Short-form 36 quality-of-life questionnaire, and a simple range of motion measurement. A total of 46 patients completed the trial and were followed up at 6 months. Results: Analysis of results using t tests showed that in both groups there were significant pre-post improvements for all scores, except for MPQ scores in the Placebo-TENS group. There was no significant difference between the 2 groups for any of the outcome measures at the end of treatment. Results from the 6-month follow-up would suggest that the response was better in the acupuncture group. Discussion: Further research is necessary to fully assess the efficacy of this treatment in combating chronic low back pain using larger sample sizes or alternative control groups.



Grabow, Theodore S. MD; Tella, Prabhav K. MBBS, MPH; Raja, Srinivasa N. MD

Spinal Cord Stimulation for Complex Regional Pain Syndrome: An Evidence-Based Medicine Review of the Literature.[Article]

Clinical Journal of Pain. 19(6):371-383, November/December 2003.

            Objectives: The purpose of this investigation is to assess the evidence for efficacy of SCS in the management of pain in patients with CRPS. Methods: Search strategy: Electronic databases such as Medline and Cochrane Library were queried using key words such as "spinal cord stimulation," "reflex sympathetic dystrophy (RSD)," and "complex regional pain syndrome (CRPS)." Selection criteria: Relevant published randomized controlled trials (RCT), cohort studies, case-control studies, case series, and case reports that described SCS as the primary treatment modality for patients with CRPS were eligible for inclusion. Data collection and analysis: Data extracted from qualified studies were summarized in sections of methodology, demographics, SCS equipment, primary and secondary outcomes, and complications. Results: Thirteen studies using the primary search strategy and 7 studies from their reference lists were considered. Five of these 20 studies were discarded. One RCT, 2 prospective observational, and 12 retrospective observational studies were eventually considered. The methodological quality of all studies was poor except for the single RCT study. Discussion: Although limited in quality and quantity, available evidence from the examined literature suggests that SCS is effective in the management of pain in patients with CRPS (grade B/C). Clinically useful information extracted from the available studies is very limited in guiding clinicians in the rational use of SCS for pain management in CRPS patients. Future attempts to investigate the efficacy of SCS in CRPS patients should involve methodologically robust designs such as randomized studies that have sufficient power.




J Trauma Stress. 2003 Oct;16(5):451-7.

A preliminary examination of treatment for posttraumatic stress disorder in chronic pain patients: a case study.

Shipherd JC, Beck JG, Hamblen JL, Lackner JM, Freeman JB.

            Manualized treatments have become popular, despite concern about their use when comorbid diagnoses are present. In this report, the efficacy of manualized posttraumatic stress disorder (PTSD) treatment was examined in the presence of chronic pain. Additionally, the effect of PTSD treatment on chronic pain and additional psychiatric diagnoses was explored. Six female patients with both PTSD and chronic pain following motor vehicle accidents were treated for PTSD using a multiple baseline design. The results indicate that manualized treatment for PTSD was effective in reducing PTSD symptoms in these patients. Although there were no changes in subjective pain, there were pain-related functional improvements and reductions in other psychiatric diagnoses for the majority of patients.




J Head Trauma Rehabil, Vol. 19, No. 1, pp. 2–X, 2004 (In Press).

The Problem of Pain

Keith Nicholson, PhD; Michael F. Martelli, PhD

            Pain problems, especially posttraumatic headache, are very common following head trauma. Pain may be the most significant problem, more disabling than any brain or other injuries, and interfering with aspects of cognition or other function. However, posttraumatic headache and most other chronic posttraumatic pain problems remain poorly understood. This article reviews fundamental issues that should be considered in understanding the nature of chronic pain including the distinction between acute and chronic pain; neurobiological distinctions between the lateral and medial pain system; nociceptive versus neuropathic or other central pain; sensitization effects; the widely accepted view of chronic pain as a multidimensional subjective experience involving sensory, motivational-affective and cognitive-behavioral components; the problem of mind-body dualism; the role of psychosocial factors in the onset, maintenance, exacerbation or severity of pain; plus issues of response bias and malingering.




J Head Trauma Rehabil, Vol. 19, No. 1, pp. 10–X, 2004

Psychological, Neuropsychological, and Medical Considerations in Assessment and Management of Pain

Michael F. Martelli, PhD; Nathan D. Zasler, MD; Mark C. Bender, PhD; Keith Nicholson, PhD

            Pain is a common yet challenging problem, particularly following traumatic injuries to the head or neck. It is a complex, multidimensional subjective experience with no clear or objective measures; yet it can have a significantly disabling effect across a wide range of functions. Persisting misconceptions owing to mind-body dualism have hampered advances in its understanding and treatment. In this article, a conceptualization of pain informed by recent research and derived from a more useful biopsychosocial model guides discussion of relevant medical, psychological, and neuropsychological considerations. This pain process model explains chronicity in terms of hyperresponsiveness and dysregulation of inhibitory or excitatory pain modulation mechanisms. Related neurocognitive effects of chronic pain are examined and recommendations for minimizing its confounding effects in neuropsyhological evaluations are offered. A biopsychosocial assessment model is presented to guide understanding of the myriad of factors that contribute to chronicity. A brief survey of general classes and samples of the more useful pain assessment instruments is included. Finally, this model offers a rational means of organizing and planning individually tailored pain interventions, and some of the most useful pharmacologic, physical, and behavioral strategies are reviewed.



Health Psychol. 2003 Nov;22(6):592-7.

Biological and psychological factors associated with memory function in fibromyalgia syndrome.

Sephton SE, Studts JL, Hoover K, Weissbecker I, Lynch G, Ho I, McGuffin S, Salmon P.

Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY, US. sephton@louisville.edu

            Fibromyalgia is a stress-related disorder characterized by chronic pain, memory impairment, and neuroendocrine aberrations. With the hypothesis that biological and psychological symptoms may underlie the cognitive problems, the relative influences of neuroendocrine function and psychological factors on declarative memory were examined among 50 women with fibromyalgia. This within-group analysis controlled for age, education, pain, and relevant medications. Neuroendocrine function and depression had significant independent associations with memory function. Higher log-transformed mean salivary cortisol levels were associated with better performance on both immediate and delayed visual recall and with delayed verbal recall. Depressive symptoms were negatively associated with verbal recall. These findings suggest that a basic disorder of endocrine stress responses may contribute to the cognitive symptoms experienced by fibromyalgia patients. ((c) 2003 APA, all rights reserved)







Shock-induced hyperalgesia: IV. Generality. .
Journal of Experimental Psychology: Animal Behavior Processes. 2001 Jul Vol 27(3) 219-238
Meagher, Mary W.; Ferguson, Adam R.; Crown, Eric D.; McLemore, Sherilyn; King, Tamara E.; Sieve, Amy N.; Grau, James W.

Brief-moderate shock (3, 0.75 s, 1.0 mA) has opposite effects on different measures of pain, inducing antinociception on the tail-flick test while lowering vocalization thresholds to shock and heat (hyperalgesia) and enhancing fear conditioned by a gridshock unconditioned stimulus (US). This study examined the generality of shock-induced hyperalgesia under a range of conditions and explored parallels to sensitized startle. Reduced vocalization thresholds to shock and antinociception emerged at a similar shock intensity. Severe shocks (3, 25 s, 1.0 mA or 3, 2 s, 3.0 mA) lowered vocalization threshold to shock but increased vocalization and motor thresholds to heat and undermined fear conditioned by a gridshock or a startling tone US. All shock schedules facilitated startle, but only brief-moderate shock inflated fear conditioning. The findings suggest that brief-moderate shock enhances the affective impact of aversive stimuli, whereas severe shocks attenuate pain.


Shock-induced hyperalgesia: III. Role of the bed nucleus of the stria terminalis and amygdaloid nuclei.
Behavioral Neuroscience. 2000 Jun Vol 114(3) 561-573

Crown, Eric D.; King, Tamara E.; Meagher, Mary W.; Grau, James W.

            Rats exposed to a few moderately intense (1 mA) shocks subsequently exhibit lower vocalization thresholds to shock and thermal stimuli. They also exhibit facilitated learning in a Pavlovian conditioning paradigm. Together, these results suggest that shock exposure can enhance pain (hyperalgesia). The present study examined the role of the amygdala and bed nucleus of the stria terminalis (BNST), 2 systems that have been implicated in the induction and maintenance of negative affective states. Experiment 1 showed that lesions of the central, but not the basolateral, amygdala eliminate shock-induced hyperalgesia as measured by a decrease in vocalization thresholds to shock. Experiment 2 revealed that central nucleus lesions also prevent shock-induced sensitization of the vocalization response to heat. Anterior, but not posterior, BNST lesions had a similar effect.





Neuroscience & Biobehavioral Reviews

Article in Press, Corrected Proof

Descending modulation of pain

G. F. Gebhart, 

            Although interest in descending modulation of spinal cord function dates back to the time of Sherrington, the modern era began in the late 1960s when it was shown that focal electrical stimulation in the midbrain of the rat produced analgesia sufficient to permit surgery. From this report evolved the concept of endogenous systems of pain modulation. Initial interest focused on descending inhibition of spinal nociceptive processing, but we now know that descending modulation of spinal nociceptive processing can be either inhibitory or facilitatory. As our understanding of descending facilitatory, or pro-nociceptive influences grows, so too has our appreciation of its potential importance. Accumulating evidence suggests that descending facilitatory influences may contribute to the development and maintenance of hyperalgesia and thus contribute to chronic pain states.




Neuroscience & Biobehavioral Reviews

Article in Press, Corrected Proof

Adaptations or pathologies? Long-term changes in brain and behavior after a single exposure to severe threat

Christoph P. Wiedenmayer, , a, b

a Department of Psychiatry, Columbia University College of Physicians and Surgeons, 1051 Riverside Drive, Unit 40, New York, NY 10032, USA

b Division of Developmental Psychobiology, NY State Psychiatric Institute, New York, NY 10032, USA

            The experience of a single threatening situation may alter the behavior of an animal in a long-lasting way. Long-lasting changes in behavior have been induced in laboratory animals to model and investigate the development and neural substrate of human psychopathologies. Under natural conditions, however, changes in behavior after an aversive experience may be adaptive because behavioral modifications allow animals to adjust to a threat for extended periods of time. In the laboratory setting, properties of the aversive situation and the potential of the animal to respond to the threat may be altered and lead to extensive, prolonged changes, indicating a failure in behavioral regulation. Such long-term changes seem to be mediated by neuronal alterations in components of the fear pathway. To understand psychopathologies, determinants of exaggerated responsivity and the underlying molecular and neural processes have to be analyzed in a comparative way under conditions that produce normal and abnormal fear and anxiety.



*** PAIN®, Vol. 107 (1-2) (2004) pp. 7-15

Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia

Borut Banic, Steen Petersen-Felix, Ole K. Andersen, Bogdan P. Radanov, P.M. Villiger, Lars Arendt-Nielsen and Michele Curatolo: michele.curatolo@insel.ch

            Patients with chronic pain after whiplash injury and fibromyalgia patients display exaggerated pain after sensory stimulation. Because evident tissue damage is usually lacking, this exaggerated pain perception could be explained by hyperexcitability of the central nervous system. The nociceptive withdrawal reflex (a spinal reflex) may be used to study the excitability state of spinal cord neurons. We tested the hypothesis that patients with chronic whiplash pain and fibromyalgia display facilitated withdrawal reflex and therefore spinal cord hypersensitivity. Three groups were studied: whiplash (n=27), fibromyalgia (n=22) and healthy controls (n=29). Two types of transcutaneous electrical stimulation of the sural nerve were applied: single stimulus and five repeated stimuli at 2 Hz. Electromyography was recorded from the biceps femoris muscle. The main outcome measurement was the minimum current intensity eliciting a spinal reflex (reflex threshold). Reflex thresholds were significantly lower in the whiplash compared with the control group, after both single (P=0.024) and repeated (P=0.035) stimulation. The same was observed for the fibromyalgia group, after both stimulation modalities (P=0.001 and 0.046, respectively). We provide evidence for spinal cord hyperexcitability in patients with chronic pain after whiplash injury and in fibromyalgia patients. This can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain, at least in part, pain in the absence of detectable tissue damage.




Prolotherapy Injections, Saline Injections, and Exercises for Chronic Low-Back Pain: A Randomized Trial

Michael J. Yelland, FRACGP, FAFMM, Paul P. Glasziou, PhD, FRACGP, Nikolai Bogduk, MD, DSc, Philip J. Schluter, BSc(Hons), PhD, and Mary McKernon, RN,

SPINE Volume 29, Number 1, pp 9–

            Objectives. To assess the efficacy of a prolotherapy injection and exercise protocol in the treatment of chronic nonspecific low back pain. Design. Randomized controlled trial with two-by-two factorial design, triple-blinded for injection status, and single-blinded for exercise status. Setting. General practice. Participants. One hundred ten participants with nonspecific

low-back pain of average 14 years duration were randomized to have repeated prolotherapy (20% glucose/ 0.2% lignocaine) or normal saline injections into tender lumbo-pelvic ligaments and randomized to perform either flexion/extension exercises or normal activity over 6 months. Main outcome measures: Pain intensity (VAS) and disability scores (Roland-Morris) at 2.5, 4, 6, 12, and 24 Months. Results. Follow-up was achieved in 96% at 12 months and 80% at 2 years. Ligament injections, with exercises and with normal activity, resulted in significant and sustained reductions in pain and disability throughout the trial, but no attributable effect was found for prolotherapy injections over saline injections or for exercises over normal activity. At 12 months, the proportions achieving more than 50% reduction in pain from baseline by injection group were glucose-lignocaine: 0.46 versus saline: 0.36. By activity group these proportions were exercise: 0.41 versus normal activity: 0.39. Corresponding proportions for 50% reduction in disability were glucose-lignocaine: 0.42 versus saline 0.36 and exercise: 0.36 versus normal activity: 0.38. There were no between group differences in any of the above measures. Conclusions. In chronic nonspecific low-back pain, significant and sustained reductions in pain and disability occur with ligament injections, irrespective of the solution injected or the concurrent use of exercises.



Chronic back pain and major depression in the general Canadian population

Shawn R. Currie and JianLi Wang

Pain, Volume 107, Issues 1-2 , January 2004, Pages 54-60

            Chronic pain and depression are two of the most common health problems that health professionals encounter, yet only a handful of epidemiological studies have investigated the relationship between these conditions in the general population. In the present study we examined the prevalence and correlates of major depression in persons with chronic back pain using data from the first cycle of Canadian Community Health Survey in a sample of 118,533 household residents. The prevalence of chronic back pain was estimated at 9% of persons 12 years and older. Rates of major depression, determined by the short-form of the Composite International Diagnostic Interview, were estimated at 5.9% for pain-free individuals and 19.8% for persons with chronic back pain. The rate of major depression increased in a linear fashion with greater pain severity. In logistic regression models, back pain emerged as the strongest predictor of major depression after adjusting for possible confounding factors such as demographics and medical co-morbidity. The combination of chronic back pain and major depression was associated with greater disability than either condition alone, although pain severity was found to be the strongest overall predictor of disability.



Pain, In Press, Corrected Proof

Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study,

Daniel B. Carr, Leonidas C. Goudas, William T. Denman, Daniel Brookoff, Peter S. Staats, Loralie Brennen, Geoff Green, Randi Albin, Douglas Hamilton, Mark C. Rogers et al.

            Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity 5 on a 0–10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P<0.0001), with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P=0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP.



Br J Anaesth. 2004 Feb; 92(2): 235-7.

Pain on medical wards in a district general hospital.

Dix P, Sandhar B, Murdoch J, MacIntyre PA.

            BACKGROUND: Little attention has been paid to pain on medical wards, with publications limited to the management of surgical patients. We wanted to establish the prevalence and severity of pain in the general medical setting, and how this compared with other clinical specialties. METHODS: All consenting adult in-patients were assessed daily for 5 days. Patients recorded the occurrence and severity of pain, and whether their pain was bearable. The pain team reviewed patients with unbearable pain. RESULTS: 1594 questionnaires were completed, representing 54% of the target population. 887 patients reported pain, 17% with pain scores over 6, and 10% with unbearable pain. The distribution of pain was similar for all ward types with 52% of patients on medical wards reporting pain. Of these, 20% reported severe pain and 12% unbearable pain. When patients with pain scores over 6 were analysed by consultant specialty, elderly care, general medicine, and general surgery scored highest. In each specialty 20-25% of patients with pain reported a pain score over 6. In patients reviewed by the pain team, reasons for poor analgesia included inadequate information, pain assessment, analgesic prescribing, and administration and patient reporting. CONCLUSION: Patients in all hospital specialities experience pain. Until the issue of pain management in medical patients is fully addressed the situation will not improve. Br J Anaesth 2004; 92: 235-7



Pain, In Press, Corrected Proof, Editorial

Is intranasal ketamine an appropriate treatment for chronic non-cancer breakthrough pain?

Rae F. Bell,  and Eija Kalso

            In conclusion, ketamine may be a potentially useful adjuvant to opioids for the treatment of refractory cancer pain. In this context it is usually given in low dose and as a continuous infusion. We would suggest that, until the results of long-term data are available, intranasal ketamine should be used with caution and confined to the treatment of problematic cancer-related breakthrough pain. We would contend that the use of a drug of addiction (ketamine) by a rapid-acting (intranasal) route for the treatment of chronic non-cancer pain is inappropriate and should, at least in the light of current knowledge, be avoided.



Central pain: distributed effects of focal lesions

Kenneth L. Casey

Pain, In Press, Corrected Proof, Editorial

            For now, it seems clear that we must consider the possibility that CP is caused by the combination of a focal lesion and a distributed deficit in one or more neurotransmitter or neuromodulator mechanisms. If true, this observation would put us a giant step toward an understanding of the pathophysiology of CP. We could then address the genetic, developmental, and acquired factors, including mediators of maladaptive plasticity and functional reorganization, that may put patients at risk for the development of CP and other forms of neuropathic pain.        



Adolescent chronic pain: patterns and predictors of emotional distress in adolescents with chronic pain and their parents

Christopher Eccleston, Geert Crombez, Anna Scotford, Jacqui Clinch and Hannah Connell

Pain, In Press, Corrected Proof

            Adolescents with chronic pain also report severe disability and emotional distress. A clinical sample of 80 adolescents and accompanying parents were investigated to first measure the extent of distress, and second to investigate the relationships between adolescent distress, parental distress and adolescent coping. Measures of pain intensity, anxiety, depression, disability and coping were obtained from adolescents. Parents completed measures including their own anxiety, depression and parenting stress. Overall, adolescents reported high levels of disability, depression and anxiety, and parents reported high levels of depression, anxiety and parenting stress. Multiple regression analyses revealed that the best predictors of adolescent emotional distress were the extent to which the adolescents catastrophize and seek social support to cope with the pain. There were no clear predictors of parental anxiety or depression but the specific pattern of parenting stress was best predicted by the younger age of the adolescent, the greater the chronicity of the problem, and the greater the extent of adolescent depression. These findings suggest that emotional coping is a critical variable in the distress associated with adolescent chronic pain. It is argued that adolescent emotional coping may best be understood within a relational context of seeking emotional support.



Pain, Volume 107, Issue 3, Pages 199-290 (February 2004), Editorial

Biomarkers for pain

Eija Kalso

            Various proteins can be measured in the CSF and other body fluids. They will increase our understanding of the mechanisms that underlie inflammation, nerve injury and tissue damage. These proteins can also be tested as new targets for therapeutic approaches. The pain experience, however, will remain subjective and outside the reach of a biochemistry lab. Even substance P(ain) turned out to be more complicated than what we expected. Antagonists for the receptor of substance P(ain) turned out to be potential drugs for depression, not pain!


The effects of failing to control pain: an experimental investigation

Sabine A. Janssen, Philip Spinhoven and Arnoud Arntz

Pain,Volume 107, Issue 3 (February 2004), Pages 227-233

            Chronic pain patients are often confronted with repeated failure to achieve pain relief. The aim of this study was to experimentally investigate the effects of repeated failing attempts to control pain on pain impact (pain intensity, emotional and physiological responses). Perceived control over an electrocutaneous pain stimulus was manipulated between subjects by success or failure feedback on a task by which control over pain could be acquired. In addition, success or failure at the task was manipulated without suggesting a possibility to control pain. It was hypothesized that successful control would lead to lowest pain impact, whereas failure to control pain would lead to even higher pain impact than absent control. Furthermore, it was hypothesized that failure feedback would increase pain impact when compared to success feedback. Results indicated that repeated failure to control pain increased anger and heart rate responses compared to the other conditions, but not pain intensity. It is concluded that persistent efforts to control pain in the face of failure may lead to the maintenance or exacerbation of physiological and emotional responses.



Pain. 2004 Jan; 107(1-2): 99-106.

Marital functioning, chronic pain, and psychological distress.

Cano A, Gillis M, Heinz W, Geisser M, Foran H.

            This study examined whether marital functioning variables related uniquely to psychological distress and diagnoses of depressive disorder independent of pain severity and physical disability. Participants were 110 chronic musculoskeletal pain patients. Hierarchical regression results showed that marital variables (i.e. marital satisfaction, negative spouse responses to pain) contributed significantly to depressive and anxiety symptoms over and above the effects of pain severity and physical disability. In contrast, marital variables were not significantly related to diagnoses of depressive disorder (i.e. major depression, dysthymia, or both) after controlling for pain variables. In multivariate analyses, physical disability and marital satisfaction were uniquely related to depressive symptoms whereas physical disability, pain severity, and negative spouse responses to pain were uniquely related to anxiety symptoms. Only physical disability was uniquely related to major depression. The results suggest that models of psychological distress in chronic pain patients might be enhanced by attributing greater importance to interpersonal functioning and increasing attention to anxiety.




The role of neuroticism, pain catastrophizing and pain-related fear in vigilance to pain: a structural equations approach

Liesbet Goubert, Geert Crombez and Stefaan Van Damme

Pain,Volume 107, Issue 3 (February 2004) , Pages 234-241

            The present study aimed at clarifying the precise role of pain catastrophizing, pain-related fear and personality dimensions in vigilance to pain and pain severity by means of structural equation modelling. A questionnaire survey was conducted in 122 patients with chronic or recurrent low back pain. Results revealed that pain catastrophizing and pain-related fear mediated the relationship between neuroticism and vigilance to pain. Furthermore, vigilance to pain was found to be associated with heightened pain severity. Finally, we found that neuroticism moderated the relationship between pain severity and catastrophic thinking about pain. The results strongly support the idea that vigilance to pain is dependent upon catastrophic thinking and pain-related fear. Neuroticism is best conceived of as a vulnerability factor; it lowers the threshold at which pain is perceived as threatening, and at which catastrophic thoughts about pain emerge.



Disengagement from pain: the role of catastrophic thinking about pain.

Van Damme S, Crombez G, Eccleston C.

Pain. 2004 Jan; 107(1-2): 70-6.

            This paper reports an experimental investigation of attentional engagement to and disengagement from pain. Thirty-seven pain-free volunteers performed a cueing task in which they were instructed to respond to visual target stimuli, i.e. the words 'pain' and 'tone'. Targets were preceded by pain stimuli or tone stimuli as cues. Participants were characterized as high or low pain catastrophizers, using self-reports. We found that the effect of cueing upon target detection was differential for high and low pain catastrophizers. Analyses revealed a similar amount of attentional engagement to pain in both groups. However, we also found that participants high in pain catastrophizing had difficulty disengaging from pain, whereas participants low in pain catastrophizing showed no retarded disengagement from pain. Our results provide further evidence that catastrophic thinking enhances the attentional demand of pain, particularly resulting in difficulty disengaging from pain. The clinical implications of these findings are discussed.



Pain. 2004 Jan; 107(1-2): 176-90.

Exercise and chronic low back pain: what works?

Liddle SD, Baxter GD, Gracey JH.

            The aim of this review was to investigate current evidence for the type and quality of exercise being offered to chronic low back pain (CLBP) patients, within randomised controlled trials (RCTs), and to assess how treatment outcomes are being measured. A two-fold methodological approach was adopted: a methodological assessment identified RCTs of 'medium' or 'high' methodological quality. Exercise quality was subsequently assessed according to the predominant exercise used. Outcome measures were analysed based on current recommendations. Fifty-four relevant RCTs were identified, of which 51 were scored for methodological quality. Sixteen RCTs involving 1730 patients qualified for inclusion in this review based upon their methodological quality, and chronicity of symptoms; exercise had a positive effect in all 16 trials. Twelve out of 16 programmes incorporated strengthening exercise, of which 10 maintained their positive results at follow-up. Supervision and adequate compliance were common aspects of trials. A wide variety of outcome measures were used. Outcome measures did not adequately represent the guidelines for impairment, activity and participation, and impairment measures were over-represented at the expense of others. Despite the variety offered, exercise has a positive effect on CLBP patients, and results are largely maintained at follow-up. Strengthening is a common component of exercise programmes, however, the role of exercise co-interventions must not be overlooked. More high quality trials are needed to accurately assess the role of supervision and follow-up, together with the use of more appropriate outcome measures




Correlation between pain, disability, and quality of life in patients with common low back pain.

Kovacs FM, Abraira V, Zamora J, Teresa Gil del Real M, Llobera J, Fernandez C, Bauza JR, Bauza K, Coll J, Cuadri M, Duro E, Gili J, Gestoso M, Gomez M, Gonzalez J, Ibanez P, Jover A, Lazaro P, Llinas M, Mateu C, Mufraggi N, Muriel A, Nicolau C, Olivera MA, Pascual P, Perello L, Pozo F, Revuelta T, Reyes V, Ribot S, Ripoll J, Ripoll J, Rodriguez E;   kovacs@kovacs.org

Spine. 2004 Jan 15; 29(2): 206-10.

            STUDY DESIGN: Correlation among previously validated questionnaires. OBJECTIVES: To determine the correlation between pain, disability, and quality of life in patients with low back pain. SUMMARY OF BACKGROUND DATA: The Visual Analogue Scale (VAS), and the Roland-Morris (RMQ), Oswestry (OQ), and EuroQol (EQ) Questionnaires are validated instruments to assess pain, low back pain-related disability, and quality of life. METHODS: The study was done in the primary care setting, in Mallorca, with 195 patients who visited their physician for LBP. Individuals were given the VAS, RMQ, OQ, and EQ on their first visit and 14 days later. RESULTS: Median duration of pain when entering the study was 10 days (P25,P75: 3, 40). On day 1, simple correlation was r = 0.347 between VAS and RMQ, r = -0.422 between VAS and EQ, and r = -0.442 between RMQ and EQ. On day 15, simple correlation was r = 0.570 between VAS and RMQ, r = -0.672 between VAS and EQ, and r = -0.637 between RMQ and EQ. Multiple linear regression models showed that, on day 1, the VAS score explains 12% of the RMQ score and the VAS and RMQ scores explain 27% of the EQ score. On day 15, the VAS score explains 33% of the RMQ score, and the VAS and RMQ scores explain 58% of the EQ score. On day 1, a 10% increase in VAS worsens disability by 3.3% and quality of life by 2.65%. On day 15, a 10% increase in VAS worsens disability by 4.99% and quality of life by 3.80%. Prestudy duration of pain had no influence on any model. All these correlation coefficients and models are significant at the P < 0.001 level. The OQ had lower correlation values with the other three scales, and only two of them were significant. CONCLUSION: Clinically relevant improvements in pain may lead to almost unnoticeable changes in disability and quality of life. Therefore, these variables should be assessed separately when evaluating the effect of any form of treatment for low back pain. The influence of pain and disability on quality of life progresses while they last, and doubles in 14 days. In acute and subacute patients, this increase is not dependent on the previous duration of pain.




Graded activity for low back pain in occupational health care: a randomized, controlled trial.

Staal JB, Hlobil H, Twisk JW, Smid T, Koke AJ, van Mechelen W.

Ann Intern Med. 2004 Jan 20; 140(2): 77-84.

            BACKGROUND: Low back pain is a common medical and social problem frequently associated with disability and absence from work. However, data on effective return to work after interventions for low back pain are scarce. OBJECTIVE: To determine the effectiveness of a behavior-oriented graded activity program compared with usual care. DESIGN: Randomized, controlled trial. SETTING: Occupational health services department of an airline company in the Netherlands. PATIENTS: 134 workers who were absent from work because of low back pain were randomly assigned to either graded activity (n = 67) or usual care (n = 67). INTERVENTION: Graded activity, a physical exercise program based on operant-conditioning behavioral principles, to stimulate a rapid return to work. MEASUREMENTS: Outcomes were the number of days of absence from work because of low back pain, functional status (Roland Disability Questionnaire), and severity of pain (11-point numerical scale). RESULTS: The median number of days of absence from work over 6 months of follow-up was 58 days in the graded activity group and 87 days in the usual care group. From randomization onward, graded activity was effective after 50 days of absence from work (hazard ratio, 1.9 [95% CI, 1.2 to 3.2]; P = 0.009). The graded activity group was more effective in improving functional status and pain than the usual care group. The effects, however, were small and not statistically significant. CONCLUSIONS: Graded activity was more effective than usual care in reducing the

number of days of absence from work because of low back pain.




Dose-dependent Effects of Propofol on the Central Processing of Thermal Pain.

Hofbauer RK, Fiset P, Plourde G, Backman SB, Bushnell MC.

Anesthesiology. 2004 Feb; 100(2): 386-394.

            SUMMARY: BACKGROUND Anatomic and physiologic data show that multiple regions of the forebrain are activated by pain. However, the effect of anesthetic level on nociceptive input to these regions is not well understood.METHODS The authors used positron emission tomography to measure the effect of various concentrations of propofol on pain-evoked changes in regional cerebral blood flow. Fifteen volunteers were scanned while warm and painful heat stimuli were presented to the volar forearm using a contact thermode during administration of target propofol concentrations of 0.0 microg/ml (alert control), 0.5 microg/ml (mild sedation), 1.5 microg/ml (moderate sedation), and 3.5 microg/ml (unconsciousness).RESULTS During the 0.5-microg/ml target propofol concentration (mild sedation), the subjects' pain ratings increased relative to the alert control condition; correspondingly, pain-evoked regional cerebral blood flow increased in the thalamus and the anterior cingulate cortex. In contrast, when subjects lost consciousness (3.5 microg/ml), pain-evoked responses in the thalamus and the anterior cingulate cortex were no longer observed, whereas significant pain-evoked activation remained in the insular cortex.CONCLUSION These data show that propofol has a dose-dependent effect on thalamocortical transfer of nociceptive information but that some pain-evoked cortical activity remains after loss of consciousness.






Communicative dimensions of pain catastrophizing: social cueing effects on pain behaviour and coping.

Sullivan MJ, Adams H, Sullivan ME.

Pain. 2004 Feb; 107(3): 220-6.

            The study was designed to assess whether the social context of a pain experience impacted on the relation between catastrophizing and duration of pain behaviour. Based on a communal coping model, the prediction was that the presence of an observer during a pain procedure would differentially influence the display of pain behaviour in high and low catastrophizers. University undergraduates taking part in a cold pressor procedure were randomly assigned to one of two conditions: (1) participant alone (n=30), or (2) observer present (n=34). Analysis of video records revealed that high pain catastrophizers displayed communicative pain behaviours (e.g. facial displays, vocalizations) for a longer duration when an observer was present compared to high pain catastrophizers who were alone during the pain procedure. The duration of pain management behaviours (e.g. holding, rubbing) did not vary significantly as a function of catastrophizing. When the observer was present, high catastrophizers also reported using fewer cognitive coping strategies than low catastrophizers. The pattern of findings suggests that in the presence of an observer, high pain catastrophizers show a propensity to engage in strategies that more effectively communicate their pain, and are less likely to engage in strategies that might minimize pain. Theoretical implications of the findings are discussed.



Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain

Tor D. Wager, James K. Rilling, Edward E. Smith, Alex Sokolik, Kenneth L. Casey, Richard J. Davidson, Stephen M. Kosslyn, Robert M. Rose, and Jonathan D. Cohen

Science 2004 303: 1162-1167

            The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain transmission, pain affect, or simply produce compliance with the suggestions of investigators. In two functional magnetic resonance imaging (fMRI) experiments, we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex, and was associated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.



Empathy for Pain Involves the Affective but not Sensory Components of Pain

Tania Singer, Ben Seymour, John O'Doherty, Holger Kaube, Raymond J. Dolan, and Chris D. Frith

Science 2004 303: 1157-1162

            Our ability to have an experience of another's pain is characteristic of empathy. Using functional imaging, we assessed brain activity while volunteers experienced a painful stimulus and compared it to that elicited when they observed a signal indicating that their loved one—present in the same room—was receiving a similar pain stimulus. Bilateral anterior insula (AI), rostral anterior cingulate cortex (ACC), brainstem, and cerebellum were activated when subjects received pain and also by a signal that a loved one experienced pain. AIand ACC activation correlated with individual empathy scores. Activity in the posterior insula/secondary somatosensory cortex, the sensorimotor cortex (SI/MI), and the caudal ACC was specific to receiving pain. Thus, a neural response in AIand rostral ACC, activated in common for "self" and "other" conditions, suggests that the neural substrate for empathic experience does not involve the entire "pain matrix." We conclude that only that part of the pain network associated with its affective qualities, but not its sensory qualities, mediates empathy.




Journal of Behavioral Medicine

27 (1): 91-100, February 2004

Parafunctional Clenching, Pain, and Effort in Temporomandibular Disorders

Alan G. Glaros , Eric Burton

            This study tested the hypotheses that (1) parafunctional clenching increases pain and can lead to a diagnosis of temporomandibular disorder (TMD) pain and (2) electromyographic (EMG) activity during parafunctional clenching is significantly and positively correlated with reports of pain. Fourteen individuals without TMD participated in 5 consecutive days of 20-min long EMG biofeedback training sessions of the left and right temporalis and masseter muscles. Subjects were randomly assigned to either a Decrease or Increase group and were instructed to maintain EMG activity below 2 µV or above 10 µV during training, respectively. Two Increase subjects and no Decrease subjects were diagnosed, by a blinded examiner, with TMD pain following training. Self-reported pain posttraining was significantly higher for the Increase group. Masseter EMG activity was strongly correlated with pain. Parafunctional clenching increases pain and can lead to a diagnosis of TMD in otherwise pain-free individuals. Pain reports are positively correlated with the activity of the masseter muscle.



Journal of Behavioral Medicine

27 (1): 77-89, February 2004

Pain-Related Anxiety in the Prediction of Chronic Low-Back Pain Distress

Kevin E. Vowles, Michael J. Zvolensky, Richard T. Gross, Jeannie A. Sperry; kvowles@mix.wvu.edu

            This study evaluated the relation of particular aspects of pain-related anxiety to characteristics of chronic pain distress in a sample of 76 individuals with low-back pain. Consistent with contemporary cognitive–behavioral models of chronic pain, the cognitive dimension of the Pain Anxiety Symptoms Scale (PASS; McCracken, Zayfert, and Gross, 1992, Pain 50: 67–73) was uniquely predictive of cognitive-affective aspects of chronic pain, including affective distress, perceived lack of control, and pain severity. In contrast, the escape and avoidance dimension of the PASS was more predictive of behavioral interference in life activities. Overall, the findings are discussed within the context of identifying particular pain-related anxiety mechanisms contributing to differential aspects of pain-related distress and clinical impairment.




Occupational Medicine 2004;54:3-13

Low back pain interventions at the workplace: a systematic literature review

Torill H. Tveito, Mari Hysing and Hege R. Eriksen

            Objective To assess the effect of controlled workplace interventions on low back pain (LBP) through a review of controlled studies. The rising costs of employees with LBP have resulted in an abundance of offers to society and organizations of interventions to prevent and/or treat the problem. Little is known of the effect of the different interventions.  Methods A systematic literature search based on the inclusion criteria: controlled trial, work setting and assessment of at least one of the four main outcome measures: sick leave; costs; new episodes of LBP; and pain. Effect of the interventions was reported for the four main outcome measures.  Results Thirty-one publications from 28 interventions were found to comply with the inclusion criteria. Exercise interventions to prevent LBP among employees and interventions to treat employees with LBP have documented an effect on sick leave, costs and new episodes of LBP. Multidisciplinary interventions have documented an effect on the level of pain.  Conclusions The results show that there is good reason to be careful when considering interventions aiming to prevent LBP among employees. Of all the workplace interventions only exercise and the comprehensive multidisciplinary and treatment interventions have a documented effect on LBP. There is a need for studies employing good methodology.



The Spine Journal, Article in Press

Efficacy of spinal manipulation and mobilization for low back pain and neck pain: a systematic review and best evidence synthesis

Gert Bronfort PhD, DC, Mitchell Haas DC, MA, Roni L. Evans DC, MS and Lex M. Bouter PhD     Background context: Despite the many published randomized clinical trials (RCTs), a substantial number of reviews and several national clinical guidelines, much controversy still remains regarding the evidence for or against efficacy of spinal manipulation for low back pain and neck pain.

Purpose: To reassess the efficacy of spinal manipulative therapy (SMT) and mobilization (MOB) for the management of low back pain (LBP) and neck pain (NP), with special attention to applying more stringent criteria for study admissibility into evidence and for isolating the effect of SMT and/or MOB.

Study design: RCTs including 10 or more subjects per group receiving SMT or MOB and using patient-oriented primary outcome measures (eg, patient-rated pain, disability, global improvement and recovery time).

Methods: Articles in English, Danish, Swedish, Norwegian and Dutch reporting on randomized trials were identified by a comprehensive search of computerized and bibliographic literature databases up to the middle of 2002. Two reviewers independently abstracted data and assessed study quality according to eight explicit criteria. A best evidence synthesis incorporating explicit, detailed information about outcome measures and interventions was used to evaluate treatment efficacy. The strength of evidence was assessed by a classification system that incorporated study validity and statistical significance of study results. Sixty-nine RCTs met the study selection criteria and were reviewed and assigned validity scores varying from 6 to 81 on a scale of 0 to 100. Forty-three RCTs met the admissibility criteria for evidence.


Acute LBP: There is moderate evidence that SMT provides more short-term pain relief than MOB and detuned diathermy, and limited evidence of faster recovery than a commonly used physical therapy treatment strategy.

Chronic LBP: There is moderate evidence that SMT has an effect similar to an efficacious prescription nonsteroidal anti-inflammatory drug and that SMT/MOB is effective at least in the short term when compared with placebo and general practitioner care. There is limited to moderate evidence that SMT is better than physical therapy and home back exercise in both the short and long term. There is limited evidence that SMT is as good or better than chemonucleolysis for disc herniation in the short and long term. However, there is also limited evidence that MOB is inferior to back exercise after disc herniation surgery.

Mix of acute and chronic LBP:/MOB provides either similar or better pain outcomes in the short and long term when compared with placebo and with other treatments, such as McKenzie therapy, medical care, management by physical therapists, soft tissue treatment and back school.

Acute NP: There are few studies, and the evidence is currently inconclusive.

Chronic NP: There is moderate evidence that SMT/MOB is superior to general practitioner management for short-term pain reduction but that SMT offers less pain relief in the long term than high-technology rehabilitative exercise. There is limited evidence that SMT, in both the short and long term, has a similar effect to low technology exercise and to physical therapy.

Mix of acute and chronic NP. The overall evidence is not clear. There is moderate evidence that MOB is superior to physical therapy and family physician care, and similar to SMT in both the short and long term. There is limited evidence that SMT, in both the short and long term, is inferior to physical therapy.

Conclusions: Our data synthesis suggests that recommendations can be made with some confidence regarding the use of SMT and/or MOB as a viable option for the treatment of both low back pain and NP. There have been few high-quality trials distinguishing between acute and chronic patients, and most are limited to shorter-term follow-up. Future trials should examine well-defined subgroups of patients, further address the value of SMT and MOB for acute patients, establish optimal number of treatment visits and consider the cost-effectiveness of care.



The Spine Journal, Article in Press

The influence of intense exercise-based physical therapy program on back pain anticipated before and induced by physical activities

James Rainville MD, Carol Hartigan MD, Cristin Jouve MD and Eugenio Martinez MD

            Background context: Pain anticipated before and induced by physical activities has been shown to influence the physical performance of patients with chronic back pain. Limited data exist as to the influence of treatment on this component of pain. Purpose: This study attempted to determine if pain anticipated before and induced by physical activities was altered during an exercise-oriented physical therapy program for chronic back pain. bStudy design/setting: Subjects were recruited from three physical therapy sites with similar spine rehabilitation programs that used intense exercise delivered in a group format. During the recruitment period, 70 subjects with chronic low back pain and disability agreed to participate and complied with recommended treatments. The primary outcome measures were anticipated and induced pain as assessed by visual analog scales (VAS) during six tests of back flexibility and strength. Additional outcome measures included the performance levels of these six tests (trunk flexion, extension, straight leg raising, back strength, lifting from floor to waist and waist to shoulder height), global back and leg VAS and Oswestry Low Back Pain Disability Questionnaire scores. Methods: At evaluation for the spine rehabilitation programs, we recorded the anticipated and induced pain levels associated with the six tests of back function, the performance levels on each test and global pain and disability scores. Subjects then participated in the spine rehabilitation program that consisted of intense exercise delivered up to three times per week, for 2 hours over a period of 6 weeks. All outcome measures were reassessed at discharge. Pre- and posttreatment outcome scores were statistically compared using paired sample t tests and chi-squared test. Spearman correlation coefficients were used to compare anticipated and induced pain results with global back and leg pain VAS scores, Oswestry scores and physical performance levels for each physical test. Results: Most measures of anticipated and induced pain improved between evaluation and discharge. Improvements were noted for global back pain (p<.001), leg pain (p=.001), disability (p<.001) and performance on each physical testing (p<.001) after treatment. Performances on all physical testing correlated with anticipated and induced pain for all tests at evaluation but only for measures of flexibility at discharge. Improvements in global pain and disability correlated with improvements in anticipated and induced pain with physical testing.

Conclusion: Anticipated and induced pain with physical activities was lessened after physical therapy using exercise. Anticipated and induced pain with physical activities related to physical performance levels, global pain and disability ratings. These findings may help explain how exercise exerts a positive influence on chronic back pain and disability.



The Spine Journal

Volume 4, Issue 1 , 2 January 2004, Pages 106-115

Exercise as a treatment for chronic low back pain

James Rainville MD, Carol Hartigan MD, Eugenio Martinez MD, Janet Limke MD, Cristin Jouve MD and Mark Finno MD

            Background context: Exercise is a widely prescribed treatment for chronic low back pain, with demonstrated effectiveness for improving function and work. Purpose: The goal of this article is to review several key aspects about the safety and efficacy of exercise that may help clinicians understand its utility in treating chronic back pain. Study design/setting: A computerized literature search of MEDLINE was conducted using "exercise," "fitness," "back pain," "backache" and "rehabilitation" as search words. Identified abstracts were scanned, and useful articles were acquired for further review. Additional references were acquired through the personal collections of research papers possessed by the authors and by reviewing prior review articles on this subject. These final papers were scrutinized for data relevant to the key aspects about exercise covered in this article. Results: For people with acute, subacute or chronic low back pain, there is no evidence that exercise increases the risk of additional back problems or work disability. To the contrary, current medical literature suggests that exercise has either a neutral effect or may slightly reduce risk of future back injuries. Exercise can be prescribed for patients with chronic low back pain with three distinct goals. The first and most obvious goal is to improve or eliminate impairments in back flexibility and strength, and improve performance of endurance activities. There is a large body of evidence confirming that this goal can be accomplished for a majority of patients with chronic low back pain. The second goal of exercise is to reduce the intensity of back pain. Most studies of exercise have noted overall reduction in back pain intensity that ranges from 10% to 50% after exercise treatment. The third goal of exercise is to reduce back pain–related disability through a process of desensitization of fears and concerns, altering pain attitudes and beliefs and improving affect. The mechanisms through which exercise can accomplish this goal have been the subject of substantial research. Conclusions: Exercise is safe for individuals with back pain, because it does not increase the risk of future back injuries or work absence. Substantial evidence exists supporting the use of exercise as a therapeutic tool to improve impairments in back flexibility and strength. Most studies have observed improvements in global pain ratings after exercise programs, and many have observed that exercise can lessen the behavioral, cognitive, affect and disability aspects of back pain syndromes.



The Spine Journal

Volume 3, Issue 6 , November-December 2003, Pages 435-441

Neck and shoulder pain in 70- to 79-year-old men and women: findings from the Health, Aging and Body Composition Study

Molly T. Vogt PhD,, Eleanor M. Simonsick PhD, Tamara B. Harris MD, Michael C. Nevitt PhD, James D. Kang MD, Susan M. Rubin MPH, Stephen B. Kritchevsky PhD and Anne B. Newman MD, MPH

            Background context: Musculoskeletal pain in the cervicobrachial region is considered a major health problem among adults of working age, but little is known about the impact of this pain in the elderly.

Purpose: Determine the prevalence of neck and shoulder pain in a well-functioning cohort, identify factors associated with this pain, assess the pattern of coexisting joint pain and evaluate the impact of this pain on physical functioning. Study design: Cross-sectional study. Patient sample: Black and white men and women, aged 70 to 79 years, participating in the Health, Aging and Body Composition (Health ABC) study. Methods: Between April 1997 and June 1998, 3,075 men and women participating in Health ABC study completed the initial home interview and clinical examination. Information was collected on musculoskeletal pain, medical history, depressive symptomatology and physical function. Physical performance measures were obtained. Results: A total of 11.9% of participants reported neck pain of one month or more in duration and 18.9% reported shoulder pain. White women had the highest prevalence of neck pain (15.4%) and black women the highest prevalence of shoulder pain (24.3%). The correlates of both neck and shoulder pain were female gender, no education beyond high school, poorer self-rated health, depressive symptomatology and a medical history of arthritis, heart attack, angina. Increasing severity of both neck and shoulder pain was associated with an increased prevalence of joint pain at other body sites and with poor functional capacity. Measures of physical performance involving the upper extremity were also decreased. Conclusions: Neck and shoulder pain, either alone or in conjunction with pain in other joints, has a substantial impact on the function and well-being of the older adults in this cohort.



Back and Neck Pain Exhibit Many Common Features in Old Age: A Population-Based Study of 4,486 Danish Twins 70-102 Years of Age.

Spine. 29(5):576-580, March 1, 2004.

Hartvigsen, Jan DC, PhD *; Christensen, Kaare MD, PhD +; Frederiksen, Henrik MD, PhD +

Study Design. Cross-sectional and longitudinal analysis of data comprising 4486 Danish twins 70-102 years of age. Objectives. To describe the 1-month prevalence of back pain, neck pain, and concurrent back and neck pain and the development of these over time, associations with other health problems, education, smoking, and physical, and mental functioning. Summary of Background Data. Back pain and neck pain are prevalent symptoms in the population; however, there is little research addressing these conditions in older age groups. Methods. Extensive interview data on health, lifestyle, social, and educational factors were collected in a nationwide cohort-sequential study of 70+-year-old Danish twins. Data for back pain, neck pain, lifetime prevalence of a comprehensive list of diseases, education, and self-rated health were based on self-report. Physical and mental functioning were measured using validated performance tests. Data including associated factors were analyzed in a cross-sectional analysis for answers given at entry into the study, and longitudinal analysis was performed for participants in all four surveys. Results. The overall 1-month prevalence for back pain only was 15%, for neck pain only 11%, and for concurrent back and neck pain 11%. The prevalence varied negligibly over time and between the age groups, and 63% of participants in all surveys had no episodes or only one episode of back or neck pain. Back pain and neck pain were associated with a number of other diseases and with poorer self-rated health. Back and neck pain sufferers had significantly lower scores on physical but not cognitive functioning.  Conclusions. Back pain and neck pain are common, intermittent symptoms in old age. Back pain and neck pain are associated with general poor physical health in old age.



The Spine Journal

Volume 3, Issue 6 , November-December 2003, Pages 460-465

Correlation of clinical examination characteristics with three sources of chronic low back pain

Sharon Young PT, Cert. MDT, Charles Aprill MD and Mark Laslett PT, Dip. MT, Dip. MDT           

            Background context:Research has demonstrated some progress in using a clinical examination to predict discogenic or sacroiliac (SI) joint sources of pain. No clear predictors of symptomatic lumbar zygapophysial joints have yet been demonstrated. Purpose: To identify significant components of a clinical examination that are associated with symptomatic lumbar discs, zygapophysial joints and SI joints. Study design: A prospective, criterion-related concurrent validity study performed at a private radiology practice specializing in spinal diagnostics. Patient sample:The sample consisted of 81 patients with chronic lumbopelvic pain referred for diagnostic injections. Outcome measures: Contingency tables were constructed for nine features of the clinical evaluation compared with the results of diagnostic injections. Statistical analysis included chi-squared test for independence, phi and odds ratios with confidence intervals. Method: Patients received blinded clinical examinations by physical therapists, and diagnostic injections were used as the criterion standard. Results: Significant relationships were found between discogenic pain and centralization of pain during repeated movement testing, and pain when rising from sitting. Lumbar zygapophysial joint pain was associated with absence of pain when rising from sitting. Sacroiliac joint pain was related to three or more positive pain provocation tests, pain when rising from sitting, unilateral pain and absence of lumbar pain. Conclusions: Significant correlations exist between clinical examination findings and symptomatic lumbar discs, zygapophysial and SI joints. The strongest relationships were seen between SI joint pain and three or more positive pain provocation tests, centralization of pain for symptomatic discs and absence of pain when rising from sitting for symptomatic lumbar zygapophysial joints.



The Spine Journal

Volume 3, Issue 5 , September-October 2003, Pages 400-403

Failed back surgery: etiology and diagnostic evaluation

Jerome Schofferman MD, James Reynolds MD, Richard Herzog MD, Edward Covington MD, Paul Dreyfuss MD and Conor O'Neill MD

            BACKGROUND CONTEXT: This is a synopsis of a symposium presented to the North American Spine Society Annual Meeting in Montreal, Canada, 2002. PURPOSE: To provide the reader with a distillation of the material presented regarding the diagnosis of failed back surgery syndrome (FBSS). METHODS: Panel presentation. RESULTS: The proper treatment of patients with FBSS depends on a precise and accurate diagnosis. With a careful history, examination, imaging studies, psychological evaluation and diagnostic injections, a diagnosis can be reached in over 90% of patients. The most common diagnoses are foraminal stenosis (25% to 29%), painful disc (20% to 22%), pseudarthrosis (14%), neuropathic pain (10%), recurrent disc herniation (7% to 12%), facet joint pain (3%) and sacroiliac joint (SIJ) pain (2%). Psychological factors are always present and may help or hinder. Common psychological diagnoses include depression, anxiety disorder and substance abuse disorder. Diagnostic injections are very useful for facet joint pain, SIJ pain and discogenic pain; they may also be used to confirm a putative neural compression as a cause of pain. CONCLUSIONS: Spine surgeons must be aware of the common causes of FBSS in order to be able to thoroughly evaluate their patients and to minimize the occurrence of this problem.




Pain Med. 2003 Jun;4(2):141-81.

A structured evidence-based review on the meaning of nonorganic physical signs: Waddell signs.

Fishbain DA, Cole B, Cutler RB, Lewis J, Rosomoff HL, Rosomoff RS.

Department of Psychiatry, University of Miami School of Medicine, Miami, Florida, USA. d.fishbain@miami.edu.

               STUDY DESIGN: This is a structured, evidence-based review of all available studies addressing the concept of nonorganic findings: Waddell signs (WSs). OBJECTIVES: To determine what evidence, if any, exists for the various interpretations for the presence of WSs on physical examination. SUMMARY OF BACKGROUND DATA: WSs are a group of eight physical findings divided into five categories, the presence of which has been alleged at times to have the following interpretations: Malingering/secondary gain, hysteria, psychological distress, magnified presentation, abnormal illness behavior, abnormal pain behavior, and somatic amplification. At the present time, there is, therefore, significant confusion as to what these findings mean. METHODS: A computer and manual literature search produced 61 studies and case series reports relating to WSs. These references were reviewed in detail, sorted, and placed into tabular form according to the following subject areas: 1) Reliability (test-retest); 2) Reliability (inter-rater); 3) Reliability (factor analysis); 4) Validity, psychological distress; 5) Validity, correlation Minnesota Multiphasic Pain Inventory (MMPI); 6) Validity, correlation abnormal illness behavior; 7) Validity, other behaviors; 8) Validity, as a nonorganic phenomenon; 9) Validity, correlation pain drawing; 10) Validity, functional performance; 11) Validity, treatment outcome; 12) Validity, predicting surgical treatment outcome; 13) Validity, return to work outcome; 14) Validity, secondary gain correlation; and 15) Validity, pain correlation. Each study in each topic area was classified according to the type of study it represented according to the type of evidence guidelines developed by the Agency for Health Care Policy and Research (AHCPR). In addition, a list of 14 study quality criteria was used to measure the quality of each study. Each study was categorized for each criterion as positive, (criterion filled), negative (criterion not filled), or not applicable independently by two of the authors. A percent quality score was obtained for each study by counting the total number of positives obtained, dividing by 14 minus the total number of not applicables, and multiplying by 100. Only studies having a quality score of 75% or greater were used to formulate the conclusions of this review. The strength and consistency of the evidence represented by the remaining studies in each topic area (above) was then categorized according to the strength and consistency AHCPR guidelines. Conclusions of this review for each topic area are based on these results. RESULTS OF DATA SYNTHESIS: Of the 61 studies, four had quality scores below 75% and were not used to generate the results of this review. According to the AHCPR guidelines for strength and consistency of the reviewed data, the following results were obtained: 1) There was consistent evidence for WSs being associated with decreased functional performance, poor nonsurgical treatment outcome, and greater levels of pain; 2) There was generally consistent evidence for WSs not being associated with psychological distress, abnormal illness behavior, or secondary gain; 3) There was also generally consistent evidence that WSs are an organic phenomenon and that they cannot be used to discriminate organic from nonorganic problems; 4) There was inconsistent evidence that WSs do demonstrate inter-rater reliability, do not correlate with the neurotic triad of the MMPI, are associated with poorer surgical treatment outcome, and are associated with nonreturn to work; 5) There was little or no evidence that WSs demonstrate test-retest reliability, or reliable factors, and are associated with self-esteem problems, catastrophizing, or the nonorganic pain drawing. CONCLUSIONS: Based on the above results, the following conclusions were made: 1) WSs do not correlate with psychological distress; 2) WSs do not discriminate organic from nonorganic problems; 3) WSs may represent an organic phenomenon; 4) WSs are associated with poorer treatment outcome; 5) WSs are associated with greater pain levels; 6) WSs are not associated with secondary gain; and 7) As a group, WS studies demonstrate some methodological problems.



Facet Joint Kinematics and Injury Mechanisms During Simulated Whiplash.

Pearson, Adam M. BA; Ivancic, Paul C. MPhil; Ito, Shigeki MD; Panjabi, Manohar M. PhD

Spine. 29(4):390-397, February 15, 2004.

            Study Design. Facet joint kinematics and capsular ligament strains were evaluated during simulated whiplash of whole cervical spine specimens with muscle force replication. Objectives. To describe facet joint kinematics, including facet joint compression and facet joint sliding, and quantify peak capsular ligament strain during simulated whiplash. Summary of Background Data. Clinical studies have implicated the facet joint as a source of chronic neck pain in whiplash patients. Prior in vivo and in vitro biomechanical studies have evaluated facet joint compression and excessive capsular ligament strain as potential injury mechanisms. No study has comprehensively evaluated facet joint compression, facet joint sliding, and capsular ligament strain at all cervical levels during multiple whiplash simulation accelerations. Methods. The whole cervical spine specimens with muscle force replication model and a bench-top trauma sled were used in an incremental trauma protocol to simulate whiplash of increasing severity. Peak facet joint compression (displacement of the upper facet surface towards the lower facet surface), facet joint sliding (displacement of the upper facet surface along the lower facet surface), and capsular ligament strains were calculated and compared to the physiologic limits determined during intact flexibility testing. Results. Peak facet joint compression was greatest at C4-C5, reaching a maximum of 2.6 mm during the 5 g simulation. Increases over physiologic limits (P < 0.05) were initially observed during the 3.5 g simulation. In general, peak facet joint sliding and capsular ligament strains were largest in the lower cervical spine and increased with impact acceleration. Capsular ligament strain reached a maximum of 39.9% at C6-C7 during the 8 g simulation. Conclusions. Facet joint components may be at risk for injury due to facet joint compression during rear-impact accelerations of 3.5 g and above. Capsular ligaments are at risk for injury at higher accelerations.





Sterling, Michele PhD; Jull, Gwendolen PhD; Vicenzino, Bill PhD; Kenardy, Justin PhD

Characterization of Acute Whiplash-Associated Disorders.

Spine. 29(2):182-188, January 15, 2004.

            Study Design. An experimental study of motor and sensory function and psychological distress in subjects with acute whiplash injury. Objectives. To characterize acute whiplash injury in terms of motor and sensory systems dysfunction and psychological distress and to compare subjects with higher and lesser levels of pain and disability. Summary of Background Data. Motor system dysfunction, sensory hypersensitivity, and psychological distress are present in chronic whiplash associated disorders (WAD), but little is known of such factors in the acute stage of injury. As higher levels of pain and disability in acute WAD are accepted as signs of poor outcome, further characterization of this group from those with lesser symptoms is important. Materials and Methods. Motor function (cervical range of movement [ROM], joint position error [JPE]; activity of the superficial neck flexors [EMG] during a test of cranio-cervical flexion), quantitative sensory testing (pressure, thermal pain thresholds, and responses to the brachial plexus provocation test), and psychological distress (GHQ-28, TAMPA, IES) were measured in 80 whiplash subjects (WAD II or III) within 1 month of injury, as were 20 control subjects. Results. Three subgroups were identified in the cohort using cluster analysis based on the Neck Disability Index: those with mild, moderate, or severe pain and disability. All whiplash groups demonstrated decreased ROM and increased EMG compared with the controls (all P < 0.01). Only the moderate and severe groups demonstrated greater JPE and generalized hypersensitivity to all sensory tests (all P < 0.01). The three whiplash subgroups demonstrated evidence of psychological distress, although this was greater in the moderate and severe groups. Measures of psychological distress did not impact on between group differences in motor or sensory tests. Conclusions. Acute whiplash subjects with higher levels of pain and disability were distinguished by sensory hypersensitivity to a variety of stimuli, suggestive of central nervous system sensitization occurring soon after injury. These responses occurred independently of psychological distress. These findings may be important for the differential diagnosis of acute whiplash injury and could be one reason why those with higher initial pain and disability demonstrate a poorer outcome.





Correlation Between Pain, Disability, and Quality of Life in Patients With Common Low Back Pain.

Spine. 29(2):206-210, January 15, 2004.

Kovacs, Francisco M. MD, PhD; Abraira, Victor PhD; Zamora, Javier PhD; Teresa Gil del Real, Maria MPH; Llobera, Joan MD, MPH; Fernandez, Carmen MD [S];

            Study Design. Correlation among previously validated questionnaires. Objectives. To determine the correlation between pain, disability, and quality of life in patients with low back pain. Summary of Background Data. The Visual Analogue Scale (VAS), and the Roland-Morris (RMQ), Oswestry (OQ), and EuroQol (EQ) Questionnaires are validated instruments to assess pain, low back pain-related disability, and quality of life. Methods. The study was done in the primary care setting, in Mallorca, with 195 patients who visited their physician for LBP. Individuals were given the VAS, RMQ, OQ, and EQ on their first visit and 14 days later. Results. Median duration of pain when entering the study was 10 days (P25,P75: 3, 40). On day 1, simple correlation was r = 0.347 between VAS and RMQ, r = -0.422 between VAS and EQ, and r = -0.442 between RMQ and EQ. On day 15, simple correlation was r = 0.570 between VAS and RMQ, r = -0.672 between VAS and EQ, and r = -0.637 between RMQ and EQ. Multiple linear regression models showed that, on day 1, the VAS score explains 12% of the RMQ score and the VAS and RMQ scores explain 27% of the EQ score. On day 15, the VAS score explains 33% of the RMQ score, and the VAS and RMQ scores explain 58% of the EQ score. On day 1, a 10% increase in VAS worsens disability by 3.3% and quality of life by 2.65%. On day 15, a 10% increase in VAS worsens disability by 4.99% and quality of life by 3.80%. Prestudy duration of pain had no influence on any model. All these correlation coefficients and models are significant at the P < 0.001 level. The OQ had lower correlation values with the other three scales, and only two of them were significant. Conclusion. Clinically relevant improvements in pain may lead to almost unnoticeable changes in disability and quality of life. Therefore, these variables should be assessed separately when evaluating the effect of any form of treatment for low back pain. The influence of pain and disability on quality of life progresses while they last, and doubles in 14 days. In acute and subacute patients, this increase is not dependent on the previous duration of pain.





Pain, In Press

Development and validation of the Neuropathic Pain Symptom Inventory

Didier Bouhassira, Nadine Attal, Jacques Fermanian, Haiel Alchaar, Michèle Gautron, Etienne Masquelier, Sylvie Rostaing, Michel Lanteri-Minet, Elisabeth Collin, Jacques Grisart and François Boureau

            This study describes the development and validation of the Neuropathic Pain Symptom Inventory (NPSI), a new self-questionnaire specifically designed to evaluate the different symptoms of neuropathic pain. Following a development phase and a pilot study, we generated a list of descriptors reflecting spontaneous ongoing or paroxysmal pain, evoked pain (i.e. mechanical and thermal allodynia/hyperalgesia) and dysesthesia/paresthesia. Each of these items was quantified on a (0–10) numerical scale. The validation procedure was performed in 176 consecutive patients with neuropathic pain of peripheral (n=120) or central (n=56) origin, recruited in five pain centers in France and Belgium. It included: (i) assessment of the test–retest reliability of each item, (ii) determination of the factorial structure of the questionnaire and analysis of convergent and divergent validities (i.e. construct validity), and (iii) evaluation of the ability of the NPSI to detect the effects of treatment (i.e. sensitivity to change). The final version of the NPSI includes 10 descriptors (plus two temporal items) that allow discrimination and quantification of five distinct clinically relevant dimensions of neuropathic pain syndromes and that are sensitive to treatment. The psychometric properties of the NPSI suggest that it might be used to characterize subgroups of neuropathic pain patients and verify whether they respond differentially to various pharmacological agents or other therapeutic interventions.




Pain, In Press

Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial

G. L. Moseley 

            Complex regional pain syndrome type 1 (CRPS1) involves cortical abnormalities similar to those observed in phantom pain and after stroke. In those groups, treatment is aimed at activation of cortical networks that subserve the affected limb, for example mirror therapy. However, mirror therapy is not effective for chronic CRPS1, possibly because movement of the limb evokes intolerable pain. It was hypothesised that preceding mirror therapy with activation of cortical networks without limb movement would reduce pain and swelling in patients with chronic CRPS1. Thirteen chronic CRPS1 patients were randomly allocated to a motor imagery program (MIP) or to ongoing management. The MIP consisted of two weeks each of a hand laterality recognition task, imagined hand movements and mirror therapy. After 12 weeks, the control group was crossed-over to MIP. There was a main effect of treatment group (F(1,11)=57, P<0.01) and an effect size of ~25 points on the Neuropathic pain scale. The number needed to treat for a 50% reduction in NPS score was ~2. The effect of treatment was replicated in the crossed-over control subjects. The results uphold the hypothesis that a MIP initially not involving limb movement is effective for CRPS1 and support the involvement of cortical abnormalities in the development of this disorder. Although the mechanisms of effect of the MIP are not clear, possible explanations are sequential activation of cortical pre-motor and motor networks, or sustained and focussed attention on the affected limb, or both.




Pain, Article in Press

Lowering fear-avoidance and enhancing function through exposure in vivo:

A multiple baseline study across six patients with back pain

Katja Boersma, Steven Lintona, Thomas Overmeer, Markus Jansson, Johan Vlaeyen and Jeroen de Jong

            This study investigated the effects of an exposure in vivo treatment for chronic pain patients with high levels of fear and avoidance. The fear-avoidance model offers an enticing explanation of why some back pain patients develop persistent disability, stressing the role of catastrophic interpretations; largely fueled by beliefs and expectations that activity will cause injury and will worsen the pain problem. Recently, an exposure in vivo treatment was developed that aims to enhance function by directly addressing these fears and expectations.

            The purpose of this study was to describe the short-term, consequent effect of an exposure in vivo treatment. The study employed a multiple baseline design with six patients who were selected based on their high levels of fear and avoidance.

            The results demonstrated clear decreases in rated fear and avoidance beliefs while function increased substantially. These improvements were observed even though rated pain intensity actually decreased somewhat. Thus, the results replicate and extend the findings of previous studies to a new setting, with other therapists and a new research design. These results, together with the initial studies, provide a basis for pursuing and further developing the exposure technique and to test it in group designs with larger samples.



Pain, Article in Press

Possible association of interleukin 1 gene locus polymorphisms with low back pain

S. Solovieva, P. Leino-Arjasa, J. Saarelab, K. Luomaa, R. Raininkod and H. Riihimäki

            Based on a hypothesis that interleukin 1 (IL-1) activity is associated with low back pain (LBP), we investigated relationships between previously described functional IL-1 gene polymorphisms and LBP. The subjects were a subgroup of a Finnish study cohort. The IL-1(C889–T), IL-1(C3954–T) and IL-1 receptor antagonist (IL-1RN)(G1812–A, G1887–C and T11100–C) polymorphisms were genotyped in 131 middle-aged men from three occupational groups (machine drivers, carpenters and office workers). A questionnaire inquired about individual and lifestyle characteristics and the occurrence of LBP, the number of days with pain and days with limitation of daily activities because of pain, and pain intensity, during the past 12 months. Lumbar disc degeneration was determined with magnetic resonance imaging. Carriers of the IL-1RNA1812 allele had an increased risk of LBP (OR 2.5, 95% CI 1.0–6.0) and carriers of this allele in combination with the IL-1T889 or IL-1T3954 allele had a higher risk of and more days with LBP than non-carriers. Pain intensity was associated with the simultaneous carriage of the IL-1T889 and IL-1RNA1812 alleles (OR 3.7, 95% CI 1.2–11.9). Multiple regression analyses allowing for occupation and disc degeneration showed that carriage of the IL-1RNA1812 allele was associated with the occurrence of pain, the number of days with pain and days with limitations of daily activities. Carriage of the IL-1T3954 allele was associated with the number of days with pain. The results suggest a possible contribution of the IL-1 gene locus polymorphisms to the pathogenesis of LBP. The possibility of chance findings cannot be excluded due to the small sample size.



Pain, Article in Press

Evidence for heritability of pain in patients with traumatic neuropathy

Marshall Devor 

            ...convincing data in animals for heritable pre-disposition to developing chronic pain after nerve injury...humans, however, it is inherently difficult to document a genetic contribution....

Tentative evidence of heritability can come from observing whether multiple nerve injures in individual patients are consistently associated with chronic pain, or the absence of pain...a recent report on traumatic double amputees in Sierra Leone showed a very high bilateral concordance for stump and phantom limb pain...in only a fraction of patients. But when they occurred in one arm, they almost always occurred also in the other...another example...published recently in Pain, support an inference of intrinsic individual predisposition to neuropathic pain....prevalence of neuropathic pain lasting at least 6 months in patients who underwent coronary artery bypass graft (CABG) surgery...cause some nerve trauma...sternotomy...saphenectomy, etc. ...authors reported chronic pain secondary to the chest surgery in 12% of 1080 patients, chronic leg pain secondary to the saphenectomy in 9.3%, and chronic pain at both locations in 18% for a grand total of chronic pain in 39.3%. The use of pain descriptors (words) associated with neuropathy was frequent, and pain had a considerable impact on quality-of-life measures...reemphasize the risk of chronic pain due to iatrogenic nerve injury during surgery...frequently missed...results also deliver a second message not noted by the authors. If the chances of developing pain at each site were independent, and related only to the vagarities of the surgical procedure itself, and these chances are 0.12 for chest pain and 0.09 for leg pain, then the odds of getting pain at both sites would be only 0.12×0.09=0.01 (1.1%). In fact...pain at both sites occurred much more often, in 18% of patients (P<0.001, 2)...more conservative calculation =8.1% (P<0.001, 2). ...data herefore constitute evidence that certain patients are pre-disposed to developing chronic pain after nerve injury....The individual pre-disposition to chronic neuropathic pain suggested by these data may well reflect genetic control of the processes that underlie the pain. As noted above, recent animal studies have provided strong evidence of a considerable degree of heritability in neuropathic pain phenotype. Nonetheless, certain caveats... in addition to genes, individual pre-dispositions may also have roots in socialization and other environmental factors. For example, pain at one site may induce in the individual global `hypervigilance' to similar symptoms elsewhere. Likewise, it is possible that despite attention to uniform technique, that subtle differences among surgical teams contributed to the high concordance of pain at the two sites.




Pain, Article in Press

Development of and recovery from long-term pain. A 6-year follow-up study of a cross-section of the adult Danish population

Jørgen Eriksen, Ola Ekholm, Per Sjøgren and Niels K. Rasmussen

            A 6-year follow-up study of a cross-section of the adult Danish population, based on data from the Danish Health and Morbidity Surveys in 1994 and 2000 is presented. The pain populations were identified through the pain intensity verbal rating scale (VRS) included in the Short Form 36. The 2000 survey also included a question on duration of pain (>6 months). Using this as the `gold standard', a validation study was performed, which identified the highest accuracy (85%) at the VRS cut-off level: no pain, very mild, or mild pain (control group) versus moderate, severe, or very severe pain (pain group). The cohort comprised 2649 individuals, representative of the Danish population. Prevalence rates of pain in 1994 and 2000 were 13.5 and 15.7%, respectively. The cumulated 6-year incidence of pain development was 10.7%, and the cumulated incidence of pain recovery was 52.1%. During the investigated period, 9.2% of individuals moved from a `no pain status' to a `pain status', 7% moved from a `pain status' to a `no pain status', and 6.5% maintained their `pain status'. Significant risk factors for pain development were female gender [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.2–2.0], short education (OR 1.5, CI 1.0–2.2), poor self-rated health (OR 3.3, CI 2.4–4.7), and having at least one long-standing disease (OR 2.6, CI 2.0–3.4). Significant predictors for pain recovery were male gender, younger age, cohabitation status, good self-rated health, good mental health, having no long-standing disease, and having an annual income above US$ 15400.



Pain, Article in Press

Chronic pain patients are impaired on an emotional decision-making task

A. Vania Apkarian, Yamaya Sosa, Beth R. Krauss, P. Sebastian Thomas, Bruce E. Fredrickson, Robert E. Levy, R. Norman Harden and Dante R. Chialvo

            Chronic pain can result in anxiety, depression and reduced quality of life. However, its effects on cognitive abilities have remained unclear although many studies attempted to psychologically profile chronic pain. We hypothesized that performance on an emotional decision-making task may be impaired in chronic pain since human brain imaging studies show that brain regions critical for this ability are also involved in chronic pain. Chronic back pain (CBP) patients, chronic complex regional pain syndrome (CRPS) patients, and normal volunteers (matched for age, sex, and education) were studied on the Iowa Gambling Task, a card game developed to study emotional decision-making. Outcomes on the gambling task were contrasted to performance on other cognitive tasks. The net number of choices made from advantageous decks after subtracting choices made from disadvantageous decks on average was 22.6 in normal subjects (n=26), 13.4 in CBP patients (n=26), and -9.5 in CRPS patients (n=12), indicating poor performance in the patient groups as compared to the normal controls (P<0.004). Only pain intensity assessed during the gambling task was correlated with task outcome and only in CBP patients (r=-0.75, P<0.003). Other cognitive abilities, such as attention, short-term memory, and general intelligence tested normal in the chronic pain patients. Our evidence indicates that chronic pain is associated with a specific cognitive deficit, which may impact everyday behavior especially in risky, emotionally laden, situations.



Pain, Article in Press

Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study

Ron C. Kupers, Peter Svensson and Troels S. Jensen

            Functional neuroimaging studies of the human brain have revealed a network of brain regions involved in the processing of nociceptive information. However, little is known of the cerebral processing of pain originating from muscles. The aim of this study was to investigate the cerebral activation pattern evoked by experimental jaw-muscle pain and its interference by simultaneous mechanical stimuli, which has been shown to evoke hyperesthesia. Ten healthy subjects participated in a PET study and jaw-muscle pain was induced by bolus injections of 5% hypertonic saline into the right masseter muscle. Repeated von Frey hair stimulation (0.5 Hz) of the skin above the masseter muscle was used as the mechanical stimulus. Hypertonic saline injections caused strong muscle pain spreading to adjacent areas. von Frey stimulation was rated as non-painful but produced hyperesthesia during jaw-muscle pain. Jaw-muscle pain was associated with significant increases in regional cerebral blood flow (rCBF) in the dorsal-posterior insula (bilaterally), anterior cingulate and prefrontal cortices, right posterior parietal cortex, brainstem, cavernous sinus and cerebellum. No rCBF changes occurred in primary or secondary somatosensory cortices. In contrast, von Frey stimulation produced a significant rCBF increase in the contralateral SI face representation. Mechanical hyperesthesia was associated with significant rCBF increases in the subgenual cingulate and the ventroposteromedial and dorsomedial thalamus. These results suggest that the cerebral processing of jaw-muscle pain may differ from the processing of cutaneous pain and that mechanical hyperesthesia, which often is encountered in clinical cases, has a unique representation in the brain.



Salomons, Timothy V. ; Osterman, Janet E.; Gagliese, Lucia; Katz, Joel

Pain Flashbacks in Posttraumatic Stress Disorder.

Clinical Journal of Pain. 20(2):83-87, March/April 2004.

            Objectives: Surgical patients who regain consciousness while under general anesthesia may develop symptoms of Posttraumatic Stress Disorder (PTSD). One common PTSD symptom is the experiencing of abnormal perceptions during which the patient feels as if the trauma is recurring. The objective of this report is to document the re-occurrence of pain as part of the PTSD sequelae. Results: We present two patients who developed PTSD following an episode of awareness under anesthesia. In both cases, posttraumatic sequelae persisted for years and included pain symptoms that resembled, in quality and location, pain experienced during surgery. In addition to their similarity to the original pain, these pain symptoms were triggered by stimuli associated with the traumatic situation, suggesting that they were flashbacks to the episode of awareness under anesthesia. Discussion: The similarity between the patients' pain symptoms and pain experienced during trauma, the triggering by traumatic cues, and the associated emotional arousal and avoidance suggest the involvement of a somatosensory memory mechanism.




Pain, Article in Press

Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications

Judith A. Turner, John D. Loeser, Richard A. Deyo and Stacy B. Sanders

            We conducted a systematic review of the literature on the effectiveness of spinal cord stimulation (SCS) in relieving pain and improving functioning for patients with failed back surgery syndrome and complex regional pain syndrome (CRPS). We also reviewed SCS complications. Literature searches yielded 583 articles, of which seven met the inclusion criteria for the review of SCS effectiveness, and 15 others met the criteria only for the review of SCS complications. Two authors independently extracted data from each article, and then resolved discrepancies by discussion. We identified only one randomized trial, which found that physical therapy (PT) plus SCS, compared with PT alone, had a statistically significant but clinically modest effect at 6 and 12 months in relieving pain among patients with CRPS. Similarly, six other studies of much lower methodological quality suggest mild to moderate improvement in pain with SCS. Pain relief with SCS appears to decrease over time. The one randomized trial suggested no benefits of SCS in improving patient functioning. Although life-threatening complications with SCS are rare, other adverse events are frequent. On average, 34% of patients who received a stimulator had an adverse occurrence. We conclude with suggestions for methodologically stronger studies to provide more definitive data regarding the effectiveness of SCS in relieving pain and improving functioning, short- and long-term, among patients with chronic pain syndromes.




Hypervigilance to Pain in Fibromyalgia: The Mediating Role of Pain Intensity and Catastrophic Thinking About Pain

Crombez, Geert PhD, Eccleston, Chris, Van den Broeck, Annelies, Goubert, Liesbet, Van Houdenhove, Boudewijn

Clinical Journal of Pain. 20(2):98-102, March/April 2004

            Objective: To investigate the mediating role of pain intensity, catastrophic thinking about pain, and negative affectivity in explaining enhanced attention for pain in patients with fibromyalgia. Methods: Sixty-four patients with fibromyalgia and 46 patients with chronic low back pain completed self-report instruments of vigilance to pain, negative affectivity, and catastrophic thinking about pain. These measures, along with diagnostic group and pain intensity, were entered into a partial correlational analysis to investigate which variables mediate the relationship between diagnostic group (fibromyalgia vs. chronic low back pain) and vigilance to pain. Results: Fibromyalgia patients reported significantly greater vigilance to pain than patients with chronic low back pain. They also reported higher pain intensity, more negative affectivity, and more catastrophic thinking about pain than patients with chronic low back pain. Vigilance to pain was correlated significantly with pain intensity, negative affectivity, and catastrophic thinking about pain. Further analyses revealed that pain intensity and catastrophic thinking about pain, but not negative affectivity, mediated the relationship between diagnostic group and vigilance to pain. Conclusion: Fibromyalgia patients report a heightened vigilance to pain. This vigilance is not a unique characteristic of fibromyalgia but is related to the intensity of pain and catastrophic thinking about pain.




Confirmatory Factor Analysis of the Tampa Scale for Kinesiophobia: Invariant Two-Factor Model Across Low Back Pain Patients and Fibromyalgia Patients.

Goubert, Liesbet; Crombez, Geert; Van Damme, Stefaan; Vlaeyen, Johan W. S.; Bijttebier, Patricia; Roelofs, Jeffrey

Clinical Journal of Pain. 20(2):103-110, March/April 2004.

            Objectives: (1) To investigate the factor structure of the Tampa Scale for Kinesiophobia (TSK) in a Dutch-speaking sample of chronic low back pain (CLBP) patients using confirmatory factor analysis, (2) to examine whether the internal structure of the TSK extends to another group of fibromyalgia (FM) patients, and (3) to investigate the stability of the factor structure in both patient groups using multi-sample analysis. Patients and Methods: TSK-data from 8 studies collected in Dutch and Flemish chronic pain patients were pooled. For 188 CLBP patients and 89 FM patients, complete data were available. Confirmatory factor analyses were performed to assess 4 models of kinesiophobia, and to examine which factor model provided the best fit. Furthermore, a multi-sample analysis was performed to investigate the stability of the factor structure in both patient groups. Results: For both CLBP and FM patients, the 2-factor model containing the factors "activity avoidance" and "pathologic somatic focus" was superior as compared with the 4-factor model containing the factors "harm," "fear of (re)injury." "importance of exercise," and "avoidance of activity". Moreover, the 2-factor model was found to be invariant across CLBP and FM patients, indicating that this model is robust in both pain samples. Discussion: As the 2-factor structure provided the best fit of the data in both patient samples, we recommend to use this version of the TSK and its 2 subscales in both clinical practice and research. Based on the content of the items, the subscales were labeled "Harm" and "Fear-avoidance."




Smith, Michael T.; Perlis, Michael L.; Haythornthwaite, Jennifer A.

Suicidal Ideation in Outpatients With Chronic Musculoskeletal Pain: An Exploratory Study of the Role of Sleep Onset Insomnia and Pain Intensity.

Clinical Journal of Pain. 20(2):111-118, March/April 2004.

            Objectives: Sleep disturbance, depression, and heightened risk of suicide are among the most clinically significant sequelae of chronic pain. While sleep disturbance is associated with suicidality in patients with major depression and is a significant independent predictor of completed suicide in psychiatric patients, it is not known whether sleep disturbance is associated with suicidal behavior in chronic pain. This exploratory study evaluates the importance of insomnia in discriminating suicidal ideation in chronic pain relative to depression severity and other pain-related factors. Methods: Fifty-one outpatients with non-cancer chronic pain were recruited. Subjects completed a pain and sleep survey, the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, and the Multidimensional Pain Inventory. Subjects were classified as "suicidal ideators" or "non-ideators" based on their responses to BDI-Item 9 (Suicide). Bivariate analyses and multivariate discriminant function analyses were conducted. Results: Twenty-four percent reported suicidal ideation (without intent). Suicidal ideators endorsed higher levels of: sleep onset insomnia, pain intensity, medication usage, pain-related interference, affective distress, and depressive symptoms (P < 0.03). These 6 variables were entered into stepwise discriminant function analyses. Two variables predicted group membership: Sleep Onset Insomnia Severity and Pain Intensity, respectively. The discriminant function correctly classified 84.3% of the cases (P < 0.0001). Discussion: Chronic pain patients who self-reported severe and frequent initial insomnia with concomitant daytime dysfunction and high pain intensity were more likely to report passive suicidal ideation, independent from the effects of depression severity. Future research aimed at determining whether sleep disturbance is a modifiable risk factor for suicidal ideation in chronic pain is warranted.





Headache: The Journal of Head and Face Pain

Volume 43 Issue 10 Page 1042  - November 2003

Exploring the Relationship Between Maternal Migraine and Child Functioning

Maria A. Fagan, MSc

            Objective.To investigate the relationship between mothers' migraines and the roles and expectations of their children. Methods.Twenty-five mothers diagnosed with migraine completed questionnaires concerning their levels of migraine-related disability and their parenting and child-rearing attitudes. Migraine-related disability was assessed using the Migraine-Specific Quality of Life Questionnaire (version 2.1). Parenting and child-rearing attitudes were assessed using the Adult-Adolescent Parenting Inventory. Results.Significant positive relationships were found between the mothers' migraine-related disability and both inappropriate expectations of their children and parent-child role reversal; ie, the more migraine-related disability reported by the mothers, the more they reported having inappropriate expectations of their children and favoring parent-child role reversal. Conclusions.This study suggests that migraine may be associated with dysfunctional parenting patterns. More specifically, it suggests that in families wherein the mother has migraine, children may be at risk of inappropriately or prematurely assuming roles for which they are developmentally unready. Clinical implications are that mothers with migraine may benefit from some type of family-focused intervention, in addition to headache treatment.




Headache: The Journal of Head and Face Pain

Volume 43 Issue 10 Page 1097  - November 2003

Work Attendance Despite Headache and Its Economic Impact: A Comparison Between Two Workplaces

Ragnhild Raak, RN, PhD; Anders Raak, MD

            Objective.To study work attendance despite headache in 2 different workplaces and its economic impact. Background.Literature on the economic impact of headache traditionally has focused on direct costs. Little is known concerning headache experienced at work and its costs due to loss of effectiveness and productivity. Method.We sent a questionnaire to 800 employees in Sweden400 at a technology company (private employee population) and 400 at a university hospital (public employee population). We attempted to assess the prevalence of headache, work attendance despite the presence of acute headache, and the impact of acute headache upon work effectiveness. Subjects self-scored decreased work effectiveness resulting from headache during the previous 3 months and recorded the number of days at work despite headache. From these data, we estimated the economic loss resulting from headache. Results.The survey response rate was 71.5%. The prevalence of headache was 64% in the private employee population and 78% in the public employee population. Thirty-nine percent of the private employees and 57% of the public employees reported experiencing headache as a result of stress. Fifty percent reported that they went to work despite headache, and the mean number of days at work despite headache, during the previous 3 months, was 6.6 days in the private employee group and 6.1 days in the public employee group. A 25% decrease in work effectiveness was estimated, and, extrapolating from our data, we calculated the cost of lost effectiveness due to headache among employers in Sweden to be approximately 1.4 billion euros a year. Conclusion.The economic burden of headache experienced at work is substantial, suggesting that workplace-based treatment and prevention programs emphasizing stress management may be financially, as well as clinically, advantageous.




Headache: The Journal of Head and Face Pain

Volume 43 Issue 10 Page 1049  - November 2003

Migraine Frequency and Intensity: Relationship With Disability and Psychological Factors

Jane E. Magnusson, PhD; Werner J. Becker, MD

            Background.Migraine can be disabling, but it varies greatly in frequency and intensity between individuals. It is not clear which clinical features have the greatest impact on a migraineur's quality of life. Objective.To determine the influence of headache intensity and frequency on headache-related disability. Methods.Patients who were referred to a headache clinic and given a diagnosis of migraine with or without aura or transformed migraine (n = 115) were divided into different groups based on headache frequency and mean headache intensity. Headache frequency was determined from patient diaries. Headache intensity also was assessed from patient diaries and from scores on the pain severity scale of the Multidimensional Pain Inventory (MPI). Headache-related disability was assessed with the Headache Disability Inventory and by scores on the activity interference scale of the MPI. The degree of depression present was assessed with the Beck Depression Inventory, and emotional distress was measured by scores on the affective distress scale of the MPI. Results.In our patient population, higher mean headache intensity levels were associated with higher levels of headache-related disability. Our results also suggested that increased headache intensity is associated with higher levels of depression and emotional distress, although this correlation was statistically significant in only 1 of 4 comparisons. Headache frequency did not correlate with disability, depression, or emotional distress. Conclusions.For a headache referral population, headache intensity appears to be a major determinant of headache-related disability, and it also correlates, to some extent, with the degree of depression and emotional distress present. Headache frequency was not clearly related to disability or psychological factors.