FIBRO*

Endocrine. 2003 Oct;22(1):67-76.

Fibromyalgia: symptom constellation and potential therapeutic options.

Shuer ML. Mood & Menopause Clinic, P.O. Box 462223, Escondido, CA 92046-2223, USA. MLShuer@ispwest.com

Fibromyalgia (FM) is a disease entity consisting of a heterogeneous cluster of symptoms that has thus far eluded identification of a causative etiology. The disease onset appears to follow physiological and/or psychological stressors and involves a subset of symptoms that are consistent with varied disorders found in multiple medical specialties to include rheumatology, immunology, endocrinology, neurology, and psychiatry. Owing to the heterogeneity of the symptom complex and the heretofore absence of serum markers that might serve as concrete diagnostic criteria, this disease has baffled clinicians and basic scientists alike. Recent findings regarding sleep architecture, immunology, and endocrinology have provided clues that may help in the understanding and resultant treatment of this entity.

Women with fibromyalgia tend to present with an alpha-delta sleep anomaly, which when treated with a growth hormone secretagogue (GHS), reduces the rheumatological pain and restores slow-wave sleep architecture. These findings suggest the somatotrophic axis may be involved in the etiology and the treatment of this disorder. Those diagnosed with FM respond to various stressors with increased disruption of their physiological homeostasis. When compared to healthy age-matched cohorts, there are quantitative differences in various neuroactive steroid levels, immunological markers, and feedback mechanisms. The varied physiological alterations in patients diagnosed with fibromyalgia when compared to controls will be discussed along with the potential treatment options for this population.

Anesth Analg. 2003 Dec;97(6):1730-9.

Ketamine in chronic pain management: an evidence-based review.

Hocking G, Cousins MJ. Pain Management and Research Centre, University of Sydney, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.

Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.

Curr Pain Headache Rep. 2003 Dec;7(6):433-42.

Evaluation of treatments for myofascial pain syndrome and fibromyalgia.

Rudin NJ. nj.rudin@hosp.wisc.edu

Myofascial pain syndrome (MPS) and fibromyalgia (FM) are complex conditions and pose significant challenges to clinicians and patients. This chapter explores available treatments for MPS and FM in the context of pathophysiology, clinical evidence, and experimental support. This information may prove to be helpful in designing individualized treatment for patients with these complex syndromes. New treatments should be critically and carefully evaluated as they appear.

Curr Pain Headache Rep. 2003 Dec;7(6):426-32.

Hypersensitivity in muscle pain syndromes.

Henriksson KG. karl-g@telia.com

The aim of this review is to present research that has a bearing on the pathogenesis of hypersensitivity in muscle pain syndromes. Allodynia and hyperalgesia in these syndromes can be segmental or generalized and temporary or permanent. Hypersensitivity in muscle pain conditions in the clinic is best diagnosed by determining the pressure pain threshold. In a disorder such as fibromyalgia, decreased pain thresholds also are found at sites where there is no tenderness. Pathogenetic mechanisms for allodynia and hyperalgesia can be identified at several levels of the nociceptive system, from the nociceptors in the muscle to the cortex. Central sensitization of nociceptive neurons in the dorsal horn and a disturbed balance between inhibitory and facilitatory impulses in the descending tracts from the brain stem to the dorsal horn are the main mechanisms for pain hypersensitivity. Changes in function, biochemical make-up, and synaptic connections in the nociceptive neurons in the dorsal horn are considered to be caused by neuronal plasticity.

Orthop Nurs. 2003 Sep-Oct;22(5):353-60. Related Articles, Links

Effects of T'ai Chi exercise on fibromyalgia symptoms and health-related quality of life.

Taggart HM, Arslanian CL, Bae S, Singh K. Armstrong Atlantic State University, Savannah, GA, USA.

BACKGROUND: Fibromyalgia (FM), one of the most common musculoskeletal disorders, is associated with high levels of impaired health and inadequate or limited symptom relief. The cause of this complex syndrome is unknown, and there is no known cure. Numerous research results indicate that a combination of physical exercise and mind-body therapy is effective in symptom management. T'ai Chi, an ancient Chinese exercise, combines physical exercise with mindbody therapy. PURPOSE: To investigate the effects of T'ai Chi exercise on FM symptoms and health-related quality of life. DESIGN: Pilot study, one group pre-to-post posttest design. METHODS: Participants with FM (n = 39) formed a single group for 6 weeks of 1-hour, twice weekly T'ai Chi exercise classes. FM symptoms and health-related quality of life were measured before and after exercise. FINDINGS: Twenty-one participants completed at least 10 of the 12 exercise sessions. Although the dropout rate was higher than expected, measurements on both the Fibromyalgia Impact Questionnaire (FIQ) (Buckhardt, Clark, & Bennett, 1991) and the Short Form-36 (SE-36) (Ware & Sherbourne, 1992) revealed statistically significant improvement in symptom management and health-related quality of life. IMPLICATIONS FOR NURSING RESEARCH: Knowledge of interventions to enhance health for the patient with musculoskeletal problems is a National Association of Orthopaedic Nurses priority. Tai Chi is potentially beneficial to patients with FM. Further research is needed to support evidence-based practice.

Ann Pharmacother. 2003 Nov;37(11):1561-5.

Venlafaxine treatment of fibromyalgia.

Sayar K, Aksu G, Ak I, Tosun M. mkemalsayar@superonline.com

BACKGROUND: Although the pathophysiology of fibromyalgia is unknown, central monoaminergic transmission may play a role. Antidepressants have proved to be successful in alleviating symptoms of fibromyalgia. Medications that act on multiple neurotransmitters may be more effective in symptom management. OBJECTIVE: To assess the efficacy of venlafaxine, a potent inhibitor of both norepinephrine and serotonin reuptake, in the treatment of patients with fibromyalgia. METHODS: Fifteen patients with fibromyalgia were assessed prior to and after treatment with fixed-dose venlafaxine 75 mg/d. Before initiation of pharmacotherapy, patients were interviewed with the Structured Clinical Interview for Axis I disorders in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The study lasted for 12 weeks, and patients were evaluated in weeks 6 and 12. The primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) total score and pain score. The anxiety and depression levels of the patients were measured with the Beck Depression, the Beck Anxiety, the Hamilton Anxiety, and the Hamilton Depression scales. RESULTS: There was a significant improvement in the mean intensity of pain (F = 14.3; p = 0.0001) and in the disability caused by fibromyalgia (F = 42.7; p = 0.0001) from baseline to week 12 of treatment. The depression and anxiety scores also decreased significantly from baseline to week 12. The improvement in the FIQ scores did not correlate with the decrease of scores in both patient- and physician-rated depression and anxiety inventories. Change in pain scores also was not correlated with the change in depression and anxiety scores. CONCLUSIONS: Venlafaxine was quite promising in alleviating the pain and disability associated with fibromyalgia. This effect seems to be independent of its anxiolytic and antidepressant properties. Blockade of both norepinephrine and serotonin reuptake might be more effective than blockade of either neurotransmitter alone in the treatment of fibromyalgia.

J Med Virol. 2003 Dec;71(4):540-7.

Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects.

Douche-Aourik F, Berlier W, Feasson L, Bourlet T, Harrath R, Omar S, Grattard F, Denis C, Pozzetto B.

Enterovirus RNA has been found previously in specimens of muscle biopsy from patients with idiopathic dilated cardiomyopathy, chronic inflammatory muscle diseases, and fibromyalgia or chronic fatigue syndrome (fibromyalgia/chronic fatigue syndrome). These results suggest that skeletal muscle may host enteroviral persistent infection. To test this hypothesis, we investigated by reverse transcription-polymerase chain reaction (RT-PCR) assay the presence of enterovirus in skeletal muscle of patients with chronic inflammatory muscle diseases or fibromyalgia/chronic fatigue syndrome, and also of healthy subjects. Three of 15 (20%) patients with chronic inflammatory muscle diseases, 4 of 30 (13%) patients with fibromyalgia/chronic fatigue syndrome, and none of 29 healthy subjects was found positive. The presence of VP-1 enteroviral capsid protein was assessed by an immunostaining technique using the 5-D8/1 monoclonal antibody; no biopsy muscle from any patient or healthy subject was found positive. The presence of viral RNA in some muscle biopsies from patients exhibiting muscle disease, together with the absence of VP-1 protein, is in favor of a persistent infection involving defective viral replication.

J ECT. 2003 Dec;19(4):226-9.

Electroconvulsive therapy in complex regional pain syndromes.

McDaniel WW. Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA. mcdaniww@evms.edu

Three cases are presented in which electroconvulsive therapy (ECT) for depression led to the relief of comorbid complex regional pain syndrome as well as depression. In one of the cases, concomitant fibromyalgia was not relieved during 2 separate series of ECT. The literature regarding the role of ECT in the management of chronic pain is reviewed and discussed in light of recent findings about ECT and changes in neurotransmission associated with seizures.

Best Pract Res Clin Rheumatol. 2003 Aug;17(4):667-83.

Complementary and alternative medicine in fibromyalgia and related syndromes.

Holdcraft LC, Assefi N, Buchwald D. holdcraf@u.washington.edu

Complementary and alternative medicine (CAM) has gained increasing popularity, particularly among individuals with fibromyalgia syndrome (FMS) for which traditional medicine has generally been ineffective. A systematic review of randomized controlled trials (RCTs) and non-RCTs on CAM studies for FMS was conducted to evaluate the empirical evidence for their effectiveness. Few RCTs achieved high scores on the CONSORT, a standardized evaluation of the quality of methodology reporting. Acupuncture, some herbal and nutritional supplements (magnesium, SAMe) and massage therapy have the best evidence for effectiveness with FMS. Other CAM therapies have either been evaluated in only one RCT with positive results (Chlorella, biofeedback, relaxation), in multiple RCTs with mixed results (magnet therapies), or have positive results from studies with methodological flaws (homeopathy, botanical oils, balneotherapy, anthocyanidins, dietary modifications). Lastly, other CAM therapies have neither well-designed studies nor positive results and are not currently recommended for FMS treatment (chiropractic care).

J Rheumatol. 2003 Oct;30(10):2257-62.

The efficacy of mindfulness meditation plus Qigong movement therapy in the treatment of fibromyalgia: a randomized controlled trial.

Astin JA, Berman BM, Bausell B, Lee WL, Hochberg M, Forys KL. jastin@cooper.cpmc.org

OBJECTIVE: To test the short and longterm benefits of an 8 week mind-body intervention that combined training in mindfulness meditation with Qigong movement therapy for individuals with fibromyalgia syndrome (FM). METHODS: A total of 128 individuals with FM were randomly assigned to the mind-body training program or an education support group that served as the control. Outcome measures were pain, disability (Fibromyalgia Impact Questionnaire), depression, myalgic score (number and severity of tender points), 6 minute walk time, and coping strategies, which were assessed at baseline and at 8, 16, and 24 weeks. RESULTS: Both groups registered statistically significant improvements across time for the Fibromyalgia Impact Questionnaire, Total Myalgic Score, Pain, and Depression, and no improvement in the number of feet traversed in the 6 minute walk. However, there was no difference in either the rate or magnitude of these changes between the mind-body training group and the education control group. Salutary changes occurring by the eighth week (which corresponded to the end of the mind-body and education control group sessions) were largely maintained by both groups throughout the 6 month followup period. CONCLUSION: While both groups showed improvement on a number of outcome variables, there was no evidence that the multimodal mind-body intervention for FM was superior to education and support as a treatment option. Additional randomized controlled trials are needed before interventions of this kind can be recommended for treatment of FM.

Arthritis Rheum. 2003 Oct;48(10):2916-22.

Subgrouping of fibromyalgia patients on the basis of pressure-pain thresholds and psychological factors.

Giesecke T, Williams DA, Harris RE, Cupps TR, Tian X, Tian TX, Gracely RH, Clauw DJ. University of Michigan, Ann Arbor, USA.

OBJECTIVE: Although the American College of Rheumatology (ACR) criteria for fibromyalgia are used to identify individuals with both widespread pain and tenderness, individuals who meet these criteria are not a homogeneous group. Patients differ in their accompanying clinical symptoms, as well as in the relative contributions of biologic, psychological, and cognitive factors to their symptom expression. Therefore, it seems useful to identify subsets of fibromyalgia patients on the basis of which of these factors are present. Previous attempts at identifying subsets have been based solely on psychological and cognitive features. In this study, we attempt to identify patient subsets by incorporating these features as well as the degree of hyperalgesia/tenderness, which is a key neurobiologic feature of this illness. METHODS: Ninety-seven individuals meeting the ACR criteria for fibromyalgia finished the same battery of self-report and evoked-pain testing. Analyzed variables were obtained from several domains, consisting of 1) mood (evaluated by the Center for Epidemiologic Studies Depression Scale [for depression] and the State-Trait Personality Inventory [for symptoms of trait-related anxiety]), 2) cognition (by the catastrophizing and control of pain subscales of the Coping Strategies Questionnaire), and 3) hyperalgesia/tenderness (by dolorimetry and random pressure-pain applied at suprathreshold values). Cluster analytic procedures were used to distinguish subgroups of fibromyalgia patients based on these domains. RESULTS: Three clusters best fit the data. Multivariate analysis of variance (ANOVA) confirmed that each variable was differentiated by the cluster solution (Wilks' lambda [degrees of freedom 6,89] = 0.123, P < 0.0001), with univariate ANOVAs also indicating significant differences (all P < 0.05). One subgroup of patients (n = 50) was characterized by moderate mood ratings, moderate levels of catastrophizing and perceived control over pain, and low levels of tenderness. A second subgroup (n = 31) displayed significantly elevated values on the mood assessments, the highest values on the catastrophizing subscale, the lowest values for perceived control over pain, and high levels of tenderness. The third group (n = 16) had normal mood ratings, very low levels of catastrophizing, and the highest level of perceived control over pain, but these subjects showed extreme tenderness on evoked-pain testing. CONCLUSION: These data help support the clinical impression that there are distinct subgroups of patients with fibromyalgia. There appears to be a group of fibromyalgia patients who exhibit extreme tenderness but lack any associated psychological/cognitive factors, an intermediate group who display moderate tenderness and have normal mood, and a group in whom mood and cognitive factors may be significantly influencing the symptom report.

Pain. 2003 Oct;105(3):385-6.

Hyperalgesia versus response bias in fibromyalgia.

Fillingim RB. These results extend a large body of work demonstrating that FM is characterized by generalized hyperalgesia. The vestiges of Cartesian dualism remain evident as scientists and clinicians debate whether these findings should be attributed to neurobiological mechanisms or psychological influences. Petzke et al. (2003) provide a helpful redefinition of this issue by addressing whether enhanced pain responses in FM patients are explained by psychological influences on ‘ reporting’ Their sophisticated psychophysics revealed that psychological factors, such as expectancy or hypervigilance, do not explain the greater pain responding by FM patients. Does this imply that psychological factors are unimportant in the hyperalgesia of FM patients? In answering this question, it is important to recognize that in addition to their impact on pain reporting, psychological factors also alter pain responses through direct effects on nociceptive processing. For example, abundant literature on placebo responses indicates that expectations of imminent pain relief produce an endogenous opioid-mediated reduction in pain (Benedetti and Amanzio, 1997). Also, distraction reduces pain reporting in humans, and several studies in behaving monkeys have demonstrated that attentional redirection decreased activity in both spinal and thalamic nociceptive neurons (Villemure and Bushnell, 2002). This distinction between psychological influences on responding versus pain processing often goes unnoticed. Petzke et al. (2003) demonstrated no group differences in the impact of psychological factors specifically on pain reporting; however, group differences in nociceptive processing were observed and psychological factors may well have contributed to these differences. Indeed, the authors point this out in the last paragraph of the paper. Thus, an important implication of these findings is that any contribution of psychological factors to altered pain sensitivity in FM patients may be due to direct effects on nociceptive processing rather than to influences on pain reporting behavior.

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.

**Pain. 2003 Oct;105(3):403-13.

Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation.

Petzke F, Clauw DJ, Ambrose K, Khine A, Gracely RH.

Fibromyalgia (FM) is defined in part by sensitivity to blunt pressure. Pressure pain sensitivity in FM is evaluated typically by the use of 'ascending' testing methods such as tender point counts or dolorimetry, which can be influenced by response bias of both the subject and examiner. Methods that present stimuli in a random, unpredictable fashion might minimize the influence of these factors. In this study, we compared the results of ascending and random assessments of both pressure and thermal pain sensitivities in 43 FM patients and 28 age- and gender-matched controls. Even though FM is defined on the basis of pressure sensitivity, this group was also more sensitive to heat stimuli, presented in either ascending or random paradigms. In both the patient and control groups, the pain ratings to painful sensations evoked by both thermal and pressure stimuli were significantly greater in the random, compared with the ascending method. The number of subjects classified as 'expectant' because they rated pain higher in ascending than random paradigms was similar for FM and control groups. Both patients and controls exhibited a similar degree of sensitization to pressure and thermal stimuli. The increased sensitivity to both pressure and thermal stimuli for threshold and suprathreshold stimuli in FM patients is consistent with central augmentation of pain processing.

Expert Opin Pharmacother. 2003 Oct;4(10):1687-95.

Current trends in fibromyalgia research.

Marcus DA. Pain Evaluation & Treatment Institute, 5750 Centre Avenue, Pittsburgh, PA 15206, USA. dawnpainmd@yahoo.com

The development of standardised criteria for the diagnosis of fibromyalgia in 1990 has allowed careful study of this chronically painful syndrome. Epidemiological studies show increased symptoms and disability in patients with fibromyalgia, compared with other conditions associated with chronic, widespread pain. In addition, prevalence and severity of fibromyalgia symptoms are increased in women. Current studies have identified strong evidence for central sensitisation in fibromyalgia. Data from these studies may expand effective treatment options for fibromyalgia.

J Hand Surg [Am]. 2003 Nov;28(6):894-7.

Diagnosis of compressive neuropathies in patients with fibromyalgia.

Dellon AL, Shookster LA, Maloney CT Jr, Ducic I. Division of Plastic Surgery and Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, USA

The hand surgeon relies on the Tinel sign in the physical examination of the patient suspected of having a peripheral nerve entrapment. Fibromyalgia is recognized by the American College of Rheumatology as a condition characterized by having tender points on physical examination. This article reviews the location of the 9 bilateral critical diagnostic fibromyalgia points as they relate to known sites of anatomic entrapment of peripheral nerves in the upper extremity. The interpretation of this article is that the Tinel sign may be used with validity to identify the site of a peripheral nerve compression in the upper extremity in the patient with fibromyalgia.

Yonsei Med J. 2003 Aug 30;44(4):619-22. Related Articles, Links

The role of tendinitis in fibromyalgia syndrome.

Genc H, Saracoglu M, Duyur B, Erdem HR. hakangenc06@hotmail.com

Fibromyalgia Syndrome (FS) is a common disease characterized by diffuse, widespread pain and multiple tender points. The syndrome has been subclassified as primary (PFS) and secondary (SFS) fibromyalgia. The aim of this study was to evaluate the role of common tendinitis (rotator cuff tendinitis, bicipital tendinitis, lateral epicondylitis, De-Quervain's tendinitis and pes anserinus tendinitis) in FS. Twenty female patients with PFS, 20 with SFS and 20 female controls, matched by age and body mass index, participated in the study. Existence of common tendinitis was evaluated with specific examination methods. Right and left rotator cuff tendinitis, pes anserinus tendinitis and left lateral epicondylitis were significantly more common in patients with PFS and SFS than in control subjects. As a result, considering the central hyperexcitability present in the fibromyalgia patients, concomitant pathologies such as tendinitis which lead to shoulder, arm, and leg pain must be evaluated. Follow up and therapy for the disease must be planned according to these factors which are not only probable symptoms of FS, but also leading causes for the occurrence and continuity of the pain in this disease.

Brain. 2004 Apr;127(Pt 4):835-43. Epub 2004 Feb 11.

Pain catastrophizing and neural responses to pain among persons with fibromyalgia.

Gracely RH, Geisser ME, Giesecke T, Grant MA, Petzke F, Williams DA, Clauw DJ. dclauw@med.umich.edu

Pain catastrophizing, or characterizations of pain as awful, horrible and unbearable, is increasingly being recognized as an important factor in the experience of pain. The purpose of this investigation was to examine the association between catastrophizing, as measured by the Coping Strategies Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure assessed by functional MRI among 29 subjects with fibromyalgia. Since catastrophizing has been suggested to augment pain perception through enhanced attention to painful stimuli, and heightened emotional responses to pain, we hypothesized that catastrophizing would be positively associated with activation in structures believed to be involved in these aspects of pain processing. As catastrophizing is also strongly associated with depression, the influence of depressive symptomatology was statistically removed. Residual scores of catastrophizing controlling for depressive symptomatology were significantly associated with increased activity in the ipsilateral claustrum (r = 0.51, P < 0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47, P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P < 0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified as high or low catastrophizers, based on a median split of residual catastrophizing scores, showed that both groups displayed significant increases in ipsilateral secondary somatosensory cortex (SII), although the magnitude of activation was twice as large among high catastrophizers. Both groups also had significant activations in contralateral insula, SII, primary somatosensory cortex (SI), inferior parietal lobule and thalamus. High catastrophizers displayed unique activation in the contralateral anterior ACC, and the contralateral and ipsilateral lentiform. Both groups also displayed significant ipsilateral activation in SI, anterior and posterior cerebellum, posterior cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest that pain catastrophizing, independent of the influence of depression, is significantly associated with increased activity in brain areas related to anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain (claustrum, closely connected to amygdala) and motor control. These results support the hypothesis that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. Activation associated with catastrophizing in motor areas of the brain may reflect expressive responses to pain that are associated with greater pain catastrophizing.

Adv Nurse Pract. 2003 Nov;11(11):34-8, 41-3.

Evidence-based management of the fibromyalgia patient. In search of optimal functioning.

Wassem RA, Stillion-Allen KA. University of Utah College of Nursing, Salt Lake City, USA.

Theor Med Bioeth. 2003;24(4):345-54.

Signification and pain: a semiotic reading of fibromyalgia.

Quintner J, Buchanan D, Cohen M, Taylor A. quintner@aceonline.com.au

Patients with persistent pain who lack a detectable underlying disease challenge the theories supporting much of biomedical body-mind discourse. In this context, diagnostic labeling is as inherently vulnerable to the same pitfalls of uncertainty that beset any other interpretative endeavour. The end point is often no more than a name rather than the discovered essence of a pre-existent medical condition. In 1990 a Committee of the American College of Rheumatology (ACR) formulated the construct of Fibromyalgia in an attempt to rectify a situation of diagnostic confusion faced by patients presenting with widespread pain. It was proposed that Fibromyalgia existed as a "specific entity", separable from but curiously able to co-exist with any other painful condition. Epistemological and semiotic analyses of Fibromyalgia have failed to find any sign, clinical or linguistic, which could differentiate it from other diffuse musculoskeletal pain states. The construct of Fibromyalgia sought to define a discernable reality outside the play of language and to pass it off as a natural phenomenon. However, because it has failed both clinically and semiotically, the construct also fails the test of medical utility for the subject in persistent pain.

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. 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.

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.

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.

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.

Schmerz. 2003 Dec;17(6):459-63. [What is different about muscle pain?] [Article in German]

Mense S. mense@urz.uni-heidelberg.de

BACKGROUND: The bulk of available knowledge about pain mechanisms is derived from studies on cutaneous pain. However, deep somatic pain (from muscle, fascia, tendon, joint) is clinically of much greater importance. The existing subjective differences between muscle and skin pain (e.g. muscle pain is poorly localized and shows referral) suggest that muscle and skin pain do not share the same mechanisms. AIMS OF THE STUDY: To answer the question if the nociceptive information from muscle has neuroanatomical connections and mechanisms that are distinct from those of cutaneous nociception. MATERIALS AND METHODS: The results were obtained partly in animal experiments on anaesthetised rats, partly in studies with healthy subjects or fibromyalgia patients. RESULTS: 1. At the spinal level, the excitatory effects of unmyelinated afferent fibres from muscle are subject to a strong segmental inhibition by myelinated afferent fibres, which is largely absent in the effects of cutaneous C fibres. 2. At the cortical level, experimental muscle pain excites other regions than does cutaneous pain. 3. At the level of descending pain-modulating pathways, interruption of the activity in these pathways leads to higher activity of nociceptive neurones caudal to the site of interruption. The activity was higher in neurones with input from deep nociceptors than in cells mediating cutaneous nociception. CONCLUSIONS: The data demonstrate that at all central nervous levels the connections and processing of nociceptive information from muscle and skin are different. The findings regarding descending pain-modulating pathways suggest that a dysfunction of this system could lead to chronic deep pain as in fibromyalgia.

Schmerz. 2003 Dec;17(6):464-74.

[Diagnosis and clinical signs of fibromyalgia] [Article in German]

Conrad I. conrad.ingomar@mh-hannover.de

According to the criteria of the American College of Rheumatology (ACR 1990) fibromyalgia can be classified as a complex of clinical symptoms. It is characterised by widespread muscle pain, and pain in at least 11 out of 18 defined so-called tender points. The widespread muscle pain must be present for at least 3 months. For the diagnosis of fibromyalgia many other rheumatological, neurological and psychiatric diseases have to be excluded; additional autonomic or functional symptoms are usual. Routine laboratory or radiological examinations yield normal results. From a pathogenetic point of view endocrine disturbances and psychosocial stress factors are found. In most cases the clinical course shows a slow development of generalised pain.

Rev Enferm. 2003 Oct;26(10):24-32. [Fibromyalgia, or whole body pain] [Article in Spanish] Ortega Fernandez JA, Poza Vacas BM, Ortiz Jimenez MA, Marin Moreno ME. Psicologia Clinica, USM Alzira, Valencia.

Fibromyalgia is a rheumatic syndrome which is being recognized and diagnosed more often all the time. Its symptoms include a general state of pain not localized in the joints, combined with tremendous tiredness and sleep alterations. Although its exact etiology is still unknown, medical professionals speculate on the existence of multiple cause factors.

Therefore, an integrated therapeutic treatment having the coordinated participation of medical professionals from different fields of expertise is necessary. Mental health professionals play an important role since it is proven the existence of psychological and socio-psychological factors at the start, during the duration of and in the evolution of this syndrome.

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. 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 (disabilitypension 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.

Fibromyalgia, Hepatitis C Infection, and the Cytokine Connection

Mollie E Thompson MD and André Barkhuizen MD Current Pain and Headache Reports 2003 7:342-347

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.

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.

J Affect Disord. 2003 Jun;75(1):77-82.

Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls.

Malt EA, Olafsson S, Aakvaag A, Lund A, Ursin H. eva.albertson@psych.uib.no BACKGROUND: To what extent fibromyalgia belongs to affective spectrum disorders or anxiety spectrum disorders remains disputed. Buspirone induces a hypothermic response, which most likely is due to 5-HT(1A) autoreceptor stimulation, and growth hormone (GH) release, which probably is related to postsynaptic 5-HT(1A) receptor stimulation. The prolactin response to buspirone has been suggested to be mediated through dopamine (DA) antagonistic effects. OBJECTIVES: Based on the assumption that fibromyalgia is more strongly related to stress and anxiety than affective spectrum disorders, we hypothesized that compared to population controls, fibromyalgia patients should demonstrate an increased prolactin response (DA sensitivity) to buspirone challenge test, but no difference in hypothermic response or GH release (5HT sensitivity). METHOD: A 60-mg dose of buspirone was given orally to 22 premenopausal women with fibromyalgia and 14 age and sex matched healthy control subjects. Core body temperature, growth hormone and prolactin levels were analyzed at baseline and after 60, 90, and 150 min. RESULTS: Fibromyalgia patients showed an augmented prolactin response to buspirone compared to controls. Temperature and growth hormone responses did not differ from controls. CONCLUSIONS: Dopaminergic rather than serotonergic neurotransmission is altered in fibromyalgia, suggesting increased sensitivity or density of dopamine D(2) receptors in fibromyalgia patients. Stress and anxiety is an important modulator of dopaminergic neurotransmission. Our results suggest that fibromyalgia is related to anxiety and associated with disturbance in the stress response systems.

Neuroreport. 2003 Mar 24;14(4):619-21.

Retrosplenial cortical activation in the fibromyalgia syndrome.

Wik G, Fischer H, Bragee B, Kristianson M, Fredrikson M. gustav.wik@psyk.uib.no

To study the CNS in chronic muscular pain typical of fibromyalgia we compared PET measures of regional cerebral blood flow (rCBF) in eight fibromyalgic patients and controls at rest. Higher rCBF for patients than controls was found bilaterally in the retrosplenial cortex. Lower rCBF for patients than controls were seen in the left frontal, temporal, parietal, and occipital cortices. The higher retroplenial rCBF in patients than controls may reflect increased attention towards sub-noxious somatosensory signaling, and agrees with the notion that fibromyalgic pain reflects secondary hyperalgesia. The brain regions with lower rCBF in fibromyalgic patients than controls participate in the normal cognitive processing of pain, which may be dysfunctional in fibromyalgia.

***CES Treatment Efficacy STUDIES (Several...)

Eur J Pain. 2004;8(2):163-71.

Peripheral effects of needle stimulation (acupuncture) on skin and muscle blood flow in fibromyalgia.

Sandberg M, Lindberg LG, Gerdle B.

Acupuncture has become a widely used treatment modality in various musculoskeletal pain conditions. Acupuncture is also shown to enhance blood flow and recovery in surgical flaps. The mechanisms behind the effect on blood flow were suggested to rely on vasoactive substances, such as calcitonin gene-related peptide, released from nociceptors by the needle stimulation. In a previous study on healthy subjects, one needle stimulation into the anterior tibial muscle was shown to increase both skin and muscle blood flow. The aim of this study was to examine the effect of needle stimulation on local blood flow in the anterior tibial muscle and overlying skin in patients suffering from a widespread chronic pain condition. Fifteen patients with fibromyalgia (FM) participated in the study. Two modes of needling, deep muscle stimulation and subcutaneous needle insertion were performed at the upper anterior aspect of the

tibia, i.e., in an area without focal pathology or ongoing pain in these patients. Blood flow changes were assessed non-invasively by photoplethysmography (PPG). The results of the present study were partly similar to those earlier found at a corresponding site in healthy female subjects, i.e., deep muscle stimulation resulted in larger increase in skin blood flow (mean (SE)): 62.4% (13.0) and muscle blood flow: 93.1% (18.6), compared to baseline, than did subcutaneous insertion (mean (SE) skin blood flow increase: 26.4% (6.2); muscle blood flow increase: 46.1% (10.2)). However, in FM patients subcutaneous needle insertion was followed by a significant increase in both skin and muscle blood flow, in contrast to findings in healthy subjects where no significant blood flow increase was found following the subcutaneous needling. The different results of subcutaneous needling between the groups (skin blood flow: [Formula: see text]; muscle blood flow: [Formula: see text] ) may be related to a greater sensitivity to pain and other somatosensory input in FM.

J Endocrinol Invest. 2004 Jan;27(1):42-6.

Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.

Calis M, Gokce C, Ates F, Ulker S, Izgi HB, Demir H, Kirnap M, Sofuoglu S, Durak AC, Tutus A, Kelestimur F.

Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

Minerva Med. 2004 Feb;95(1):35-52.

Fibromyalgia: state of the art.

Fietta P. Rheumatic Disease and Internal Medicine Unit, Osteo-Articular Department, Hospital of Parma, Parma, Italy.

Fibromyalgia (FM) is a common and complex condition, defined as long lasting, widespread musculoskeletal pain, in the presence of tender points (TPs) at specific anatomical sites. Dysautonomic and functional symptoms, such as orthostatic hypotension, tachycardia, effort intolerance, marked fatigue, sleep disorders, cognitive disturbances, psychological distress, paresthesias, headache, genitourinary manifestations, irritable bowel syndrome and bladder dyskinesia, frequently occur. The etiopathogenesis of FM is presently unknown, but nociceptor, autonomic and neuro-endocrine system dysfunctions have been found in patients. Since specific serological or instrumental markers of the syndrome are not yet identifiable, TP search is the only useful diagnostic hallmark. The development of an effective therapy of FM has hitherto been hampered by the incomplete knowledge of its pathogenic mechanisms. In this paper, the most recent information on FM is reviewed.

Psychother Psychosom Med Psychol. 2004 Mar;54(3-4):137-47.

[Fibromyalgia as a dysfunction of the central pain and stress response] [Article in German]

Egle UT, Ecker-Egle ML, Nickel R, Van Houdenhove B. egle@psychosomatik.klinik.uni-mainz.de Fibromyalgia is often understood as a syndrome mainly characterised by widespread pain and tenderness and "unexplained" etiology and pathogenesis. In the last years evidence is growing that biological as well as psychosocial stress play a pathogenetic key-role. Beginning with the general function and development of the stress response system the actual knowledge of its relationship with central pain-processing mechanisms is reviewed. Early adverse childhood experiences can impair the function of the stress system all over the lifespan. Subsequently, research evidence for the role of stress in the etiopathogenesis of fibromyalgia is summarised. Psychological as well as psychobiological consequences are outlined. Finally, an integrative model of fibromyalgia is proposed, which may put several pieces of a biopsychosocial puzzle together. This model offers an approach for the differentiation of subgroups and a clinical orientation for developing an adequate therapy for the individual patient.

Arthritis Rheum. 2004 Mar;50(3):944-52.

Family study of fibromyalgia.

Arnold LM, Hudson JI, Hess EV, Ware AE, Fritz DA, Auchenbach MB, Starck LO, Keck PE Jr. Lesley.Arnold@uc.edu

OBJECTIVE: To assess for familial aggregation of fibromyalgia (FM) and measures of tenderness and pain, and for familial coaggregation of FM and major mood disorder (major depressive disorder or bipolar disorder). METHODS: Probands meeting the American College of Rheumatology criteria for FM and control probands with rheumatoid arthritis (RA) and no lifetime diagnosis of FM were recruited from consecutive referrals to 2 community-based rheumatology practices. Probands were ages 40-55 years and had at least 1 first-degree relative age 18 years or older who was available for interview and examination. All probands and interviewed relatives underwent a dolorimeter tender point examination and a structured clinical interview. Interviewed relatives were asked about first-degree relatives who were not available for interview, using a structured family interview. Logistic and linear regression models, adjusting for the correlation of observation within families, were applied to study the aggregation and coaggregation effects. RESULTS: Information was collected for 533 relatives of 78 probands with FM and 272 relatives of 40 probands with RA. FM aggregated strongly in families: the odds ratio (OR) measuring the odds of FM in a relative of a proband with FM versus the odds of FM in a relative of a proband with RA was 8.5 (95% confidence interval [95% CI] 2.8-26, P = 0.0002). The number of tender points was significantly higher, and the total myalgic score was significantly lower in the relatives of probands with FM compared with the relatives of probands with RA. FM coaggregated significantly with major mood disorder: the OR measuring the odds of major mood disorder in a relative of a proband with FM versus the odds of major mood disorder in a relative of a proband with RA was 1.8 (95% CI 1.1-2.9, P = 0.013). CONCLUSION: FM and reduced pressure pain thresholds aggregate in families, and FM coaggregates with major mood disorder in families. These findings have important clinical and theoretical implications, including the possibility that genetic factors are involved in the etiology of FM and in pain sensitivity. In addition, mood disorders and FM may share some of these inherited factors.

Ann Rheum Dis. 2004 Apr;63(4):450-452.

A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing.

Pimentel M, Wallace D, Hallegua D, Chow E, Kong Y, Park S, Lin HC.

BACKGROUND: An association between irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) has been found. OBJECTIVE: To compare the prevalence and test results for bacterial overgrowth between IBS and fibromyalgia. METHODS: Subjects with independent fibromyalgia and IBS were compared with controls in a double blind study. Participants completed a questionnaire, and a lactulose hydrogen breath test was used to determine the presence of SIBO. The prevalence of an abnormal breath test was compared between study participants. Hydrogen production on the breath test was compared between subjects with IBS and fibromyalgia. The somatic pain visual analogue score of subjects with fibromyalgia was compared with their degree of hydrogen production. RESULTS: 3/15 (20%) controls had an abnormal breath test compared with 93/111 (84%) subjects with IBS (p<0.01) and 42/42 (100%) with fibromyalgia (p<0.0001 v controls, p<0.05 v IBS). Subjects with fibromyalgia had higher hydrogen profiles (p<0.01), peak hydrogen (p<0.0001), and area under the curve (p<0.01) than subjects with IBS. This was not dependent on the higher prevalence of an abnormal breath test. The degree of somatic pain in fibromyalgia correlated significantly with the hydrogen level seen on the breath test (r = 0.42, p<0.01). CONCLUSIONS: An abnormal lactulose breath test is more common in fibromyalgia than IBS. In contrast with IBS, the degree of abnormality on breath test is greater in subjects with fibromyalgia and correlates with somatic pain.

J Psychosom Res. 2004 Feb;56(2):185-8.

Psychological aspects of fibromyalgia; Research vs. clinician impressions.

Sansone RA, Levengood JV, Sellbom M. Department of Internal Medicine, Kettering Medical Center, Kettering, OH, USA.

Objective: This study was designed to compare the psychological features of patients with fibromyalgia, as described in the research literature, with physicians' clinical impressions. Method: Using a survey method, physicians (n=44) and physicians-in-training (n=54) were polled regarding their clinical impressions of 18 psychological features, culled from the research literature, which are attributed to fibromyalgia patients. Results: Over 90% of respondents reported that fatigue, muscle tension, pain proneness, depression and anxiety were clinically associated with fibromyalgia patients "frequently" or "very frequently." The majority of respondents (52%) endorsed 10 of 18 items as occurring "frequently" or "very frequently." Conclusions: Physicians and physicians-in-training appear to observe in fibromyalgia patients over half of the psychological features identified in the research literature. For the remainder of items, we discuss possible explanations for the disparity.

Pain Med. 2004 Mar;5(1):33-41.

Comorbidity of fibromyalgia and posttraumatic stress disorder symptoms in a community sample of women.

Raphael KG, Janal MN, Nayak S.

OBJECTIVE: To test alternative explanations for the comorbidity between fibromyalgia (FM), a medically unexplained syndrome involving widespread pain, and posttraumatic stress disorder (PTSD). In contrast to a default "risk factor" hypothesis, tested hypotheses were that: A) The association is due to a sampling bias introduced by the study of care-seeking individuals; B) FM is an additive burden that strains coping resources when confronting life stress; and C) Arousal symptoms of PTSD and FM are confounded. DESIGN: Community-dwelling women in the New York/New Jersey metropolitan area (N=1,312) completed a telephone survey regarding FM-like symptoms prior to September 11, 2001. Approximately 6 months after the World Trade Center terrorist attacks, they again completed the survey, to which questions regarding PTSD symptoms were added. RESULTS: The odds of probable PTSD were more than three times greater in women with FM-like symptoms, both assessed after 9/11. The odds ratio was not reduced by controlling for FM-like symptoms before 9/11 or for the potentially confounded symptoms of PTSD specifically related to arousal. CONCLUSIONS: These findings lead us to reject alternate explanations for the comorbidity between FM and PTSD. Speculations that FM and PTSD share psychobiological risk factors remain plausible.

Psychol Med. 2004 Feb;34(2):363-8.

Post-traumatic stress disorder among patients with chronic pain and chronic fatigue.

Roy-Byrne P, Smith WR, Goldberg J, Afari N, Buchwald D. Department of Psychiatry and Behavioral Science, University of Washington, Seattle, WA, USA.

BACKGROUND: Fibromyalgia (FM), a chronic pain condition of unknown aetiology often develops following a traumatic event. FM has been associated with post-traumatic stress disorder (PTSD) and major depression disorder (MDD). METHOD: Patients seen in a referral clinic (N=571) were evaluated for FM and chronic fatigue syndrome (CFS) criteria. Patients completed questionnaires, and underwent a physical examination and a structured psychiatric evaluation. Critical components of the diagnostic criteria of FM (tender points and diffuse pain) and CFS (persistent debilitating fatigue and four of eight associated symptoms) were examined

for their relationship with PTSD. RESULTS: The prevalence of lifetime PTSD was 20% and lifetime MDD was 42%. Patients who had both tender points and diffuse pain had a higher prevalence of PTSD (OR=3.4, 95% CI 2.0-5.8) compared with those who had neither of these FM criteria. Stratification by MDD and adjustment for sociodemographic factors and chronic fatigue revealed that the association of PTSD with FM criteria was confined to those with MDD. Patients with MDD who met both components of the FM criteria had a threefold increase in the prevalence of PTSD (95% CI 1.5-7.1); conversely, FM patients without MDD showed no increase in PTSD (OR=1.3, 95% CI 0.5-3.2). The components of the CFS criteria were not significantly associated with PTSD. CONCLUSION: Optimal clinical care for patients with FM should include an assessment of trauma in general, and PTSD in particular. This study highlights the importance of considering co-morbid MDD as an effect modifier in analyses that explore PTSD in patients with FM.

J Rheumatol. 2004 Mar;31(3):598-600.

Clues to pathogenesis of fibromyalgia in patients with sickle cell disease.

Schlesinger N. schlesna@umdnj.edu

OBJECTIVE: To investigate the association between sickle cell disease (SCD) and fibromyalgia (FM). METHODS: Nine patients with SCD for whom a rheumatology consult was requested were assessed for FM by retrospective chart review. Eleven inpatients with other forms of anemia referred for rheumatology consult were also assessed for FM. RESULTS: Eight of 9 patients with SCD fulfilled classification criteria for FM compared to one of 11 patients without SCD (p < 0.001). CONCLUSION: Awareness of the high frequency of FM in SCD can improve treatment of sickle cell crisis. Some pain that is labeled as sickle cell crisis pain may be due to FM, and may improve with tender point injections.

Rheumatol Int. 2004 Feb 21 [Epub ahead of print]

Auditory event-related brain potentials in fibromyalgia syndrome.

Alanoglu E, Ulas UH, Ozdag F, Odabasi Z, Cakci A, Vural O. Physical Therapy and Rehabilitation Department, Social Security Hospital of Ankara, Diskapi, Ankara, Turkey.

OBJECTIVE. The aim of this study was to investigate cognitive functions using auditory event-related brain potentials (ERP) in fibromyalgia syndrome (FMS). METHODS. The P300 component of ERP was studied in 36 female FMS patients and 22 control subjects. The short form 36 (SF-36) medical outcome study was used to determine quality of life. Number of tender points and disease duration were noted. Cognitive functions were evaluated with P300. RESULTS. The symptoms were discrepant in FMS ( P<0.001). The scores of the eight SF-36 subgroups in FMS patients were significantly lower than in the control group ( P<0.001). Fibromyalgia syndrome patients had prolonged latency and reduced amplitude of P300 ( P<0.001). No correlation was found between the subgroups of SF-36, tender point count, disease duration, and P300. CONCLUSION. The results of our study reveal that FMS affects quality of life and dysfunction in cognitive abilities can be determined by brain event-related potentials.

Med Hypotheses. 2004 Mar;62(3):420-4.

Stress and dopamine: implications for the pathophysiology of chronic widespread pain.

Wood PB. Department of Family Medicine, LSU Health Science Center - Shreveport, 1501 Kings Highway Shreveport, LA 71103, USA.

Fibromyalgia has been called a "stress-related disorder" due to the onset and exacerbation of symptoms in the context of stressful events. Evidence suggests that inhibition of tonic pain is mediated by activation of mesolimbic dopamine neurons, arising from the cell bodies of the ventral tegmental area and projecting to the nucleus accumbens. This pain-suppression system is activated by acute stress, via the release of endogenous opioids and substance P within the ventral tegmental area. However, prolonged exposure to unavoidable stress produces both reduction of dopamine output in the nucleus accumbens and development of persistent hyperalgesia. It is proposed that a stress-related reduction of dopaminergic tone within the nucleus accumbens contributes to the development of hyperalgesia in the context of chronic stress and thus plays a role in the pathogenesis of fibromyalgia. A stress-related dysfunction of mesolimbic dopaminergic activity might serve as the basis for other fibromyalgia-associated phenomena as well.

Ann Rheum Dis. 2004 Mar;63(3):290-6.

Fibromyalgia: a randomised, controlled trial of a treatment programme based on self management.

Cedraschi C, Desmeules J, Rapiti E, Baumgartner E, Cohen P, Finckh A, Allaz AF, Vischer TL. Christine.Cedraschi@hcuge.ch

OBJECTIVE: To evaluate the efficacy of a treatment programme for patients with fibromyalgia (FM) based on self management, using pool exercises and education. METHODS: Randomised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme; 164 patients with FM were allocated to an immediate 6 week programme (n = 84) or to a waiting list control group (n = 80). The main outcomes were changes in quality of life, functional consequences, patient satisfaction and pain, using a combination of patient questionnaires and clinical examinations. The questionnaires included the Fibromyalgia Impact Questionnaire (FIQ), Psychological General Well-Being (PGWB) index, regional pain score diagrams, and patient satisfaction measures. RESULTS: 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations. Six months after programme completion, significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ (total score p = 0.025; fatigue p = 0.003; depression p = 0.031) and PGWB (total score p = 0.032; anxiety p = 0.011; vitality p = 0.013,). All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups; between-group differences were statistically significant for "control of symptoms", "psychosocial factors", and "physical therapy" No change in pain was seen. CONCLUSION: A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment. These improvements are sustained for at least 6 months after programme completion.

Ann Rheum Dis. 2004 Mar;63(3):245-51.

Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres.

Sprott H, Salemi S, Gay RE, Bradley LA, Alarcon GS, Oh SJ, Michel BA, Gay S. haiko.sprott@usz.ch

OBJECTIVE: To determine whether there is evidence of increased DNA fragmentation and ultrastructural changes in muscle tissue of patients with fibromyalgia (FM) compared with healthy controls. METHODS: Muscle tissues from 10 community residents with FM and 10 age and sex matched healthy controls were examined "blindly" for the presence of DNA fragmentation by two different methods: terminal deoxynucleotidyl transferase (TdT) staining (TUNEL) and the FragEL-Klenow DNA fragmentation detection kit. Ultrastructural analysis of tissue was performed by electron microscopy. RESULTS: DNA fragmentation was detected by both methods in 55.4 (SEM 2.5)% of the nuclei in muscle tissue of patients with FM compared with 16.1 (4.1)% (p<0.001) of the nuclei in healthy controls. Contrary to expectation, no typical features of apoptosis could be detected by electron microscopy. The myofibres and actin filaments were disorganised and lipofuscin bodies were seen; glycogen and lipid accumulation were also found. The number of mitochondria was significantly lower in patients with FM than in controls and seemed to be morphologically altered. CONCLUSION: The ultrastructural changes described suggest that patients with FM are characterised by abnormalities in muscle tissue that include increased DNA fragmentation and changes in the number and size of mitochondria. These cellular changes are not signs of apoptosis. Persistent focal contractions in muscle may contribute to ultrastructural tissue abnormalities as well as to the induction and/or chronicity of nociceptive transmission from muscle to the central nervous system.

Arthritis Rheum. 2004 Feb 15;51(1):9-13.

Treatment of fibromyalgia with cyclobenzaprine: A meta-analysis.

Tofferi JK, Jackson JL, O'Malley PG.

OBJECTIVE: To systematically review the effectiveness of cyclobenzaprine in the treatment of fibromyalgia. METHODS: Articles describing randomized, placebo-controlled trials of cyclobenzaprine in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted. RESULTS: Five randomized, placebo-controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6-5.6) with a pooled risk difference of

0.21 (95% CI 0.09-0.34), which calculates to 4.8 (95% CI 3.0-11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time. CONCLUSION: Cyclobenzaprine-treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

Curr Opin Rheumatol. 2004 Mar;16(2):157-63.

Fibromyalgia pain: do we know the source?

Staud R. staudr@ufl.edu

PURPOSE OF REVIEW: Fibromyalgia Syndrome (FMS) is a chronic pain condition of unknown origin. Multiple abnormalities have been described, including peripheral tissue and central nervous system changes. The relation of these mechanisms, however, is likely bidirectional. FMS pain clearly depends on peripheral nociceptive input as well as abnormal central pain processing. This review will focus on the role of peripheral nociceptive input for pain in FMS. RECENT FINDINGS: There is strong evidence for abnormal central pain processing in FMS. Sensitized spinal cord neurons in the dorsal horn are responsible for augmented pain processing of nociceptive signals from the periphery. In addition, glial activation, possibly by cytokines and excitatory amino acids may play a role in the initiation and perpetuation of this sensitized state. SUMMARY: Nociceptive input clearly plays an important role in FMS. Acute or repetitive tissue injury has been associated with FMS pain. Cytokines related to such injuries may be responsible for long-term activation of spinal cord glia and dorsal horn neurons, thus resulting in central sensitization. A better understanding of these important neuro-immune interactions may provide relevant insights into future effective therapies.

J Rheumatol. 2004 Feb;31(2):379-89.

Aspects of diurnal rhythmicity in pain, stiffness, and fatigue in patients with fibromyalgia.

Bellamy N, Sothern RB, Campbell J. Faculty of Health Sciences, The University of Queensland, Brisbane, Australia.

OBJECTIVE: To determine diurnal rhythm characteristics of pain, stiffness, and fatigue in self-ratings performed by patients with fibromyalgia (FM). METHODS: Twenty-one women with FM made self-measurements of pain, stiffness, and fatigue on 100 mm horizontal visual analog scales at 6 prespecified timepoints at home for 10 consecutive days. Linear and multiple regressions were performed on the original data and the 24-hour means vs FM classifiers (age, disease duration, tender points, dolorimetry score, Fibromyalgia Impact Questionnaire score), respectively. Data were analyzed for 24-hour and 7-day time-effects by ANOVA and for diurnal and weekly rhythms by the cosinor technique. RESULTS: Individual ratings for pain, stiffness, and fatigue correlated highly with each other throughout the day and over the days of the week. Of the FM classifiers, dolorimetry score was found to be inversely related to the pain, stiffness, and fatigue scores. For the group of subjects with a low dolorimetry score (< 2.25 kg), a significant diurnal rhythm was found in each self-rated variable, with greater pain, stiffness, and fatigue observed in the morning and least in the late afternoon. No rhythm in pain or stiffness was observed in those subjects with a higher threshold for pain (dolorimetry score > 2.25 kg), while fatigue showed the same significant diurnal pattern as in the first group. For the group as a whole, the possible presence of a weekly variation was found with ratings for pain, stiffness, and fatigue higher on Sunday and Monday and lower on Friday. CONCLUSION: Ratings of pain, stiffness, and fatigue in FM are significantly correlated, and show diurnal and possibly weekly rhythmicity, especially when pain threshold is low (dolorimetry score < 2.25 kg), and are thus predictive of each other over these time spans. This has important implications for scheduling activities of daily living, for measurement in clinical trials, and possibly for timing the administration of medications.

J Rheumatol. 2004 Feb;31(2):364-78.

Functional imaging of pain in patients with primary fibromyalgia.

Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. cookdb@njneuromed.org

OBJECTIVE: To examine the function of the nociceptive system in patients with fibromyalgia (FM) using functional magnetic resonance imaging (fMRI). METHODS: Two groups of women, 9 with FM and 9 pain-free, volunteered to participate. In Experiment 1, we assessed psychophysical responses to painful stimuli and prepared participants for fMRI testing. For Experiment 2, subjects underwent fMRI scanning while receiving painful and nonpainful heat stimuli. Conventional and functional MR images were acquired using a 1.5 T MR scanner. Scanning occurred over 5 conditions. Condition 1 served as a practice session (no stimuli). Conditions 2 and 5 consisted of nonpainful warm stimuli. Conditions 3 and 4 consisted of an absolute thermal pain stimulus (47 degrees C) and a perceptually equivalent pain stimulus delivered in counterbalanced order. RESULTS: Experiment 1 indicated that subjects with FM were significantly more sensitive to experimental heat pain than controls (p < 0.001). In Experiment 2, fMRI data indicated that the FM group exhibited greater activity than controls over multiple brain regions in response to both nonpainful and painful stimuli (p < 0.01). Specifically, in response to nonpainful warm stimuli, FM subjects had significantly greater activity than controls in prefrontal, supplemental motor, insular, and anterior cingulate cortices (p < 0.01). In response to painful stimuli, FM subjects had greater activity in the contralateral insular cortex (p < 0.01). Data from the practice session indicated brain activity in pain-relevant areas for the FM group but not for controls. CONCLUSION: Our results provide further evidence for a physiological explanation for FM pain.

Rheumatology (Oxford). 2004 Jan 20

Improved clinical status in fibromyalgia patients treated with individualized homeopathic remedies versus placebo.

Bell IR, Lewis II DA, Brooks AJ, Schwartz GE, Lewis SE, Walsh BT, Baldwin CM.

OBJECTIVE: To assess the efficacy of individualized classical homeopathy in the treatment of fibromyalgia. METHODS: This study was a double-blind, randomized, parallel-group, placebo-controlled trial of homeopathy. Community-recruited persons (N = 62) with physician-confirmed fibromyalgia (mean age 49 yr, s.d. 10 yr, 94% women) were treated in a homeopathic private practice setting. Participants were randomized to receive oral daily liquid LM (1/50 000) potencies with an individually chosen homeopathic remedy or an indistinguishable placebo. Homeopathic visits involved joint interviews and concurrence on remedy selection by two experienced homeopaths, at baseline, 2 months and 4 months (prior to a subsequent optional crossover phase of the study which is reported elsewhere). Tender point count and tender point pain on examination by a medical assessor uninvolved in providing care, self-rating scales on fibromyalgia-related quality of life, pain, mood and global health at baseline and 3 months, were the primary clinical outcome measures for this report. RESULTS: Fifty-three people completed the treatment protocol. Participants on active treatment showed significantly greater improvements in tender point count and tender point pain, quality of life, global health and a trend toward less depression compared with those on placebo. CONCLUSIONS: This study replicates and extends a previous 1-month placebo-controlled crossover study in

fibromyalgia that pre-screened for only one homeopathic remedy. Using a broad selection of remedies and the flexible LM dose (1/50 000 dilution factor) series, the present study demonstrated that individualized homeopathy is significantly better than placebo in lessening tender point pain and improving the quality of life and global health of persons with fibromyalgia.

Pain. 2004 Jan;107(1-2):7-15.

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

Banic B, Petersen-Felix S, Andersen OK, Radanov BP, Villiger PM, Arendt-Nielsen L, Curatolo

M.

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.

Rheumatol Int. 2003 Dec 20

Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder?

Bagis S, Tamer L, Sahin G, Bilgin R, Guler H, Ercan B, Erdogan C.

The role of free radicals in fibromyalgia is controversial. In this study, 85 female patients with primary fibromyalgia and 80 age-, height-, and weight-matched healthy women were evaluated for oxidant/antioxidant balance. Malondialdehyde is a toxic metabolite of lipid peroxidation used as a marker of free radical damage. Superoxide dismutase is an intracellular antioxidant enzyme and shows antioxidant capacity. Pain was assessed by visual analog scale. Tender points were assessed by palpation. Age, smoking, body mass index (BMI), and duration of disease were also recorded. Malondialdehyde levels were significantly higher and superoxide dismutase levels significantly lower in fibromyalgic patients than controls. Age, BMI, smoking, and duration of disease did not affect these parameters. We found no correlation between pain and number of tender points. In conclusion, oxidant/antioxidant balances were changed in fibromyalgia. Increased free radical levels may be responsible for the development of

fibromyalgia. These findings may support the hypothesis of fibromyalgia as an oxidative disorder.

Schmerz. 2003 Dec;17(6):399-404.

[Psychosomatic aspects in the diagnosis and treatment of fibromyalgia]

[Article in German] Blumenstiel K, Eich W. Abteilung fur Allgemeine Klinische und Psychosomatische Medizin, Medizinische Klaus_Blumenstiel@med.uni-heidelberg.de

The fibromyalgia syndrome (FMS) is a chronic pain condition of the musculoskeletal system defined by criteria of the American College of Rheumatology in 1990. Despite this definition, etiology and pathogenesis of FMS are still unknown, and consequently the therapy aims mainly at relieving symptoms. The favourite hypothesis is a multietiological concept including genetic, central nervous, muscular, and psychological issues. This article focuses on current psychological aspects as to etiology, process of chronification, and therapy of FMS. Regarding etiology there are diverging hypotheses rather than a general agreement, e.g. specific personality traits, traumatic events, psychodynamic explanations on the basis of a depressive conflict, or the subsumption under somatoform disorders. However, psychological aspects are evident to influence the course and treatment of FMS. In the chronification process behavioural aspects like avoidance behaviour with subsequent physical impairment, attitudes towards subjective theories of illness and therapeutic options, social factors like effects on work, interpersonal conditioning, and coping strategies play an important role. Therapeutic options of FMS comprise exercise, drugs, and psychotherapy. An integrated approach combining these options, a sustainable doctor-patient relationship, and a continuous support of the patient seem to be beneficial.

Schmerz. 2003 Dec;17(6):437-40. [What's new in the therapy of fibromyalgia?] [Article in German] Spath M. Friedrich-Baur-Institut, Ludwig-Maximilians-Universitat Munchen. michael.spaeth@lrz.uni- muenchen.de

Modern management of fibromyalgia (FM) requires a holistic approach, which includes nonpharmacologic strategies (both exercise and behavioral strategies) and pharmacologic treatment. Despite only partial effects in some patients, tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal antiinflammatory drugs, analgesics and opioids are in use. The use of antiepileptic drugs and antispasticity agents is mainly supported by anecdotal data. Three other classes of agents are currently thought to have useful potentials. N-methyl-D-aspartate-(NMDA-)mediated neurotransmission may play an important role in mediating windup and related phenomena in pain pathways. Recent studies have demonstrated that NMDA receptor antagonists improve pain symptoms in FM. But a poor side effect profile represents a significant problem. Cerebrospinal fluid substance P concentrations are significantly elevated in FM patients, but the analgesic potential of neurokinin-1 (NK1) receptor antagonists did not meet early expectations. Tropisetron, a 5-HT3 receptor antagonist, was tested in a multicenter, double-blind, randomized, placebo-controlled trial including 403 patients. In those receiving 5 mg tropisetron, 39.2% fulfilled the response criterion (pain reduction 35%) as compared to 26.2% in the placebo group (p=0.033). On 10 and 15 mg, the responder rates were smaller and statistically not significant. A total of 78 responders to therapy were followed up for 12 months. After the end of treatment, pain intensity rose within one month in all 4 groups. Patients having received 5 or 10 mg showed a less pronounced increase in pain. In addition, even 12 months after stopping treatment, pain was still markedly below baseline levels in the 5 and 10 mg groups.

OLDER

ARTHRITIS & RHEUMATISM Vol. 46, No. 5, May 2002, pp 1333-1343

Functional Magnetic Resonance Imaging Evidence of Augmented Pain Processing in Fibromyalgia

Richard H. Gracely, Frank Petzke Julie M. Wolf and Daniel J. Clauw Objective. To use functional magnetic resonance imaging (fMRI) to evaluate the pattern of cerebral activation during the application of painful pressure and determine whether this pattern is augmented in patients with fibromyalgia (FM) compared with controls. Methods. Pressure was applied to the left thumbnail beds of 16 right-handed patients with FM and 16 right-handed matched controls. Each FM patient underwent fMRI while moderately painful pressure was being applied. The functional activation patterns in FM patients were compared with those in controls, who were tested under 2 conditions: the "stimulus pressure control" condition, during which they received an amount of pressure similar to that delivered to patients, and the "subjective pain control" condition, during which the intensity of stimulation was increased to deliver a subjective level of pain similar to that experienced by patients. Results. Stimulation with adequate pressure to cause similar pain in both groups resulted in 19 regions of increased regional cerebral blood flow in healthy controls and 12 significant regions in patients. Increased fMRI signal occurred in 7 regions common to both groups, and decreased signal was observed in 1 common region. In contrast, stimulation of controls with the same amount of pressure that caused pain in patients resulted in only 2 regions of increased signal, neither of which coincided with a region of activation in patients. Statistical comparison of the patient and control groups receiving similar stimulus pressures revealed 13 regions of greater activation in the patient group. In contrast, similar stimulus pressures produced only 1 region of greater activation in the control group. Conclusion. The fact that comparable subjectively painful conditions resulted in activation patterns that were similar in patients and controls, whereas similar pressures resulted in no common regions of activation and greater effects in patients, supports the hypothesis that FM is characterized by cortical or subcortical augmentation of pain processing.

Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.

Clauw DJ; Chrousos GP Neuroimmunomodulation, 1997 May, 4:3, 134-53

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause. This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses.

BioMed Central - Factors explaining variance in perceived pain in women with fibromyalgia

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Musculoskeletal

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Publishing peer-reviewed

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Factors explaining variance in perceived pain in women with fibromyalgia

Eva Albertsen Malt1, Snorri Olafsson2, Anders Lund1

and Holger Ursin3

¹Department of Psychiatry, University of Bergen Haukeland University Hospital, N-5022 Bergen, Norway ²Department of Internal Medicine, University of Bergen

Haukeland University Hospital, N-5022 Bergen, Norway ³Department of Biological And Medical Psychology, Division of Physiological Psychology University of Bergen, N-5022 Bergen, Norway

BMC Musculoskeletal Disorders 2002 3: 12

This article is available from: http://www.biomedcentral.com/1471-2474/3/12

Accepted 25 Apr 2002

Published 25 Apr 2002

2002 Malt et al; licensee BioMed Central Ltd. Verbatim copying and redistribution of this article are permitted in any medium for any purpose, provided this notice is preserved

along with the article's original URL.

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BioMed Central - Factors explaining variance in perceived pain in women with fibromyalgia

Conclusion

Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients.

http://www.biomedcentral.com/1471-2474/3/12 (3 of 30) [9/12/2002 10:13:40 PM]

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Last Updated: November 15, 2001 ^{Differentials}

Synonyms and related keywords: fibromyositis, fibrositis, idiopathic myalgia, interstitial ^Workup myofibrositis, muscular hardening, muscular rheumatism,musculorheumatism, ^Treatment myofibrositis, myogelosis, myositism, nodular rheumatism,nonarticular rheumatism, ^Medication

polymyalgia rheumatica, rheumatic muscle callus, rheumatic muscle hardening, rheumatic ^Follow-up myalgia, rheumatic pain modulation disorder, tension myalgia ^Bibliography Click for related images. Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Bibliography

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Author: Regina P Gilliland, MD, Medical Director, Health Link Functional ^{Cervical Disc} Rehabilitation, Department of Internal Medicine; Division of Rehab Medicine, ^Disease Baptist Medical Center

Cervical Regina P Gilliland, MD, is a member of the following medical societies: American Myofascial Pain Academy of Physical Medicine and Rehabilitation, Medical Association of the _{Cervical Sprain} State of Alabama, and Southern Medical Association _{and Strain}

Editor(s): Martin K Childers, DO, Associate Professor, Department of Physical Medicine and Rehabilitation, University of Missouri School of Medicine; Chronic Pain Syndrome

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Patrick M Foye, MD, FAAPMR, FAAEM, Assistant Professor, Department of _{Complex Regional} Physical Medicine and Rehabilitation, University of Medicine and Dentistry of _{Pain Syndromes} New Jersey; Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady Hypothyroid of Lourdes Medical Center; and Consuelo T Lorenzo, MD, Consulting Staff, ^Myopathy Department of Physical Medicine and Rehabilitation, Alegent Health Care, _Lumbar Immanuel Rehabilitation Center _{Degenerative Disc}

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Background: Fibromyalgia is a complex disorder defined only recently, but it is

Mechanical Low

not a recently discovered disorder. Descriptions have been found in the medical _{Back Pain} literature as far back as the early 17th century. Many physicians prefer not to deal with patients who have this complicated disorder and question the actual Meralgia existence of the disorder. In the past, poor recognition and lack of treatment for ^Paresthetica this disorder could be explained by a lack of meaningful research. Today _{Myofascial Pain}

http://www.emedicine.com/pmr/topic47.htm 06/14/2003 11:15:59 PM eMedicine - Fibromyalgia : Article by Regina P Gilliland, MD Page 27

Teitelbaum J: For physicians. In: From Fatigued to Fantastic! Avery Publishing; 1995:93-115.

Travell JG, Simons DG: In: Myofascial Pain and Dysfunction: The Trigger Point Manual.

Baltimore: Lippincott Williams & Wilkins; 1983. UCLA Sleep Research Society: Basics of Sleep Behavior: What is Sleep. 1997; Available at: http://www.sleephomepages.org/sleepsyllabus.[Full Text].

Vecchiet L, Giamberardino MA: Referred Pain: Clinical Significance, Pathophysiology, and

Treatment. Physical Medicine and Rehabilitation Clinics of North America 1997; 8: 119-136. Wolfe F, Smythe HA, Yunus MB, et al: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990 Feb; 33(2): 160-72[Medline].

Yunus MB: Fibromyalgia Syndrome: Clinical Features and Spectrum. J Musculoskelet Pain 1994;

2: 5-21.

Zohn DA: Relationship of Joint Dysfunction and Soft-Tissue Problems. Phys Med Rehabil Clin North Am 1997; 8: 69-86.

NOTE:

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER

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Year 2000 (Some 1999, 2000) Abstracts

The British Journal of Rheumatology, Vol 34, 925-931

Muscle strength, voluntary activation and cross-sectional muscle area in patients with fibromyalgia

J Norregaard, PM Bulow, P Vestergaard-Poulsen, C Thomsen and B Danneskiold-Samoe Department of Rheumatology, Frederiksberg Hospital, Copenhagen, Denmark.

The objectives were to determine whether the low muscle strength in fibromyalgia is due to lack of exertion and to determine the relation between strength and muscle area. Secondarily we examined the voluntary muscle strength of the different muscles of the leg. The twitch interpolation technique was used to estimate the degree of central activation and the 'true' quadriceps muscle strength. Muscle cross- sectional area was determined with magnetic resonance imaging (MRI). The estimated 'true' muscle strength was 91 Nm (S.D. = 34 Nm) in 15 fibromyalgia patients compared with 125 Nm (28 Nm) in 14 healthy controls (P < 0.02). The 'true' strength divided