1. Unique Identifier 20023806
Author Gordon DA
Institution University of Toronto, Ontario, Canada.
Title Chronic widespread pain as a medico-legal issue.
Source Baillieres Best Pract Res Clin Rheumatol 1999 Sep;13(3): p531-43
ISSN 1521-6942
Abstract

A systematic approach to the determination of disability in persons with chronic widespread pain is based on a careful history, examination for tender points, and special investigations to establish a firm diagnosis. Further assessment requires determination of subjective and objective measures of impairment. The causes of fibromyalgia are multifactorial and understanding them requires an appreciation of the role of physical or psychological trauma, and associated medical and psychosocial factors. Despite the presence of disability risk factors, most patients with fibromyalgia maintain a good range of normal daily activities and continue working.

2. Unique Identifier 20023797
Author Russell IJ
Institution University of Texas Health Science Center, San Antonio, Texas 78284-7868, USA.
Title Is fibromyalgia a distinct clinical entity? The clinical investigator's evidence.
Source Baillieres Best Pract Res Clin Rheumatol 1999 Sep;13(3): p445-54
ISSN 1521-6942
Abstract

SUBJECTIVE: Chronic widespread pain with multiple tender points (fibromyalgia syndrome) is a common clinical presentation. Criteria for inclusion of fibromyalgia patients into research studies have led to a medical model which integrates symptoms, signs, epidemiology, pathogenesis, responses to treatment, and prognosis. Controversy regarding fibromyalgia relates mostly to issues of compensation.
THEORETICAL: The diagnosis of fibromyalgia has been challenged as an inappropriate extraction from an epidemiological continuum of subjective discomfort. There are many conditions in which normally distributed measures exhibit distinctly unique outcomes at their extremes.
OBJECTIVE: Since fibromyalgia patients exhibit lowered pain thresholds, the process of nociception was studied. Samples of fibromyalgia urine, blood, and spinal fluid disclosed abnormalities consistent with a biomedical model of failed neuroregulatory inhibition, altered nociception, central sensitization, and allodynia. All three views support fibromyalgia as a distinct clinical syndrome deserving of informed medical care and continued research to better understand chronic widespread pain.

3.Unique Identifier 95214027
Author Wolfe F; Ross K; Anderson J; Russell IJ
Institution Arthritis Research and Clinical Centers (St. Francis Research Institute, Wichita, KS 67214.
Title Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms.
Source J Rheumatol 1995 Jan;22(1): p151-6
ISSN 0315-162X
Abstract

OBJECTIVE. To investigate relationships between sex, pain threshold and fibromyalgia (FM) symptoms in the general population.
METHODS. Data were obtained from a randomized populations survey of 3,006 persons in Wichita, KS and a subsample of 391 who completed a detailed interview and had an examination. Tender point counts, dolorimetry scores, clinical and psychological variables were measured.
RESULTS. Dolorimetry scores were 2.04 kg/cm (1.42-2.66) lower in women than men, and women were almost 10 times more likely to have 11 tender points [OR 9.6 (2.00-46.3)] than men. Women are also more likely to have FM symptoms than men: "Pain all over," [OR 3.94 (1.34-11.38)], sleep disturbance [OR 3.06 (1.45-6.46)], fatigue [OR 4.52 (2.03-10.09)], and irritable bowel syndrome [OR 5.23 (1.83-14.96)]. Tender point counts are more correlated with FM symptoms than dolorimetry scores.
CONCLUSION. Symptoms of FM are correlated with pain threshold in the general population, but tender point counts correlate better than dolorimetry. These 2 measures of pain threshold assay different but overlapping factors. Pain threshold is lower in women; and women have more FM symptoms. Decreased pain threshold correlates with all of the symptoms of FM, even in those who do not meet criteria for the syndrome. This suggests that decreased pain threshold, as measured by the tender point counts, is an intrinsically important aspect of patient distress, regardless of the extent and kind of concomitant disease; and that much can be learned about patients by employing this examination.

4. Unique Identifier 92390724
Author Malmberg AB; Yaksh TL
Institution Department of Anesthesiology, University of California-San Diego, La Jolla 92093-0818.
Title Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase Inhibition.
Source Science 1992 Aug 28;257(5074): p1276-9
ISSN 0036-8075
Abstract

A inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in the periphery is commonly accepted as the primary mechanism by which these agents produce a selective attenuation of pain (analgesia). NSAIDs are now shown to exert a direct spinal action by blocking the excessive sensitivity to pain (hyperalgesia) induced by the activation of spinal glutamate and substance P receptors. These findings demonstrate that the analgesic effects of NSAIDs can be dissociated from their anti-inflammatory actions. Spinal prostanoids are thus critical for the augmented processing of pain information at the spinal level.

5. Author Hoheisel U, Mense S, Ratkai M.
Title Effects of spinal cord superfusion with substance P on the excitability of rat dorsal horn neurons processing input from deep tissues.
Source J Musculoske Pain 3(3) : 23-43, 1998.
Abstract

OBJECTIVES: Starting from the clinical findings that in fibromyalgia patients the concentration of substance P (SP) in the cerebrospinal fluid is increased, the study aimed at determining the influence of intrathecally administratered SP on the excitability of dorsal horn neurons.
METHODS: In anesthetized rats, the discharges of single dorsal horn neurons in response to electrical stimulation of peripheral nerves and mechanical stimulation of receptive fields (Rfs) were recorded. Only those neurons were studied that had excitatory input from non-proprioceptive receptors in deep tissues. The influence of SP on the excitability of the cells was determined by superfusing the spinal cord with SP at defined concentrations.
RESULTS: The main effects of SP were : 1. Increase in the number of peripheral nerves and-or afferent fiber types that were effective in driving the dorsal horn neurons. 2. Increase in the size or number of mechnosensitive Rfs in nociceptive neurons. 3. Loss of an existing response to peripheral input. The SP-induced effects or number of mechnosensitive Rfs in nociceptive neurons. 3. Loss of an existing response to peripheral input. The SP-induced effects were dose-dependent, the threshold concentration in the superfusate being 1-10 µM. Intracellular recordings showed that in the presence of SP subthreshold excitatory postsynaptic potentials became suprathreshold.
CONCLUSIONS: The results demonstrate that intrathecal SP affects dorsal horn neurons in different ways. One important action of the neuropeptide is to unmask synaptic connections in the dorsal horn. The data are compatible with the assumption that SP is involved in neuroplastic changes in the dorsal horn. The increase in RF size in nociceptive cells may be a possible mechanism for hyperalgesia in patients with deep pain.

6. Author Russell J et al.
Title Cerebrospinal Fluid (CSF) Substance P (SP) in Fibromyalgia (FMS): Changes in CSP SP Over Time, Parallel Changes in Clinical Activity.
Source Arthritis & Rheumatism, Abstract Supplement, Vol. 41, #9, September 1998.

7. Unique Identifier 20385029
Author Larson AA; Giovengo SL; Russell IJ; Michalek JE
Institution Graduate Program in Neuroscience, 295 Animal Science/Veterinary Medicine Building, University of Minnesota, 1988 Fitch Avenue, St. Paul, MN 55108, USA. larso011@tc.umn.edu.
Title Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways.
Source Pain 2000 Aug;87(2): p201-11
ISSN 0304-3959
Abstract

Substance P (SP), a putative nociceptive transmitter, is increased in the CSF of patients with fibromyalgia syndrome (FMS). Because excitatory amino acids (EAAs) also appear to transmit pain, we hypothesized that CSF EAAs may be similarly involved in this syndrome. We found that the mean concentrations of most amino acids in the CSF did not differ amongst groups of subjects with primary FMS (PFMS), fibromyalgia associated with other conditions (SFMS), other painful conditions not exhibiting fibromyalgia (OTHER) or age-matched, healthy normal controls (HNC). However, in SFMS patients, individual measures of pain intensity, determined using an examination-based measure of pain intensity, the tender point index (TPI), covaried with their respective concentrations of glutamine and asparagine, metabolites of glutamate and aspartate, respectively. This suggests that re-uptake and biotransformation mask pain-related increases in EAAs. Individual concentrations of glycine and taurine also correlated with their respective TPI values in patients with PFMS. While taurine is affected by a variety of excitatory manipulations, glycine is an inhibitory transmitter as well as a positive modulator of the N-methyl-D-asparate (NMDA) receptor. In both PFMS and SFMS patients, TPI covaried with arginine, the precursor to nitric oxide (NO), whose concentrations, in turn, correlated with those of citrulline, a byproduct of NO synthesis. These events predict involvement of NO, a potent signaling molecule thought to be involved in pain processing. Together these metabolic changes that covary with the intensity of pain in patients with FMS may reflect increased EAA release and a positive modulation of NMDA receptors by glycine, perhaps resulting in enhanced synthesis of NO.

8. Unique Identifier 99334418
Author Giovengo SL; Russell IJ; Larson AA
Institution Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108, USA.
Title Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia.
Source J Rheumatol 1999 Jul;26(7): p1564-9
ISSN 0315-162X
Abstract

OBJECTIVE: To determine whether there is a difference in the concentration of nerve growth factor (NGF) in the cerebrospinal fluid (CSF) from patients diagnosed with primary fibromyalgia syndrome (FM), fibromyalgia associated with other secondary conditions (SFM), patients with other painful conditions but lacking fibromyalgia (OTHER), and healthy controls.
METHODS: The clinical measures of pain threshold included the tender point index, a measure of pain threshold intensity measured by digital pressure, and the average pain threshold measured by dolorimetry. Concentrations of NGF in the CSF were measured using a 2 site enzyme immunoassay.
RESULTS: The mean (+/- SEM) concentration of NGF measured in patients with FM was significantly increased (41.8 +/- 12.7 pg/ml) compared to controls (9.1 +/- 4.1 pg/ml), but with large variability. Concentrations of NGF is SFM (8.9 +/- 4.4 pg/ml) and OTHER (16.2 +/- 8.4 pg/ml) were not elevated compared to controls.
CONCLUSION: The findings of increased concentrations of NGF in patients with FM suggest a central mechanism, involving abnormalities in neuropeptides such as NGF, may be a factor in the pathogenesis of FM.

9. Unique Identifier 20043619
Author Leventhal LJ
Institution Graduate Hospital, Philadelphia, PA 19146-1497, USA.
Title Management of fibromyalgia.
Source Ann Intern Med 1999 Dec 7;131(11): p850-8
ISSN 0003-4819

10. Unique Identifier 96216521
Author Wigers SH; Stiles TC; Vogel PA
Institution Department of Physical Medicine and Rehabilitation, University Hospital of Trondheim, Norway.
Title Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study.
Source Scand J Rheumatol 1996;25(2): p77-86
ISSN 0300-9742
Abstract

To determine and compare short- and long-term effects of aerobic exercise (AE), stress management treatment (SMT), and treatment-as-usual (TAU) in fibromyalgia, 60 patients were randomized to 14 weeks of treatment by either AE, SMT or TAU. Outcome measures at baseline, midway through treatment, at treatment completion, and at 4 year follow up included a patient made drawing of pain distribution, dolorimetry of tender points, ergometer cycle test, global subjective improvement, and VAS registrations of: pain, disturbed sleep, lack of energy, and depression. Both AE and SMT showed positive short-term effects. AE was the overall most effective treatment, despite being subject to the most sceptical patient attitude prior to the study. At follow up, there were no obvious group differences in symptom severity, which for AE seemed to be due to a considerable compliance problem.

11. Unique Identifier 20023804
Author Sim J; Adams N
Institution Primary Care Sciences Research Centre, Keele University, Staffordshire, UK.
Title Physical and other non-pharmacological interventions for fibromyalgia.
Source Baillieres Best Pract Res Clin Rheumatol 1999 Sep;13(3): p507-23
ISSN 1521-6942
Abstract

There is little empirical evidence for the effectiveness of physical and other non-pharmacological approaches to the management of fibromyalgia. Although a number of studies have been conducted into such approaches, many of these are uncontrolled, and relatively few randomized controlled trials of appropriate size and methodological rigour have been carried out. This chapter provides an overview of the evidence available under the following headings: exercise, EMG biofeedback training, electrotherapy and acupuncture, patient education and self-management programmes, multimodal treatment approaches, and other interventions. It is hard to reach firm conclusions from the literature, owing to the variety of interventions that have been evaluated and the varying methodological quality of the studies concerned. Nonetheless, in terms of specific interventions, exercise therapy has received a moderate degree of support from the literature, and has been subjected to more randomized studies than any other intervention. In contrast, there is little or no evidence available for most types of electrotherapy. In terms of overall management strategies, a multimodal programme of management, including physical, psychological and educational components and delivered in a multidisciplinary setting, has gained some support from descriptive and experimental studies, and accords with current understanding of the aetiology and clinical features of fibromyalgia. There is a clear need for further systematic evaluation of the effectiveness of non-pharmacological treatment approaches in fibromyalgia.

12. Unique Identifier 20023802
Author Berman BM; Swyers JP
Institution University of Maryland School of Medicine, James L. Kernan Hospital, Baltimore 21207-6697, USA.
Title Complementary medicine treatments for fibromyalgia syndrome.
Source Baillieres Best Pract Res Clin Rheumatol 1999 Sep;13(3): p487-92
ISSN 1521-6942
Abstract

Fibromyalgia is a chronic-pain-related syndrome associated with high rates of complementary and alternative medicine (CAM) use. Among the many CAM therapies frequently used by fibromyalgia patients, empirical research data exist to support the use of only three: (1) mind-body, (2) acupuncture, and (3) manipulative therapies for treating fibromyalgia. The strongest data exist for the use of mind-body techniques (e.g. biofeedback, hypnosis, cognitive behavioural therapy), particularly when utilized as part of a multidisciplinary approach to treatment. The weakest data exist for manipulative techniques (e.g. chiropractic and massage). The data supporting the use of acupuncture for fibromyalgia are only moderately strong. Also, for some fibromyalgia patients, acupuncture can exacerbate symptoms, further complicating its application for this condition. Further research is needed not only in these three areas, but also for other treatments being frequently utilized by fibromyalgia patients.

13. Unique Identifier 20486105
Author O'Malley PG; Balden E; Tomkins G; Santoro J; Kroenke K; Jackson JL
Institution Division of General Internal Medicine, Walter Reed Army Medical Center Washington, DC; Uniformed Services University of the Health Sciences, Bethesda, Md; William Beaumont Army Medical Center, El Paso, Tex; Regenstrief Institute for Health Ca.
Title Treatment of fibromyalgia with antidepressants A meta-analysis [In Process Citation]
Source J Gen Intern Med 2000 Sep;15(9): p659-66
ISSN 0884-8734
Abstract

BACKGROUND: Fibromyalgia is a common, poorly understood musculoskeletal pain syndrome with limited therapeutic options.
OBJECTIVE: To systematically review the efficacy of antidepressants in the treatment of fibromyalgia and examine whether this effect was independent of depression.
DESIGN: Meta-analysis of English-language, randomized, placebo-controlled trials. Studies were obtained from searching MEDLINE, EMBASE, and PSYCLIT (1966-1999), the Cochrane Library, unpublished literature, and bibliographies. We performed independent duplicate review of each study for both inclusion and data extraction.
MAIN RESULTS: Sixteen randomized, placebo-controlled trials were identified, of which 13 were appropriate for data extraction. There were 3 classes of antidepressants evaluated: tricyclics (9 trials), selective serotonin reuptake inhibitors (3 trials), and S-adenosylmethionine (2 trials). Overall, the quality of the studies was good (mean score 5.6, scale 0-8). The odds ratio for improvement with therapy was 4.2 (95% confidence interval [95% CI], 2.6 to 6.8). The pooled risk difference for these studies was 0.25 (95% CI, 0.16 to 0.34), which calculates to 4 (95% CI, 2.9 to 6.3) individuals needing treatment for 1 patient to experience symptom improvement. When the effect on individual symptoms was combined, antidepressants improved sleep, fatigue, pain, and well-being, but not trigger points. In the 5 studies where there was adequate assessment for an effect independent of depression, only 1 study found a correlation between symptom improvement and depression scores. Outcomes were not affected by class of agent or quality score using meta-regression.
CONCLUSION: Antidepressants are efficacious in treating many of the symptoms of fibromyalgia. Patients were more than 4 times as likely to report overall improvement, and reported moderate reductions in individual symptoms, particularly pain. Whether this effect is independent of depression needs further study.

14. Unique Identifier 20023801
Author Buskila D
Institution Rheumatic Disease Unit, Soroka Medical Center, Beer Sheva, Israel.
Title Drug therapy.
Source Baillieres Best Pract Res Clin Rheumatol 1999 Sep;13(3): p479-85
ISSN 1521-6942
Abstract

Because of the lack of understanding of the basis of fibromyalgia, therapy remains empiric. This article reviews the different drug elements used in fibromyalgia, including psychotropic agents (antidepressants, sedatives and hypnotics), anti-inflammatories, analgesics and other pharmacological compounds. The strength of evidence for the therapeutic effect of each medicinal modality is presented, with the emphasis on results of randomized controlled trials. The importance of the expected effects of the current drug modalities, and whether these drugs have short- or long-term effects, are also discussed. Future directions, including testing of newer antidepressants, analgesics and non-steroidal anti-inflammatory drugs (Cox-2 selective inhibitors), as well as the need for long-term comparative trials of both drug efficacy and toxicity, are discussed.

15. Unique Identifier 94175944
Author Carette S; Bell MJ; Reynolds WJ; Haraoui B; McCain GA; Bykerk VP; Edworthy SM; Baron M; Koehler BE; Fam AG; et al
Institution Department of Medicine, Laval University, Quebec, Montreal, Canada.
Title Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial [see comments]
Source Arthritis Rheum 1994 Jan;37(1): p32-40
ISSN 0004-3591
Abstract

OBJECTIVE. To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine.
METHODS. Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo.
RESULTS. After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2-9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response.
CONCLUSION. Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.

16. Unique Identifier 96372314
Author Russell IJ
Institution Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
Title Fibromyalgia syndrome: approaches to management [published erratum appears in Bull Rheum Dis 1996 Aug; 45(5):5]
Source Bull Rheum Dis 1996 May;45(3): p1-4
ISSN 0007-5248

17. Unique Identifier 91222277
Author Russell IJ; Fletcher EM; Michalek JE; McBroom PC; Hester GG
Institution Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.
Title Treatment of primary fibrositis/fibromyalgia syndrome with ibuprofen and alprazolam. A double-blind, placebo-controlled study.
Source Arthritis Rheum 1991 May;34(5): p552-60
ISSN 0004-3591
Abstract

A multidimensional evaluation of 78 patients with primary fibrositis/fibromyalgia syndrome (PFS) revealed no significant relationship between clinical measures of physical discomfort and psychological measures. This observation provided evidence against the notion that the pain of PFS has a psychological etiology. The same patients were randomized into 4 groups for treatment with ibuprofen and/or alprazolam in a randomized, double-blind, double-dummy, placebo-controlled pilot trial. Clinical improvement in patient rating of disease severity and in the severity of tenderness upon palpation was most apparent in the subgroup of patients who were receiving both ibuprofen and alprazolam. An 8-week, open-label study in which 52 patients received both drugs further documented improvement in outcome measures. These data indicate that treatment with a combination of ibuprofen and alprazolam can be beneficial for some patients with PFS.

18. Unique Identifier 99334419
Author White KP; Speechley M; Harth M; Ostbye T
Institution Department of Medicine, University of Western Ontario, London, Canada. kevin.white@lhsc.on.ca.
Title The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario.
Source J Rheumatol 1999 Jul;26(7): p1570-6
ISSN 0315-162X
Abstract

OBJECTIVE: To estimate the point prevalence of fibromyalgia syndrome (FM) among noninstitutionalized Canadian adults; and to assess the effect of demographic variables on the odds of having FM.
METHODS: A screening questionnaire was administered via telephone to a random community sample of 3395 noninstitutionalized adults residing in London, Ontario. Individuals screening positive were invited to be examined by a rheumatologist to confirm or exclude FM using the 1990 American College of Rheumatology classification criteria.
RESULTS: One hundred confirmed cases of FM were identified, of whom 86 were women. Mean age among FM cases was 49.2 years among women, 39.3 years among men (p < 0.02). FM affects an estimated 4.9% (95% CI 4.7%, 5.1%) of adult women and 1.6% (1.3%, 1.9%) of adult men in London, for a female to male ratio of roughly 3 to one. In women, prevalence rises steadily with age from < 1% in women aged 18-30 to almost 8% in women 55-64. Thereafter, it declines. The peak prevalence in men also appears to be in middle age (2.5%; 1.1%, 5.7%). FM affects 3.3% (3.2%, 3.4%) of noninstitutionalized adults in London. Female sex, middle age, less education, lower household income, being divorced, and being disabled are associated with increased odds of having FM. CONCLUSION: FM is a common musculoskeletal disorder among Canadian adults, especially among women and persons of lower socioeconomic status.

---

Copyright © 2008 Electronic Handbook of Legal Medicine