Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation.
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Biomedical subjects
Publications and source records attributed to M B Yunus.
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To test the hypothesis that plasma tryptophan and/or its transport ratio is decreased in primary fibromyalgia (PF), we measured plasma tryptophan and its transport ratio in 29 patients with PF and 30 healthy controls without significant pain, in a blinded manner. Twenty-one other amino acids were also similarly analyzed among these study subjects. Transport ratio of tryptophan was found to be significantly (p less than 0.01) decreased in PF compared with the control group (0.09 +/- 0.02 vs 0.10 +/- 0.02). Plasma tryptophan level was lower in PF (45 +/- 10 nmol/ml) than in healthy controls (51 +/- 15 nmol/ml), showing a trend towards significance (p less than 0.09). Additionally, plasma histidine and serine levels were found to be significantly (p less than 0.01) lower in patients with PF than in controls. Our results suggest that a decreased brain serotonin level, as possibly reflected by a decreased transport ratio of plasma tryptophan, may play a pathophysiologic role in PF.
Plasma and urinary catecholamines were measured in a blinded manner among 30 patients with primary fibromyalgia (PF) and 30 healthy controls without significant pain to determine possible elevations of catecholamines in PF, as well as their correlations with psychological and clinical variables in this syndrome. Results showed no significant differences between fibromyalgia and control groups in any of the catecholamines measured, nor was there a correlation between catecholamine levels and any of the clinical features or psychologic measures.
Clinical features and psychological status determined by the Minnesota Multiphasic Personality Inventory (MMPI) in 103 patients with primary fibromyalgia syndrome (PFS) were analyzed by univariate and multivariate techniques to determine if clinical features were related to psychological status or were intrinsic to PFS per se. The central features of PFS, e.g., number of pain sites, number of tender points, fatigue, and poor sleep, were independent of psychological status. However, discriminant analysis identified 4 variables--patient-reported depression, anxiety, stress, and pain severity--which together predicted 3 MMPI subgroups with an accuracy of 55% (P less than 0.001); the only musculoskeletal feature--pain severity--alone provided an accuracy of only 34% (P greater than 0.05). These data suggest a new concept, that the central features of fibromyalgia are independent of the psychological status and are more likely related to the PFS itself. However, pain severity may be influenced by psychological factors.
OBJECTIVE: The major purpose of this study was to compare the frequency of the occurrence of DSM-III diagnoses in patients with primary fibromyalgia syndrome, patients with rheumatoid arthritis, and subjects without pain. METHOD: Thirty-five patients with primary fibromyalgia, 33 patients with rheumatoid arthritis, and 31 nonpatients without pain were blindly assessed for psychiatric diagnoses with the Psychiatric Diagnostic Interview. RESULTS: Data from this interview revealed no group differences in terms of lifetime history of any psychiatric disorders, including major depression, somatization disorder, or anxiety-based disorders. Analysis of the auxiliary symptoms of depression on the Psychiatric Diagnostic Interview revealed that the patients with fibromyalgia did not report a higher frequency of vegetative signs of depression. However, analysis of the somatization scale revealed an interaction between medical and psychiatric diagnoses: patients with primary fibromyalgia syndrome and a psychiatric history endorsed significantly more somatic symptoms than did patients with rheumatoid arthritis or subjects without pain, and fibromyalgia patients without a psychiatric history were no more likely to endorse somatic symptoms than were arthritis patients or subjects without pain. CONCLUSIONS: The Psychiatric Diagnostic Interview data failed to discriminate in any major way between primary fibromyalgia syndrome (a disorder with no known organic etiology) and rheumatoid arthritis (a disorder with a known organic etiology). Therefore, these data do not support a psychopathology model as a primary explanation of the symptoms of primary fibromyalgia syndrome.
To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.
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