New Dimensions in Fibromyalgia

Investigative Pathways of Diagnosis (Part I)

I. Jon Russell, M.D., Ph.D.

OBJECTIVES: Digital pressure at 18 anatomically defined tender points (TPs) is one component required for the diagnosis of fibromyalgia syndrome (FMS). There is a need for highly reliable measures to use as clinical gauges against which new biological measures can be statistically compared. The present analysis assessed the reliability of 2 tenderness severity measures: tender point idex (TPI) by digital palpation, average pain threshold (APT) by algometry and their relationships to other clinical measures.

METHODS: FMS patients free of analgesic and sedative hypnotic medications for two weeks were enrolled from a University-based rheumatology practice. At 2-week intervals, self-report measures included Visual Analog Scales (PAIN, SLEEP, HEADACHE, STIFFNESS) and validated questionnaires (HAQ-disability, HASSLES-anxiety, CES-Depression). TP measures were obtained by a single examiner.

RESULTS: Enrolled subjects (N=110) exhibited a quality of life altered by somatic and affective symptoms. Measurement of TP tenderness in 90 “medication-free” FMS patients disclosed a range of TPI and APT values. Analysis of test-retest values showed a reliability for APT (R=0.85) comparable with CESD, HASSLES, HAQ; and better than TPI (R=0.77). TPI and APT both correlated with PAIN, STIFFNESS, HAQ, while only TPI correlated with CESD. The initial correlation between TPI and APT was high (R=0.63) and increased (R=0.73) with serial assessments. The ratio TPI:APT was dependent on somatic (PAIN, SLEEP, HAQ) but not on affective (HASSLES, CESD) measures.

CONCLUSIONS: The wide range of TPI or APT values could be used to stratify patients into clinical subgroups on the basis of tenderness severity. Both TPI and APT are highly reliable measures of tenderness severity to deep pressure at TPs in FMS but they may be most readily applicable to different clinical settings. TPI relates more to psychological measures than does APT. The use of multiple measures to assess FMS enhances understanding of the disorder.

Investigative Pathways of Diagnosis (Part 2)

OBJECTIVES: Two neurochemical models may be mechanistically relevant to central nervous system (CNS)-mediated pain in fibromyalgia syndrome (FMS). They are serotonin (5HT) deficiency and excesses of substance P (SP). New findings in these interdependent models support their validity in FMS.

METHODS: FMS patients and controls, medication-free for weeks, were enrolled and clinically evaluated in a University-based rheumatology practice. Cerebrospinal fluid (CSF) and peripheral platelets (PLT) were collected. CSF was examined by HPLC for metabolites of the trptophan (TRP)/5HT/kynurenine (KYN) pathways. Platelets were examined for 5HT levels, 5HT uptake, and in vitro aggregation before and after 2-weeks of 5HT uptake inhibitor therapy. SP was measured once in CSF from FMS and controls plus a second time in CSF from 28 FMS an average of 12 months later.

RESULTS: Platelet 5HT levels were low in a subgroup of FMS and correlated with symptoms. Platelet uptake of 5HT was inhibited in vitro by oral use of 5HT uptake inhibitors (SRI). Platelet aggregation was decreased in untreated FMS but was corrected by SRI. In FMS CSF, low levels of TRP, 5HTRP, and 5HIAA contrasted with high KYN. CSF SP was elevated in most, but not all FMS. It was highest in primary FMS, lower in secondary FMS, and nearly normal in non-FMS disease controls. The presence of diabetes mellitus did not influence CSF SP in FMS. Acute manipulation of lower extremity tender points had little effect on CSF SP. Repeat testing of FMS CSF SP showed an overall increase in CSF SP with time which correlated with pain/tenderness (TPI,TPA) but not with depression.

CONCLUSIONS: FMS subgroups exhibit abnormalities in both central and peripheral 5HT which correlate with FMS symptoms and suggest a clinically relevant, widespread defect in 5HT production and/or availability in FMS. FMS subgroups exhibit central abnormalities in SP levels which could be due to low 5HT and appear to change in concert with painful FMS symptoms. Therefore, subgroup of clinically similar FMS may be distinguished biologically by physiologically relevant laboratory abnormalities.

Presented at the National Fibromyalgia Research Association's New Dimensions in Fibromyalgia Symposium, September 14-15, 1997, in Portland, Oregon.


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