Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [H-3]imipramine reuptake in the primary fibromyalgia syndrome

Background. Primary fibromyalgia syndrome (PFS) is a chronic disorder commo nly seen in rheumatological practice. The pathophysiological disturbances o f this syndrome, which was defined by the American College of Rheumatology in 1990, are poorly understood. This study evaluated, in 30 patients, the h ypothesis that PFS is a pain modulation disorder induced by deregulation of serotonin metabolism. Objectives. To compare platelet [H-3]imipramine binding sites and serotonin (5-HT) levels in plasma-rich platelets (PRP) of PFS patients with those of matched healthy controls and to compare the levels of biogenic amine metab olites in the cerebrospinal fluid (CSF) of PFS patients with those of match ed controls. Methods. Platelet [H-3]imipramine binding sites were defined by two criteri a, B-max for their density and K-d for their affinity. PRP 5-HT and CSF met abolites of 5-HT (5-hydroxyindoleacetic acid, 5-HIAA), norepinephrine (3-me thoxy, 4-hydroxy phenylglycol, MHPG) and dopamine (homovanillic acid, HVA) were assayed by reversed-phase high-performance liquid chromatography with coulometric detection. Results. [H-3]Imipramine platelet binding was similar (P = 0.43 for B-max a nd P = 0.30 for K-d) ill PFS patients (B-max = 901 +/- 83 fmol/mg protein, K-d = 0.682 +/- 0.046) and in matched controls (B-max = 1017 +/- 119 fmol/m g protein, K-d = 0.606 +/- 0.056). PRP 5-HT was significantly higher (P = 0 .0009) in PFS patients (955 +/- 101 ng/10(9) platelets) than in controls (6 33 +/- 50 ng/10(9) platelets). When adjusted for age, the levels of all CSF metabolites were lower in PFS patients. The CSF metabolite of norepinephri ne (MHPG) was lower (P = 0.003) in PFS patients (8.33 +/- 0.33 ng/ml) than in matched controls (9.89 +/- 0.31 ng;ml) and 5-HIAA was lower (P = 0.042) in PFS female patients (22.34 +/- 1.78 ng/ml) than in matched controls (25. 75 +/- 1.75 ng/ml). For HVA in females, the difference between PFS patients (36.32 +/- 3.20 ng/ml) and matched controls (38.32 +/- 2.90 ng/ml) approac hed statistical significance (P = 0.054). Conclusion. Changes in metabolites of CSF biogenic amines appear to be part ially correlated to age but remained diagnosis-dependent. High levels of PR P 5-HT in PFS patients were associated with low CSF 5-HIAA levels in female patients but were not accompanied by any change in serotonergic uptake as assessed by platelet [H-3]imipramine binding sites. These findings do not a llow us to confirm that serotonin metabolism is deregulated in PFS patients .