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

Rheumatology 2001; 40: 290-296

Original Papers

E. Legangneux, J. J. Mora1, O. Spreux-Varoquaux2, I. Thorin, M. Herrou3, G. Alvado4 and C. Gomeni5. Department of Psychiatry, University of Caen,

1 Department of Rheumatology, Hospital of Bayeux,

2 Department of Pharmacology, Hospital of Versailles,

3 Department of Pharmacology, University of Caen,

4 Department of Surgery, Hospital of Bayeux and

5 Biotrial, rue Jean-Louis Bertrand, Rennes, France

Background. Primary fibromyalgia syndrome (PFS) is a chronic disorder commonly seen in rheumatological practice. The pathophysiological disturbances of this syndrome, which was defined by the American College of Rheumatology in 1990, are poorly understood. This study evaluated, in 30 patients, the hypothesis that PFS is a pain modulation disorder induced by deregulation of serotonin metabolism.

Objectives. To compare platelet [3H]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 metabolites in the cerebrospinal fluid (CSF) of PFS patients with those of matched controls.

Methods. Platelet [3H]imipramine binding sites were defined by two criteria, Bmax for their density and Kd for their affinity. PRP 5-HT and CSF metabolites of 5-HT (5-hydroxyindoleacetic acid, 5-HIAA), norepinephrine (3-methoxy, 4-hydroxy phenylglycol, MHPG) and dopamine (homovanillic acid, HVA) were assayed by reversed-phase high-performance liquid chromatography with coulometric detection.

Results. [3H]Imipramine platelet binding was similar (P=0.43 for Bmax and P=0.30 for Kd) in PFS patients (Bmax=901±83 fmol/mg protein, Kd=0.682±0.046) and in matched controls (Bmax=1017±119 fmol/mg protein, Kd=0.606±0.056). PRP 5-HT was significantly higher (P=0.0009) in PFS patients (955±101 ng/109 platelets) than in controls (633±50 ng/109 platelets).

When adjusted for age, the levels of all CSF metabolites were lower in PFS patients. The CSF metabolite of norepinephrine (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) approached statistical significance (P=0.054).

Conclusion. Changes in metabolites of CSF biogenic amines appear to be partially correlated to age but remained diagnosis-dependent. High levels of PRP 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 [3H]imipramine binding sites. These findings do not allow us to confirm that serotonin metabolism is deregulated in PFS patients.

KEY WORDS: Primary fibromyalgia syndrome, Matched controls, Serotonin, Norepinephrine, Dopamine, Cerebrospinal fluid.

Correspondence to: E. Legangneux, Sanofi Synthelabo, 1 Av. Pierre Brossolette, F-91380 Chilly-Mazarin, France.

© 2001 British Society for Rheumatology

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