GLUCOCORTICOID RECEPTORS, FIBROMYALGIA AND LOW-BACK-PAIN

Recently, fibromyalgia (FMS) was shown to be a disorder associated wit h an altered functioning of the stress response system. FMS patients d isplay a hyperreactive pituitary adrenocorticotropic hormone (ACTH) re lease in response to corticotropin-releasing hormone (CRH) and to insu lin-induced hypoglycemia. We suggested that negative feedback of corti sol could be deranged. Therefore we investigated the properties and fu nction of the glucocorticoid receptors (GR) in FMS patients and compar ed the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS pat ients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sede ntary control persons were recruited for the study. Urinary free corti sol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concent rations when compared to controls. However, plasma free cortisol conce ntrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation const ant (K-d) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/ l) subjects was significantly higher than that of the controls (10.9 /- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05 ) than in the control or LBP group. The ED50 (the cortisol concentrati on giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a m ild hypocortisolemia, increased cortisol feedback resistance in combin ation probably with a reduced CRH synthesis or release in the hypothal amus. The role of the GR and mineralocorticoid receptor (MR) in the CR H regulation in the FMS patients remains to be solved. (C) 1997 Elsevi er Science Ltd. All rights reserved.