Neuroendocrine and hormonal perturbations and relations to the serotonergic system in fibromyalgia patients

The symptomatology of the fibromyalgia syndrome (FMS) often resembles an al teration in central nervous set points at least in three systems. The patie ns suffer under chronic pain in the region of the locomotor system, presuma bly reflecting a disturbed central processing of pain. Anxiety and depressi on often characterizes the clinical picture. Almost all of the hormonal fee dback mechanisms controlled by the hypothalamus are altered. Characteristic for FMS patients are the elevated basal values of ACTH, follicle-stimulati ng hormone (FSH), and cortisol as well as lowered basal values of insulin-l ike growth factor 1 (IGF-1, somatomedin C), free triiodothyronine (FT3), an d oestrogen. In FMS patients, the systemic administration of the relevant r eleasing hormones of corticotropin-releasing hormone (CRH), growth hormone- releasing hormone (GHRH), thyreotropin-releasing hormone (TRH), and luteini zing hormone-releasing hormone (LHRH) leads to increased secretion of ACTH and prolactin, whereas the degree to which TSH can be stimulated is reduced . The stimulation of the hypophysis with LHRH in female FMS patients during their follicular phase results in a significantly reduced LH response. All in all, the typical alterations in set points of hormonal regulation that are typical for FMS patients can be explained as a primary stress activatio n of hypothalamic CRH neurons caused by the chronic pain. In addition to th e stimulation of pituitary ACTH secretion, CRH activates somatostatin on th e hypothalamic level, which in turn inhibits the release of GH and TSH on t he hypophyseal level. The lowered oestrogen levels could be accounted for b oth via an inhibitory effect of the CRH on the hypothalamic release of LHRH or via a direct CRH-mediated inhibition of the FSH-stimulated oestrogen pr oduction in the ovary. Serotonin (5HT), precursors like tryptophan (5HTP), drugs which release 5HT or act directly on 5HT receptors stimulate HPA axis, indicating a stimulat ory serotonergic influence on HPA axis function. Therefore activation of th e HPA axis may reflect an elevated serotonergic tonus in the central nervou s system of FMS patients.