Journal: Psychoneuroendocrinology, 2006, September 6; [E-publication ahead of print] Authors and Affiliation: Bonifazi M, Lisa Suman A, Cambiaggi C, Felici A, Grasso G, Lodi L, Mencarelli M, Muscettola M, Carli G; Dipartimento di Fisiologia, Via Aldo Moro, Universita degli Studi di Siena, I-53100 Siena, Italy. PMID: 16962248 The aim of the present study was to investigate the effects of a 3-week residential multidisciplinary non-pharmacological treatment program (including individually prescribed aerobic exercise and cognitive-behavioral therapy) on fibromyalgia symptoms and hypothalamic-pituitary-adrenal (HPA) axis function. Salivary and venous blood samples were collected from 12 female patients with Fibromyalgia (age: 25-58) the day before and the day after the treatment period: saliva, eight times (every two hours from 0800 to 2200h); venous blood, at 0800h. Peripheral blood mononuclear cells (PBMC) were separated and analyzed for glucocorticoid receptor-alpha (GR-alpha) mRNA expression by semi-quantitative RT-PCR, while the salivary cortisol concentration was determined by RIA. At the same time, pain and aerobic capacity were evaluated. Aerobic capacity improved at the end of the treatment program. The slope of the regression of salivary cortisol values on sampling time was steeper in all patients after treatment, indicating that the cortisol decline was more rapid. Concomitantly, the area under the cortisol curve '”with respect to increase” (AUC(i)) was higher and there was a significant increase in GR-alpha mRNA expression in PBMC. The number of positive tender points, present pain, pain area and CES-D score were significantly reduced after the treatment, while the pressure pain threshold increased at most of the tender points. Our findings suggest that one of the active mechanisms underlying the effects of our treatment is an improvement of HPA axis function, consisting in increased resiliency and sensitivity of the stress system probably related to stimulation of GR-alpha synthesis by the components of the treatment.