A reduced functionality of Gi proteins as a possible cause of fibromyalgia

Objective. The etiopathogenesis of fibromyalgia (FM), a syndrome characteri zed by widespread pain and hyperalgesia, is still unknown. Since the involv ement of Gi proteins in the modulation of pain perception has been widely e stablished, the aim of the present study was to determine whether an altere d functionality of the Gi proteins occurred in patients with FM. Methods. Patients with FM and other painful diseases such as neuropathic pa in, rheumatoid arthritis (RA), and osteoarthritis, used as reference painfu l pathologies, were included in the study. The functionality, evaluated as capability to inhibit forskolin-stimulated adenylyl cyclase activity, and t he level of expression of Gi proteins were investigated in peripheral blood lymphocytes. Results. Patients with FM showed a hypofunctionality of the Gi protein syst em. In contrast, unaltered Gi protein functionality was observed in patient s with neuropathic pain, RA, and osteoarthritis. Patients with FM also show ed basal cAMP levels higher than controls. The reduced activity of Gi prote ins seems to be unrelated to a reduction of protein levels since only a sli ght reduction (about 20-30%) of the Gi(3 alpha) subunit was observed. Conclusions: Gi protein hypofunctionality is the first biochemical alterati on observed in FM that could be involved in the pathogenesis of this syndro me. In the complete absence of laboratory diagnostic tests, the determinati on of an increase in cAMP basal levels in lymphocytes, together with the as sessment of a Gi protein hypofunctionality after adenylyl cyclase stimulati on, may lead to the biochemical identification of patients with FM.