A reduced functionality of Gi proteins as a possible cause of fibromyalgia.
OBJECTIVE
The etiopathogenesis of fibromyalgia (FM), a syndrome characterized by widespread pain and hyperalgesia, is still unknown. Since the involvement of Gi proteins in the modulation of pain perception has been widely established, the aim of the present study was to determine whether an altered functionality of the Gi proteins occurred in patients with FM.


METHODS
Patients with FM and other painful diseases such as neuropathic pain, rheumatoid arthritis (RA), and osteoarthritis, used as reference painful pathologies, were included in the study. The functionality, evaluated as capability to inhibit forskolin-stimulated adenylyl cyclase activity, and the level of expression of Gi proteins were investigated in peripheral blood lymphocytes.


RESULTS
Patients with FM showed a hypofunctionality of the Gi protein system. In contrast, unaltered Gi protein functionality was observed in patients with neuropathic pain, RA, and osteoarthritis. Patients with FM also showed basal cAMP levels higher than controls. The reduced activity of Gi proteins seems to be unrelated to a reduction of protein levels since only a slight reduction (about 20-30%) of the Gi3alpha subunit was observed.


CONCLUSIONS
Gi protein hypofunctionality is the first biochemical alteration observed in FM that could be involved in the pathogenesis of this syndrome. In the complete absence of laboratory diagnostic tests, the determination of an increase in cAMP basal levels in lymphocytes, together with the assessment of a Gi protein hypofunctionality after adenylyl cyclase stimulation, may lead to the biochemical identification of patients with FM.
Galeotti
N
N
Department of Pharmacology, Headache Center, University of Florence, Italy.
Ghelardini
C
C
Zoppi
M
M
Bene
E D
ED
Raimondi
L
L
Beneforti
E
E
Bartolini
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005356:Fibromyalgia / Q000209:etiology* / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases