Involvement of corticotrophin-releasing factor and orexin-A in chronic migraine and medication-overuse headache: findings from cerebrospinal fluid.
The study set out to investigate the role of corticotrophin-releasing factor (CRF) and orexin-A in chronic migraine (CM) and medication-overuse headache (MOH). Twenty-seven patients affected by CM and 30 with MOH were enrolled. Control CSF specimens were obtained from 20 age-matched subjects who underwent lumbar puncture for diagnostic purposes, and in all of them CSF and blood tests excluded central nervous system or systemic diseases. Orexin-A and CRF were determined by radioimmunoassay methods. Significantly higher levels of orexin-A and CRF were found in the CSF of MOH and to a lesser extent in patients with CM compared with control subjects (orexin-A: P < 0.001 and P < 0.02; CRF: P < 0.002 and P < 0.0003). A significant positive correlation was also found between CSF orexin-A values and those of CRF (R = 0.71; P < 0.0008), monthly drug intake group (R = 0.39; P < 0.03) and scores of a self-completion 10-item instrument to measure dependence upon a variety of substances, the Leeds Dependence Questionnaire (LDQ) in the MOH group (R = 0.68; P < 0.0003). The significantly higher orexin-A levels found in CM and MOH can be interpreted as a compensatory response to chronic head pain or, alternatively, as an expression of hypothalamic response to stress due to chronic pain. A potential role for orexin-A in driving drug seeking in MOH patients through activation of stress pathways in the brain can also be hypothesized.
Sarchielli
P
P
Neurologic Clinic, University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it
Rainero
I
I
Coppola
F
F
Rossi
C
C
Mancini
Ml
M
Pinessi
L
L
Calabresi
P
P
D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D003346:Corticotropin-Releasing Hormone / Q000134:cerebrospinal fluid*; D004359:Drug Therapy, Combination; D005260:Female; D020773:Headache Disorders / Q000175:diagnosis / Q000503:physiopathology*; D051271:Headache Disorders, Secondary / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000175:diagnosis / Q000503:physiopathology*; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D011863:Radioimmunoassay; D012016:Reference Values; D013129:Spinal Puncture; D013312:Stress, Physiological / Q000503:physiopathology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D003346:Corticotropin-Releasing Hormone