408) Cytokine dependence of the analgesic effect of nasal oxytocin in chronic migraineurs

This study examined the importance of cytokine-drivenoxytocin receptor upregulation in determining the efficacy of nasal oxytocin (OT) in chronic migraine patients. Oxytocin receptor (OT-R) expression is known to be driven by cytokines, and particularly by IL6, for which there are early response elements on the OT-R gene promoter. As OT-R are on trigeminal nerve neurons, their level should thus be enhanced by IL-6 as should the analgesic effect of OT for trigeminally mediated pain wherein there is an inflammatory component, including chronic migraine. This study included a single-dose, placebocontrolled, double-blind, parallel study of the effects of 32 U of nasally-applied oxytocin in patients with chronic migraine. The primary inclusion criteria included an incidence of migraine-type headache of at least 15 days/month and the presence of a headache for at least 10 hours prior to dosing (to ensure OT-R upregulation) and patients were washed out of other medications for at least 4 hours. Patients were asked to rate their pain on a standard 4-point categorical scale (severe, moderate, mild, or none) just prior to and at 0.5, 1, 2, 4, and 24 hours after dosing; nausea, photophobia, and phonophobia were also recorded. The results of this study demonstrated that, nasal OTreduced pain by 2 categories in 42% of patients at 2 hours and 55% at 4 hrs.; compared to 11% and 28% for placebo. Patients that had taken a NSAID, which blocks IL-6 production, within 24 hours prior to dosing showed a strong decrease in effect. Nausea, photophobia and phonophobiawere also decreased compared to placebo. These results suggest that nasal oxytocin may be a viable alternative for the treatment of chronic migraine headache.