Inhibition of nociceptive dural input to the trigeminocervical complex through oxytocinergic transmission

Migraine is a complex brain disorder that involves abnormal activation of the trigeminocervical complex (TCC). Since an increase of oxytocin concentration has been found in cerebrospinal fluid in migrainous patients and intranasal oxytocin seems to relieve migrainous pain, some studies suggest that the hypothalamic neuropeptide oxytocin may play a role in migraine pathophysiology. However, it remains unknown whether oxytocin can interact with the trigeminovascular system at TCC level. The present study was designed to test the above hypothesis in a well-established electrophysiological model of migraine. Using anesthetized rats, we evaluated the effect of oxytocin on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We found that spinal oxytocin significantly reduced TCC neuronal firing evoked by meningeal electrical stimulation. Furthermore, pretreatment with L-368,899 (a selective oxytocin receptor antagonist, OTR) abolished the oxytocin-induced inhibition of trigeminovascular neuronal responses. This study provides the first direct evidence that oxytocin, probably by OTR activation at TCC level inhibited dural nociceptive-evoked action potential in this complex. Thus, targeting OTR at TCC could represent a new avenue to treat migraine.