Brainmap: Brain stem mechanisms behind analgesic effects of nasal oxytocin

David C. Yeomans, PhD
Professor in the Department of Anesthesia at Stanford Medical School. 
Director of Pain Research, Stanford
Director, Medical Neuroscientist Program at Stanford
 
Chronic and high frequency migraine patients suffer with 15 or more or 8-14 moderate to severe headache days/month respectively, and are highly debilitated by these conditions. Treatment choices for these conditions are currently inadequate. For this presentation, we will show that trigeminal neurons, which are critical components in mechanisms underlying these conditions, possess oxytocin receptors the expression of which is highly dependent on inflammatory state.  Inflammation also enhances release of the pain neurotransmitter/neuromodulator calcitonin gene related peptide (CGRP) in vitro, from dural afferent nerve endings, which can be attenuated by exposure to oxytocin.  In addition, nasally-applied application of radiolabelled oxytocin in rats concentrates in the trigeminal system, suggesting direct access to trigeminal receptors.  Though this access, nasal application of oxytocin attenuates responses of brainstem neurons to painful stimulation and produces profound analgesia in craniofacial behavioral assays in rats.  These findings have led to Phase II clinical trials of a formulation of nasal oxytocin in chronic and high frequency episodic migraine.  The results of these studies demonstrate both a pain-reducing effect as well as a robust and sustained decrease in the frequency of migraine attacks and secondary migraines symptoms including nausea and vomiting, photophobia, and phonophobia.