(192) The Impact of Stress and Sex on Sympathetic Regulation of Dural Vessel Tone

Abstract

Migraine is a common, disruptive, and often debilitating neurological disorder that the World Health Organization classifies in the highest disability category. Migraine is up to three times more common in women than men. Attacks are commonly triggered by stress, and many migraineurs show signs of sympathetic dysregulation. While the vascular hypothesis for migraine has largely fallen from favor, there are still several lines of evidence to suggest that dysregulation of the dural vasculature may contribute to the initiation of a migraine attack. These include the evidence that migraine pain arises from dural nociceptors, that the dural vasculature is heavily innervated by both nociceptors and sympathetic post-ganglionic neurons, that vascular endothelial cells may be a source of inflammatory mediators contributing to the sensitization and activation of dural nociceptors, and that the vasculature is a primary target for CGRP, a peptide that appears to play a central role in both the initiation and maintenance of pain associated with a migraine attack. We hypothesized that stress would result in a sex-dependent loss of sympathetic control over dural vasculature. Male and female rats were randomized to one of three groups: naive, acute stress (studied right after stress) or recovery (studied 24 hrs after stress). Stress consisted of a 30-minute immobilization restraint. A bipolar electrode was placed in the superior cervical ganglion (SCG) and the skull was thinned over the middle meningeal artery. FITC-dextran was used to visualize dural blood vessels while the SCG was stimulated at differing frequencies. Vasopressin and nitroprusside were used to establish the minimum and maximum vessel diameters, respectively, per rat. Preliminary results suggest that the SCG stimulation frequency range of vessel regulation is sex-dependent and may be shifted in stressed animals. A stress-induced loss of sympathetic regulation of dural vessels could contribute to migraine initiation.