Sex Difference in the Inflammatory Mediator-induced 1 Sensitization of Dural Afferents

24 Approximately 20% of the adult population suffers from migraine. This debilitating 25 pain disorder is 3 times more prevalent in women than in men. To begin to evaluate 26 the underlying mechanisms that may contribute to this sex difference, we tested the 27 hypothesis that there is a sex difference in the inflammatory mediator (IM)-induced 28 sensitization of dural afferents. Acutely dissociated retrogradely labeled dural 29 afferents from adult Sprague Dawley rats were examined using whole cell patch30 clamp recordings. Baseline passive and active electrophysiological properties of 31 dural afferents from both sexes were comparable. However, while the IM-induced 32 increase in the excitability of dural afferents from male and female rats was also 33 comparable, the proportion of dural afferents from female rats sensitized by IM 34 (~100%) was significantly greater than that of dural afferents from male rats 35 (~50%). This appeared to be due to differences down-stream of IM receptors as 36 TTX-R sodium current was increased by IM in a majority of male dural afferents 37 (13/14). These data indicate that there are both quantitative and qualitative 38 differences in the IM-induced sensitization of dural afferents that may contribute to 39 the sex difference in the manifestation of migraine. 40 41