(372) Sex differences in peripheral serotonergic pain processing in male and female rats

Abstract

Many persistent pain conditions occur predominantly in women making pain a major women’s health issue. As the majority of pain research has been conducted in males, the mechanisms underlying pain in women are unclear. One theory for the prevalence of pain disorders in females is steroid hormone modulation of pain mechanisms. The monoamine neurotransmitter serotonin (5HT) has been highly implicated in various pain conditions that are more prevalent in women. Our recent studies found that peripheral 5HT (1) evokes pain via a subpopulation of trigeminal nociceptors expressing the transient receptor potential V1 channel (TRPV1) and (2) potentiates capsaicin-evoked proinflammatory peptide release from human tooth pulp during the luteal phase of the menstrual cycle. No studies have yet examined the effect of hormone modulation on 5HT-evoked pain in females. We hypothesized that peripheral 5HT evokes greater pain behaviors in female rodents during stages of the estrous cycle when steroid hormones are fluctuating. Female Sprague-Dawley rats (250-350 g) from each stage of the estrous cycle, ovariectomized rats, and intact males were acclimated to the testing apparatuses. Rats received a hindpaw injection of 5HT (2 μg / 100uL; ipl) or saline (n = 6 / group) and thermal hyperalgesia and mechanical allodynia were measured at 10, 20 and 30 minutes. Here we report that female rats in proestrus and estrus exhibited significantly greater and longer-lasting pain behaviors following 5HT injection compared to males, diestrus females, and ovariectomized females, while there was no significant change in edema. These data implicate a modulatory role of hormones on 5HT-evoked pain processing, which may underlie the greater prevalence of pain disorders in women. Our current studies are elucidating the potential enhancing effect of 17-β-estradiol treatment on serotonergic potentiation of the TRPV1 population of sensory neurons in culture. Supported by a Research Enhancement Grant from Texas Woman’s University.