Sexual Dimorphism in Mouse Models of Visceral Pain

Abstract

Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are chronic gastrointestinal disorders that affect millions of people around the world. These patients manifest sexual dimorphism in the clinical manifestation and pathophysiology of disease, including differences in visceral pain perception. However, while biological sex has been increasingly considered in pain studies, sex differences in visceral pain in pathological states have been largely understudied in preclinical research. In this study, we evaluated potential sex differences in visceral pain using mouse models of acute and persistent colon inflammation. To this aim, we studied spontaneous visceral nociceptive responses using the mouse model of intracolonic capsaicin, measured referred abdominal hypersensitivity employing the von Frey test, and analyzed disease progression and bowel pathology by using the mouse model of DSS-induced colitis. Our results demonstrate sex differences in visceral pain-related behaviors and clinical progression of disease in the context of acute and persistent colon inflammation. We show that females exhibit higher visceral pain-related behaviors and referred abdominal hypersensitivity than males in the context of acute but not persistent colon inflammation. In contrast, following persistent colon inflammation, we observed no measurable sex difference in visceral pain responses, referred abdominal hypersensitivity and colitis-induced colon pathology but males exhibited a worst clinical progression of disease than females. Interestingly, the manifestation of visceral pain-related responses was sex dependent in the context of both acute and persistent colon inflammation, with increases in licking of the abdomen only observed in females and increases in abdominal contractions only seen in males. Altogether, our findings stress the need of incorporating both sexes in future visceral pain studies as we strive to have a better understanding of the mechanisms that drive pathological pain states and develop improved diagnostics and therapeutic options for patients. Grant support from National Center for Complementary and Integrative Health Intramural Research Program.