Optogenetic Modulation of the Visceromotor Response to Reveal Visceral Pain Mechanisms

Visceral pain is a debilitating condition that is common yet lacks effective treatments. In the case of gastrointestinal disorders (e.g., inflammatory bowel disease and irritable bowel syndrome), pain is thought to be conveyed by primary afferent fibers innervating the colon. These fibers differ in their response properties, anatomical structures, and molecular phenotypes; thus, it is unclear which afferents initiate and maintain changes in visceral sensitivity. Additionally, evidence shows that nonneuronal cell types in the colon (e.g., epithelial cells) can initiate colon afferent activity, indicating that they are an integral part of sensory signaling. Measurement of the visceromotor response (VMR) is an established, reliable method to assess visceral sensitivity to mechanical stimuli. In order to determine the relative contribution of specific cell types to the VMR, our lab has developed techniques utilizing optogenetic mouse models. These techniques will enable researchers to define how subtypes of afferent neurons and nonneuronal cell populations contribute to visceral pain in both normal and pathological conditions. This chapter details how optogenetics can be integrated into VMR analysis, for assessment of colon sensitivity in vivo. These methods can be adapted to other visceral organs and also used in disease models.