The underlying cause of recurrent pain in the bladder, pelvis or urogenital floor that is a defining feature of pelvic pain disorders is not known. In other aspects of the nervous system, serotonin (5-HT) has been implicated in pain sensation and 5-HT increases in peripheral tissues with inflammation or thermal injury. Serotonin receptors (5-HTRs) can alter nociception by potentiating activity of the transient receptor potential V1 channel (Trpv1). Despite their known roles in nociception and effects on nociceptive channels like Trpv1 in other areas of the nervous system, there is a big knowledge gap about 5-HTRs in innervation of the urogenital system.
We have documented expression of 5-HTRs in populations of bladder-projecting neurons that provides the basis for the studies in this project. The goals of our nGUDMAP effort are to gain a broader appreciation of the potential roles for 5-HTR signaling in sensory neurons that innervate pelvic organs and define relationships between 5-HTRs and other known nociceptive molecules. We are pursuing our studies in late fetal and postnatal mice during stages when mechanisms that control micturition are maturing. In Aim 1 we are using immunohistochemical approaches to co-localize 5-HTRs with markers of specific nociceptive subtypes. In Aim 2 we are using transgenic lines expressing fluorescent reporters to capture and derive RNASeq transcriptome profiles from bladder-projecting sensory neurons in dorsal root ganglia that express 5-HTRs. In Aim 3 to provide a means to interrogate the relationship between 5-HTRs and Trpv1, we are generating a mouse line that expresses multiple fluorophores for live cell imaging of calcium flux among Trpv1+ neuronal populations. The results gained will define the distribution of 5-HTRs that may participate in peripheral sensitization and should direct future hypothesis-driven studies on the role of 5-HTRs in development and disease of lower urinary tract innervation.
Grant number: 1U01DK101038