Bradykinin-mediated Sensitization and Receptor Expression in Human Sensory Neurons

Abstract

Differences in nociceptor physiology between humans and rodents is a major roadblock in the successful translation of preclinical analgesic targets to clinical therapy. Both acute and chronic inflammation by mediators like bradykinin (BK) has been implicated in the pathogenesis of pain. However, to date, few studies have examined how BK modulates the physiology of human sensory neurons. Furthermore, the expression pattern of BK receptor subtypes in human dorsal root ganglion (hDRG) remains largely unknown. In the present study, we perform patch clamp electrophysiology experiments to examine the effects of acute and prolonged exposure to BK on the excitability of small-diameter human sensory neurons, using primary hDRG tissue from organ donors as a translational platform. Additionally, using in situ hybridization, we characterize the distribution pattern of B1 and B2 bradykinin receptors among hDRG subpopulations based on size and molecular markers. The results of the study may aid the evaluation of bradykinin signaling as a target for clinical analgesic development. Grant support from American Heart Association – 828671.