Project Summary
Although acute pain serves an essential protective function, many types of chronic pain including inflammatory, neuropathic, and cancer pain cause disabilities and significantly impact life quality. Nerve growth factor (NGF) and its membrane receptor TrkA are potent mediators of chronic pain. Despite their vast potential as therapeutic targets, the question of how NGF/TrkA plays a role in pain remains unanswered. In particular, how NGF differentially sensitizes pain in sensory neurons versus in the central nervous system (CNS) remains to be elucidated. To fill this gap in knowledge, we propose to develop a novel approach: to activate TrkA directly with light, in the absence of NGF. This light-inducible approach allows high spatial and temporal control of TrkA activation. We will use these new light-inducible TrkA systems to establish the consequence of TrkA activation on the excitability of sensory neurons detecting painful stimuli, on neurotransmission between these sensory neurons and CNS pain circuits, and on acute and chronic pain perception with in vivo behavioral pain tests. By bridging scientific disciplines, this project will significantly broaden our understanding of TrkA function in pain sensation, and in the longer term, of other neurological disorders influenced by TrkA and/or other neurotrophin receptors.
