Pathophysiological role of TRPC3 in the development of neuropathic pain

Abstract

Neuropathic pain is a pathological pain condition that often caused by peripheral nerve injury. Accumulating evidence suggests that central nervous system (CNS) inflammation, which is mediated by the interaction between neurons and glial cells/peripheral immune cells, plays a pivotal role in the development of neuropathic pain. Transient receptor potential canonical (TRPC3), a Ca²⁺-permeable nonselective cation channel, is widely expressed in the CNS, primary sensory neurons, and peripheral immune cells. In this study, we investigated the involvement of TRPC3 in neuropathic pain after peripheral nerve injury. Naïve TRPC3-knockout (KO) mice displayed normal mechanical/thermal sensitivities, but TRPC3-deficiency impaired mechanical/thermal hyperalgesia in a mouse model of partial sciatic nerve ligation (pSNL). Using bone marrow chimeric mice, we also showed that TRPC3 in CNS or primary sensory neurons, but not in peripheral immune cells, is required for the development of pSNL-induced mechanical hyperalgesia. Moreover, intrathecal administration of GSK1702934A, a TRPC3 agonist, induced acute mechanical hyperalgesia. Overall, TRPC3 plays an important role in the development of neuropathic pain after peripheral nerve injury.