TRPC3/6 Channels Mediate Mechanical Pain Hypersensitivity via Enhancement of Nociceptor Excitability and of Spinal Synaptic Transmission.

ABSTRACT: Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic

SUBMITTER: Sun ZC 

PROVIDER: S-EPMC11600220 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature