TRPV1 Signaling: Mechanistic Understanding and Therapeutic Potential

Rong      Xia; Tarek      A. Samad; Joan      Btesh; Lin-Hua      Jiang; Ibrahim      Kays; Louise      Stjernborg; Niek      Dekker

doi:10.2174/156802611796904843

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel gated by noxious heat, vanilloids and extracellular protons. TRPV1 acts as an important signal integrator in sensory nociceptors under physiological and pathological conditions including inflammation and neuropathy. Because of its integrative signaling properties in response to inflammatory stimuli, TRPV1 agonists and antagonists are predicted to inhibit the sensation of ongoing or burning pain that is reported by patients suffering from chronic pain, therefore offering an unprecedented advantage in selectively inhibiting painful signaling from where it is initiated. In this article, we summarize recent advances in the understanding of the role of TRPV1 in pain signaling, including an overview of clinical pharmacological trials using TRPV1 agonists and antagonists. Finally, we also present an update on the mechanistic understanding and controlling of hyperthermia caused by TRPV1 antagonists, and provide perspectives for future studies.

Keywords: TRP, Ion channel, therapy, thermoregulation, hyperthemia, agonist, antagonist, TRPV1 Signaling, TRPV1, noxious heat, vanilloids and extracellular protons, sensory nociceptors, inflammation, neuropathy, TRPV1 agonists and antagonists