title: Polymodal Transient Receptor Potential Vanilloid Type 1 Nocisensor: Structure, Modulators, and Therapeutic Applications.
abstract: Transient receptor potential (TRP) channels belong to a superfamily of sensory-related ion channels responding to a wide variety of thermal, mechanical, or chemical stimuli. In an attempt to comprehend the piquancy and pain mechanism of the archetypal vanilloids, transient receptor potential vanilloid (TRPV) 1 was discovered. TRPV1, a well-established member of the TRP family, is implicated in a range of functions including inflammation, painful stimuli sensation, and mechanotransduction. TRPV1 channels are nonselective cation receptors that are gated by a broad array of noxious ligands. Such polymodal-sensor aspect makes the TRPV1 channel extremely versatile and important for its role in sensing burning pain. Besides ligands, TRPV1 signaling can also be modulated by lipids, secondary messengers, protein kinases, cytoskeleton, and several other proteins. Due to its central role in hyperalgesia transduction and inflammatory processes, it is considered as the primary pharmacological pain target. Moreover, understanding the structural and functional intricacies of the channel is indispensable for the therapeutic intervention of TRPV1 in pain and other pathological disorders. In this chapter, we seek to give a mechanistic outlook on the TRPV1 channel. Specifically, we will explore the TRPV1 structure, activation, modulation, ligands, and its therapeutic targeting. However, the major objective of this review is to highlight the fact that TRPV1 channel can be treated as an effective therapeutic target for treating several pain- and nonpain-related physiological and pathological states.
authors.affiliation: National Leading Research Laboratory of Molecular Modeling & Drug Design (NLRL), College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Minghua
authors.initials: M
authors.lastname: Cui
authors.affiliation: National Leading Research Laboratory of Molecular Modeling & Drug Design (NLRL), College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Gosu
authors.affiliation: National Leading Research Laboratory of Molecular Modeling & Drug Design (NLRL), College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Shaherin
authors.initials: S
authors.lastname: Basith
authors.affiliation: National Leading Research Laboratory of Molecular Modeling & Drug Design (NLRL), College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Sunhye
authors.initials: S
authors.lastname: Hong
authors.affiliation: National Leading Research Laboratory of Molecular Modeling & Drug Design (NLRL), College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea. Electronic address: sunchoi@ewha.ac.kr.
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics; D008024:Ligands; D058990:Molecular Targeted Therapy; D009154:Mutation; D010146:Pain / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*
chemical_list: D000700:Analgesics; D008024:Ligands; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human
keywords: Agonist; Antagonist; Capsaicin; Hyperalgesia; Ion channel; Nociceptor; Pain; TRPV1; Vanilloid