Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Disrupting sensitization of transient receptor potential vanilloid subtype 1 inhibits inflammatory hyperalgesia.

Authors: Michael J M Fischer, Joan Btesh, Peter A McNaughton

Journal, date & volume: J. Neurosci., 2013 Apr 24 , 33, 7407-14

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23616546

Abstract
Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel that plays a key role in enhanced pain sensation after inflammation, but directly blocking TRPV1 causes hyperthermia and decreased sensitivity to painful levels of heat in animals and humans. Here we explore an alternative analgesic strategy in which the modulation of TRPV1 is inhibited by antagonizing the interaction between TRPV1 and A kinase anchoring protein 79 (AKAP79), a scaffolding protein essential for positioning serine-threonine kinases adjacent to target phosphorylation sites. We first defined key residues in the domain in TRPV1 that interacts with AKAP79, and we then used this information to construct short peptides capable of preventing TRPV1-AKAP79 interaction. An effective peptide, when coupled to a TAT sequence conferring cell permeability, was found to be analgesic in three mouse models of inflammatory hyperalgesia. These results demonstrate the potential value of interfering with the interaction between TRPV1 and AKAP79 as a novel analgesic strategy.