title: Cold suppresses agonist-induced activation of TRPV1.
abstract: Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.
authors.affiliation: Department of Neural and Pain Sciences, University of Maryland Dental School, Program in Neuroscience, 650 W. Baltimore Street, Baltimore, MD 21201, USA. mchung@umaryland.edu
authors.forename: M-K
authors.initials: MK
authors.lastname: Chung
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003080:Cold Temperature; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D010149:Postoperative Pain / Q000628:therapy*; D011671:Pulpitis / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors*; D014081:Tooth Extraction; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects
chemical_list: D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin