J Dent Res. 2011 Sep;90(9):1098-102. doi: 10.1177/0022034511412074. Epub 2011 Jun 10.

Cold suppresses agonist-induced activation of TRPV1.

Source

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

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.

PMID:: 21666106; [PubMed – indexed for MEDLINE]
PMCID:: PMC3169882

Free PMC Article

Journal club 2012-12-07

By onlynice20

TRPA1 underlies a sensing mechanism for O2

nchembio.640 , nchembio.640-S1

nobuaki takahashi1–3, tomoyuki Kuwaki4, shigeki Kiyonaka1,2,5, tomohiro numata1,2, daisuke Kozai1,2, Yusuke Mizuno1,2, shinichiro Yamamoto1,2, shinji naito6, ellen Knevels7,8, peter Carmeliet7,8, toru Oga9, shuji Kaneko10, seiji suga1, toshiki nokami1, Jun-ichi Yoshida1 & Yasuo Mori1,2,5*

Oxygen (O2) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O2, it is critical to elucidate the molecular mechanisms responsible for O2 sens- ing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with differ- ent redox potentials reveals the capability of TRPA1 to sense O2. O2 sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O2-dependent inhibition on TRPA1 activity in normoxia, direct O2 action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O2-sensing mechanism mediated by TRPA1.