Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception

S. Bang, S. Yoo, T. J. Yang, H. Cho, Y. G. Kim, S. W. Hwang

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE Temperature-sensitive transient receptor potential ion channels (thermoTRPs) expressed in primary sensory neurons and skin keratinocytes play a crucial role as peripheral pain detectors. Many natural and synthetic ligands have been found to act on thermoTRPs, but little is known about endogenous compounds that inhibit these TRPs. Here, we asked whether resolvin D1 (RvD1), a naturally occurring anti-inflammatory and pro-resolving lipid molecule is able to affect the TRP channel activation. EXPERIMENTAL APPROACH We examined the effect of RvD1 on the six thermoTRPs using Ca 2+ imaging and whole cell electrophysiology experiments using the HEK cell heterologous expression system, cultured sensory neurons and HaCaT keratinocytes. We also checked changes in agonist-specific acute licking/flicking or flinching behaviours and TRP-related mechanical and thermal pain behaviours using Hargreaves, Randall-Selitto and von Frey assay systems with or without inflammation. KEY RESULTS RvD1 inhibited the activities of TRPA1, TRPV3 and TRPV4 at nanomolar and micromolar levels. Consistent attenuations in agonist-specific acute pain behaviours by immediate peripheral administration with RvD1 were also observed. Furthermore, local pretreatment with RvD1 significantly reversed mechanical and thermal hypersensitivity in inflamed tissues. CONCLUSIONS AND IMPLICATIONS RvD1 was a novel endogenous inhibitor for several sensory TRPs. The results of our behavioural studies suggest that RvD1 has an analgesic potential via these TRP-related mechanisms.

Original languageEnglish
Pages (from-to)707-720
Number of pages14
JournalBritish Journal of Pharmacology
Volume161
Issue number3
DOIs
Publication statusPublished - 2010 Oct

Keywords

  • Resolvin D1
  • TRPA1
  • TRPV3
  • TRPV4
  • inflammation
  • keratinocytes
  • nociceptive behaviours
  • pain
  • sensory neurons

ASJC Scopus subject areas

  • Pharmacology

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