TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hypersensitivity after muscle inflammation

Roxanne Y. Walder, Rajan Radhakrishnan, Lipin Loo, Lynn A. Rasmussen, Durga P. Mohapatra, Steven P. Wilson, Kathleen A. Sluka

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Inflammatory thermal hyperalgesia is principally mediated through transient receptor potential vanilloid 1 (TRPV1) channels, as demonstrated by prior studies using models of cutaneous inflammation. Muscle pain is significantly different from cutaneous pain, and the involvement of TRPV1 in hyperalgesia induced by muscle inflammation is unknown. We tested whether TRPV1 contributes to the development of mechanical and heat hypersensitivity of the paw in TRPV1-/- mice after muscle inflammation. Because TRPV1-/- mice lack TRPV1 at the site of inflammation (muscle) and at the testing site (paw), we do not know whether TRPV1 is important as a mediator of nociceptor sensitization in the muscle or as a heat sensor in the paw. Using recombinant herpesviruses, we reexpressed TRPV1 in TRPV1-/- mice in primary afferents innervating skin, muscle, or both to determine which sites were important for the behavioral deficits. Responses to repeated application of noxious mechanical stimuli to the hind paw were enhanced in TRPV1-/- mice; this was restored by reexpression of TRPV1 into skin. Withdrawal latencies to noxious heat were increased in TRPV1-/- mice; normal latencies were restored by reexpression of TRPV1 in both skin and muscle. Heat hypersensitivity induced by muscle inflammation did not develop in TRPV1 -/- mice; mechanical hypersensitivity was similar between TRPV1 -/- and TRPV1+/+ mice. Heat hypersensitivity induced by muscle inflammation was restored by reexpression of TRPV1 into both muscle and skin of TRPV1-/- mice. These results suggest that TRPV1 serves as both a mediator of nociceptor sensitization at the site of inflammation and as a heat sensor at the paw.

Original languageEnglish
Pages (from-to)1664-1672
Number of pages9
JournalPain
Volume153
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • Mechanical hypersensitivity
  • Muscle inflammation
  • Muscle pain
  • Thermal hyperalgesia

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