Noxious heat threshold temperature and pronociceptive effects of allyl isothiocyanate (mustard oil) in TRPV1 or TRPA1 gene-deleted mice

Life Sci. 2016 Jun 1;154:66-74. doi: 10.1016/j.lfs.2016.04.030. Epub 2016 Apr 25.

Abstract

Aims: To investigate the roles of TRPV1 and TRPA1 channels in baseline and allyl isothiocyanate (AITC)-evoked nociceptive responses by comparing wild-type and gene-deficient mice.

Main methods: In contrast to conventional methods of thermonociception measuring reflex latencies, we used our novel methods to determine the noxious heat threshold.

Key findings: It was revealed that the heat threshold of the tail measured by an increasing-temperature water bath is significantly higher in TRPV1(-/-), but not TRPA1(-/-), mice compared to respective wild-types. There was no difference between the noxious heat thresholds of the hind paw as measured by an increasing-temperature hot plate in TRPV1(-/-), TRPA1(-/-) and the corresponding wild-type mice. The withdrawal latency of the tail from 0°C water was prolonged in TRPA1(-/-), but not TRPV1(-/-), mice compared to respective wild-types. In wild-type animals, dipping the tail or paw into 1% AITC induced an 8-14°C drop of the noxious heat threshold (heat allodynia) of both the tail and paw, and 40-50% drop of the mechanonociceptive threshold (mechanical allodynia) of the paw measured by dynamic plantar esthesiometry. These AITC-evoked responses were diminished in TRPV1(-/-), but not TRPA1(-/-), mice. Tail withdrawal latency to 1% AITC was significantly prolonged in both gene-deleted strains.

Significance: Different heat sensors determine the noxious heat threshold in distinct areas: a pivotal role for TRPV1 on the tail is contrasted with no involvement of either TRPV1 or TRPA1 on the hind paw. Noxious heat threshold measurement appears appropriate for preclinical screening of TRP channel ligands as novel analgesics.

Keywords: Allodynia; Mustard oil; Noxious heat threshold; TRPA1; TRPV1.

MeSH terms

  • Animals
  • Hot Temperature*
  • Isothiocyanates / pharmacology*
  • Mice
  • Mice, Knockout
  • TRPA1 Cation Channel
  • TRPV Cation Channels / genetics*
  • Transient Receptor Potential Channels / genetics*

Substances

  • Isothiocyanates
  • TRPA1 Cation Channel
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • allyl isothiocyanate