The aim of this research was to assess the antinociceptive activity of the transient receptor potential (TRP) channel TRPV1, TRPM8, and TRPA1 antagonists in neurogenic, tonic, and
neuropathic pain models in mice. For this purpose, TRP channel antagonists were administered into the dorsal surface of a hind paw 15 min before
capsaicin,
allyl isothiocyanate (
AITC), or
formalin. Their antiallodynic and antihyperalgesic efficacies after intraperitoneal administration were also assessed in a
paclitaxel-induced
neuropathic pain model. Motor coordination of
paclitaxel-treated mice that received these TRP channel antagonists was investigated using the rotarod test. TRPV1 antagonists,
capsazepine and SB-366791, attenuated
capsaicin-induced nociceptive reaction in a concentration-dependent manner. At 8 µg/20 µl, this effect was 51% (P<0.001) for
capsazepine and 37% (P<0.05) for SB-366791. A TRPA1 antagonist,
A-967079, reduced
pain reaction by 48% (P<0.05) in the
AITC test and by 54% (P<0.001) in the early phase of the
formalin test. The test compounds had no influence on the late phase of the
formalin test. In
paclitaxel-treated mice, they did not attenuate heat
hyperalgesia but N-(3-aminopropyl)-2-{[(3-methylphenyl)methyl]oxy}-N-(2-thienylmethyl)
benzamide hydrochloride
salt (AMTB), a TRPM8 antagonist, reduced cold
hyperalgesia and
tactile allodynia by 31% (P<0.05) and 51% (P<0.01), respectively.
HC-030031, a
TRPA1 channel antagonist, attenuated
tactile allodynia in the von Frey test (62%; P<0.001). In conclusion, distinct members of TRP channel family are involved in different
pain models in mice. Antagonists of TRP channels attenuate nocifensive responses of neurogenic, tonic, and
neuropathic pain, but their efficacies strongly depend on the
pain model used.