The involvement of spinal transient receptor potential vanilloid 1 (TRPV1) in
formalin-evoked
pain has remained unclear, because investigation of this kind of
pain with selective antagonists has not been conducted. The purpose of this study is to investigate the participation of spinal TRPV1 in
formalin-evoked
pain with
iodo-resiniferatoxin (I-RTX), a potent TRPV1-selective antagonist. I-RTX given intrathecally dose-dependently and significantly decreased the number of flinching responses in the
formalin-evoked 1st and 2nd phase with ID50 values (
drug dose producing 50% inhibition of response) of 1.0 and 3.8 microg, respectively, and concentration-dependently suppressed
capsaicin-evoked
calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) release from rat spinal cord slices with an IC50 value (
drug concentration producing 50% inhibition of response) of 86 nM.
Capsazepine, a classical non-selective TRPV1 antagonist, given intrathecally also inhibited
formalin-evoked flinching in both the 1st and 2nd phase with ID50s of 420 and 200 microg, respectively, and CGRP-LI release from rat spinal cord slices with an IC50 of 7.8 microM. Ratios of in-vivo
analgesic potencies of I-RTX and
capsazepine well reflected their intrinsic in-vitro activity. These findings suggest that spinal TRPV1 participates in the transduction system of
formalin-evoked
pain.