Participation of the spinal TRPV1 receptors in formalin-evoked pain transduction: a study using a selective TRPV1 antagonist, iodo-resiniferatoxin

Abstract

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.

Botulinum toxin type A selectivity for certain types of pain is associated with capsaicin-sensitive neurons

“…-BoNT/A and TRPV1 receptor antagonists reduce formalin-induced pain [15,18,34,39,41,59,63]. However, in present experiments, 2.5% formalin-induced nocifensive response was unaltered by i.g.…”

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

“…We used capsazepine, a blocker for both TRPM8 and TRPV1 receptors, for behavioral assessment because no selective TRPM8 antagonist is currently available (Weil et al, 2005). Although capsazepine attenuated cold allodynic responses in the CCI animals, I-RTX, a potent TRPV1 antagonist (Seabrook et al, 2002;Correll et al, 2004;Kanai et al, 2006) that had no inhibitory effect on TRPM8, did not show a similar effect. This suggests that the effect of capsazepine was not attributable to its inhibition to TRPV1.…”

“…To examine whether or not the inhibition of TRPV1 receptors accounted for the suppression of cold allodynic responses by capsazepine, we tested I-RTX, a TRPV1 antagonist that is ϳ1000 times more potent than capsazepine (Seabrook et al, 2002;Correll et al, 2004;Kanai et al, 2006), to see whether it might produce an inhibitory effect similar to capsazepine. We did not find any significant difference in the acetone test on the CCI rats before and after I-RTX treatment (0.75 mg/kg; n ϭ 4) ( Fig.…”

Membrane-Delimited Coupling of TRPV1 and mGluR5 on Presynaptic Terminals of Nociceptive Neurons

“…Indeed, both spinal mGluR5 and TRPV1 have been demonstrated to contribute to pain hypersensitivity under pathological pain conditions (Caterina et al, 2000;Walker et al, 2001a;Zhu et al, 2005;Kanai et al, 2006). Whereas a functional role for mGluR5 in superficial dorsal horn neurons (i.e., postsynaptic neurons) has recently been demonstrated (Hu et al, 2007), relatively little is known about how presynaptic mGluR5 contributes to nociceptive synaptic transmissions in the spinal dorsal horn.…”