Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include
allodynia (touch-evoked
pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in
voltage-dependent calcium channel (
VDCC) expression and function; however, the role of Ca(v)2.3
calcium channels has not clearly been defined. Here, the effects of
SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve
ligation (SNL) model of chronic
neuropathic pain [Kim & Chung, (1992)
Pain, 50, 355-363] was used to induce
mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to
sham-operated animals. Spinal
SNX-482 (0.5-4 microg/50 microL) exerted dose-related inhibitions of noxious C-fibre- and Adelta-fibre-mediated neuronal responses in conditions of neuropathy, but not in
sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to
SNX-482. In contrast, non-noxious Abeta-mediated responses were not affected by
SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to
SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3
calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.