Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy

Neuropathic pain. due to peripheral nerve damage, can include allodynia (pe rception of innocuous stimuli as being painful), hyperalgesia (increased se nsitivity to noxious stimuli) and spontaneous pain. often accompanied by se nsory deficits. Plasticity in transmission and modulatory systems are impli cated in the underlying mechanisms. The Kim and Chung rodent model of neuro pathy (Kim and Chung, Pain 50 (1992) 355) employed here involves unilateral tight ligation of two (L5 and L6) of the three (L4, L5, and L6) spinal ner ves of the sciatic nerve and reproducibly induced mechanical and cold allod ynia in the ipsilateral hindpaw over the 14 day post-operative period. In v ivo electrophysiological techniques have then been used to record the respo nse of dorsal horn neurones to innocuous and noxious electrical and natural (mechanical and thermal) stimuli after spinal nerve ligation (SNL). Activa tion of voltage-dependent calcium channels (VDCCs) is critical for neurotra nsmitter release and neuronal excitability, and antagonists can be antinoci ceptive. Here, for the first time, the effect of N- and P-type VDCC antagon ists: (omega -conotoxin-GVIA and omega -agatoxin-IVA, respectively) on the evoked dorsal horn neuronal responses after neuropathy have been investigat ed. Spinal omega -conotoxin-GVIA (0.1-3.2 mug) produced prolonged inhibitio ns of both the electrically- and low- and high-intensity naturally-evoked n euronal responses in SNL and control rats. Spinal w-agatoxin-IVA (0.1-3.2 m ug) also had an inhibitory effect but to a lesser extent. After neuropathy the potency of omega -conotoxin-GVIA was increased at lower doses in compar ison to control. This indicates an altered role for N-type but not P-type V DCCs in sensory transmission after neuropathy and selective plasticity in t hese channels after nerve injury. Both pre- and post-synaptic VDCCs appear to be important. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.