Actions of intrathecal ω-conotoxins CVID, GVIA, MVIIA, and morphine in acute and neuropathic pain in the rat

Agents which decrease conductance of N-type voltage-gated Ca2+ channels have been shown to attenuate measures of neuropathic pain in animal models and to provide symptom relief in humans. The omega-conotoxins have demonstrated efficacy but have a low therapeutic index. We have investigated the effects of a new omega-conotoxin, CVID (AM-336), and compared them with omega-conotoxin GVIA (SNX- 124), omega-conotoxin MVIIA (SNX- 111) and morphine in a spinal nerve ligation model of neuropathic pain in the rat. The ED50 (and 95% Cl) for attenuation of tactile allodynia by intrathecal administration for (omega-conotoxin CVID, GVlA, MVIIA and morphine was 0.36 (0.27-0.48), 0.12 (0.06-0.24), 0.32 (0.23-0.45) and 4.4 (2.9-6.5) mug/kg, respectively. Only morphine significantly prolonged acute tail flick responses (ED50 2.3 (1.1-4.9) mug/kg). Of the omega-conotoxins, omega-conotoxin CVID showed the highest ratio of efficacy to behavioural toxicity. These observations show that intrathecal omega-conotoxins are effective in attenuating tactile allodynia in the rat without significantly affecting acute nociceptive responses. omega-Conotoxin CVID had similar potency to omega-conotoxin MVIIA but showed less toxicity in the therapeutic range. (C) 2002 Elsevier Science B.V. All rights reserved.