Synergy between intrathecal ω-conotoxin CVID and dexmedetomidine to attenuate mechanical hypersensitivity in the rat

The analgesic effects of intrathecal (i.t.) ω-conotoxin CVID, an N-type Ca2+ channel antagonist, and the α2-adrenoceptor agonist, dexmedetomidine, were tested alone and in combination following unilateral ligation of L (lumbar) 5/6 spinal nerves in rats. Mechanical allodynia was observed prior to insertion of an i.t. catheter. Effects and interactions of ω-conotoxin CVID (0.01-10 μg/kg) and dexmedetomidine (0.1-10 μg/kg) were tested on allodynic and tail flick (thermal stimulus) responses. Only dexmedetomidine increased the latency of the tail flick response. Both dexmedetomidine and ω-conotoxin CVID completely inhibited allodynia (ED50 0.78±0.02 and 0.35±0.08 μg/kg, respectively; n=63, 41). Dexmedetomidine and ω-conotoxin CVID combined in dose ratios 0.7 and 1.3 (adjusted for ED50) were synergistic in decreasing mechanical hypersensitivity; interaction index (γ) 0.39 (confidence interval [CI] 0.33, 0.46) and 0.3 (CI 0.23, 0.38). Despite the necessity for i.t. administration, these data suggest that the synergistic combination confers enhanced potency (lower doses) of both drugs that may avoid clinical toxicity of single drug therapy.