The
analgesic effects of intrathecal (i.t.)
omega-conotoxin CVID, an N-type Ca2+ channel antagonist, and the alpha2-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
omega-conotoxin CVID (0.01-10 microg/kg) and
dexmedetomidine (0.1-10 microg/kg) were tested on allodynic and tail flick (thermal stimulus) responses. Only
dexmedetomidine increased the latency of the tail flick response. Both
dexmedetomidine and
omega-conotoxin CVID completely inhibited
allodynia (ED50 0.78+/-0.02 and 0.35+/-0.08 microg/kg, respectively; n=63, 41).
Dexmedetomidine and
omega-conotoxin CVID combined in dose ratios 0.7 and 1.3 (adjusted for ED50) were synergistic in decreasing mechanical
hypersensitivity; interaction index (gamma) 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.