Potentiation of the antinociceptive effect of clomipramine by a 5-ht1A antagonist in neuropathic pain in rats

1 The benefit of antidepressant treatment in human neuropathic pain is now well documented, but the effect is limited and slow to appear. It has been demonstrated that the association of a 5-HT1A antagonist and a serotoninergic antidepressant reduced the delay of action and increases the thymoanaleptic effect of the drug. 2 The purpose of this work was to evaluate the combination of an antidepressant and a 5-HT1A antagonist in animal models of chronic neuropathic pain. We studied the antinociceptive effect of the co-administration of clomipramine and a 5-HT1A antagonist (WAY 100,635) in a pain test applied in normal rats and in two models of neurogenic sustained pain (mononeuropathic and diabetic rats). 3 The results show an increase in the antinociceptive effect of acutely injected clomipramine due to WAY 100,635 in these models, which is majored when the two drugs are repeatedly injected. The 5-HT1A antagonist reduced the delay of onset and increased the maximal antinociceptive effect of clomipramine. 4 These new findings argue for using the combination of an antidepressant and a 5-HT1A antagonist in human neuropathic pain therapy.