Potentiation of the antinociceptive effect of clomipramine by a 5-ht(1A) 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 serotoninerg ic antidepressant reduced the delay of action and increases the thymoanalep tic effect of the drug. 2 The purpose of this work was to evaluate the combination of an antidepres sant and a 5-HT1A antagonist in animal models of chronic neuropathic pain. We studied the antinociceptive effect of the co-administration of clomipram ine 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 di abetic rats). 3 The results show an increase in the antinociceptive effect of acutely inj ected clomipramine due to WAY 100,635 in these models, which is majored whe n the two drugs are repeatedly injected. The 5-HT1A antagonist reduced the delay of onset and increased the maximal antinociceptive effect of clomipra mine. 4 These new findings argue for using the combination of an antidepressant a nd a 5-HT1A antagonist in human neuropathic pain therapy.