Involvement of opioid, adenosine and 5-HT3 receptors in antinociceptive effects of an ayurvedic polyherbal formulation

ABSTRACT

The present study was undertaken to evaluate the antinociceptive effects of an ayurvedic polyherbal formulation in rats and mice employing the tail immersion test and acetic acid-induced writhing test, respectively. With the tail immersion method, rats received two different doses [270 and 405 mg/kg BW, p.o.] of a formulation, pethidine [5.4 mg/kg BW, p.o.] as a reference standard and the combination of the higher dose of the formulation with naloxone [2 mg/kg, i.p.], an opioid receptor antagonist, and caffeine [16 mg/kg, i.p.], used as an adenosine receptor antagonist. In the acetic acid-induced writhing test, mice received two different doses [390 and 585 mg/kg, BW, p.o.] of formulation, diclofenac sodium [15 mg/kg, BW, p.o.] as a reference standard and the combination of the higher dose of the polyherbal formulation with ondansetron [0.5 mg/kg, i.p.], a serotonin receptor antagonist. The polyherbal formulation [405 mg/kg] exhibited a significant [p < 0.01] antinociceptive effect using the tail immersion method. In the acetic acid-induced writhing test, the formulation showed significant [p < 0.01] dose-dependent activity. The antinociceptive effect of the polyherbal formulation apparently involved an opiate-like mechanism, since its antinociceptive action was attenuated by naloxone pretreatment. In addition, antinociceptive activity was attenuated by caffeine and reversed by ondansetron pretreatment. Our data suggest that the polyherbal formulation possessed centrally and peripherally mediated antinociceptive properties. The activity could be mediated through opioid, adenosine, and serotonin receptors and via inhibition of cyclo-oxygenase- and/or lipoxygenase-dependent pathways