Analgesic and anti-inflammatory actions of Alafia barteri: Involvement of monoaminergic, nitrergic and opioidergic pathway.

Abstract

Background: We have earlier reported the antinociceptive and anti-inflammatory effects of Alafia barteri Oliver (Apocynaceae) in rodents but its mechanism of actionsare yet to be elucidated.
Objective: This study sought toinvestigate the involvement of monoaminergic, nitric oxide-cyclic GMP-K⁺ channel and opioidergic pathways in its mechanism of actions.
Methods: methanol root extract of Alafia barteri (ALA) (100-400 mg/kg, p.o.) was given 1 h before administration of chemical or thermal - induced nocicept ion andhistamine/serotonin-induced inflammation. Themechanism of the antinociceptive effect was investigated through intraperitoneal injection of prazosin (62.5 μg/kg; á adrenoceptor antagonist), yohimbine (1 1- mg/kg; á adrenoceptor antagonist) NG-nitro-L-arginine (L- 2 , NNA) (20 mg/kg; nitric-oxide-synthase inhibitor), cyproheptadine(10mg/kg;5-HTR2antagonist),glibenclamide (10 mg/kg; ATP-sensitive K⁺- channel inhibitor), or naloxone (5 mg/kg; opioid-receptor antagonist) before the nociceptive models.
Results: ALA(100-400 mg/kg)treatment produced dose and time dependent (P<0.001; 87.11%)increase in pain threshold in acetic acid-induced-writhing, inhibition ofneurogenic (50.96%), and inflammatory (70.02%) phases of formalin test, and 41.75% maximum possible effect (MPE) in tail immersion testat 400 mg/kg in comparison with vehicle-treated control. The antinociceptive-effect was blocked by pretreatmentof mice withprazosin, yohimbine or L-NNA, (P<0.001) in writhingassay. Similarly, naloxone pretreatment blocked the inhibition of neurogenic- and inflammatory-pain induced by ALA in formalin test. Interestingly, ALA produced dose related time course inhibition (P<0.05) of histamine and serotonin-induced paw inflammation with peak effects (57.89, and 81.82%), respectively, at 400 mg/kg.
Conclusion: Findings from these studies suggest central and peripheral analgesic effect of A. barteri through interaction with L-arginine-nitric-oxide pathway, á - 1/2 adrenoceptors, and/or, opioidergic pathway, while, the antiinflammatory
effect involves marked inhibition of histamine and serotonin release.

Keywords: á-adrenoceptor; ATP-sensitive potassium channel; histamine; opioidergic ;pathway; serotonin; formalin-induced nociception.