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

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 nociception andhistamine/serotonin-induced inflammation. The mechanism of the antinociceptive effect was investigated through intraperitoneal injection of prazosin (62.5 pg/kg; alpha1-adrenoceptor antagonist), yohimbine (1 mg/kg; alpha2 adrenoceptor antagonist) N(G)-nitro-L-arginine (L-NNA) (20 mg/kg; nitric-oxide-synthase inhibitor), c y p r o h e p t a d i n e (10 mg/kg; 5-HT2R antagonist), 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 of neurogenic (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 writhing-assay. 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 arralgesic effect of A. barteri through interaction with L-arginine-nitric-oxide pathway, alpha(1/2)-adrenoceptors, and/or, opioidergic pathway, while, the anti-inflammatory effect involves marked inhibition of histamine and serotonin release.