BackgroundHybanthus enneaspermus (HE) leaves are being used traditionally to relieve pain, and scientific studies have demonstrated their analgesic potential. This study attempted to elucidate the pharmacological mechanism(s) involved in the analgesic action of ethanol extract of H. enneaspermus leaves (EEHE).Materials and methodsForty-two male Wistar rats were separately randomized into seven groups (n=6 rats in each group) for tail immersion and formalin tests. Group I (control) received distilled water (10 mL/kg) while groups II and III received acetaminophen (the reference drug, 100 mg/kg ip) and EEHE (1000 mg/kg po), respectively. Groups IV–VII were pretreated with cimetidine (50 mg/kg ip), naloxone (5 mg/kg ip), propranolol (0.15 mg/kg ip), and prazosin (0.15 mg/kg ip), respectively, 1 hour before EEHE (1000 mg/kg po) treatment.ResultsThe EEHE-induced increase in tail-flick latency was reduced by blockade of histamine and adrenergic receptors but prevented by blockade of opiate receptor in the tail-flick test. However, the EEHE-induced decrease in paw licking time was prevented only by blockade of opiate receptor but unaffected by histamine and adrenergic receptors blockers.ConclusionThese findings suggest that the analgesic effect of EEHE in different pain types may involve different neural mechanisms and that the opioidergic pathway contributes more to EEHE-induced analgesia than the other pathways.