Elucidation of the Possible Mechanism of Antinociceptive Action of Methanol Stem Bark Extract of Zanthoxylum gilletii (De Wild.) in Mice

Background and Purpose: Zanthoxylum gilletii (De Wild.) stem bark is used traditionally for pain management, but its antinociceptive activity is yet to be validated. This study evaluated the antinociceptive activity and elucidated the possible mechanism of antinociceptive action of its methanol stem bark extract. Methods: Oral acute toxicity was evaluated using Lorke’s method, while antinociceptive activity was assessed using acetic acid-induced writhing test. Mice were randomly assigned to groups receiving distilled water, morphine (10 mg/kg), or the extract (250 and 500 mg/kg). Mechanistic studies involved pre-treating mice with naloxone (2 mg/kg), glibenclamide (5 mg/kg), or propranolol (20 mg/kg) 15 min before the extract (500 mg/kg), followed by acetic acid administration. Results: No mortality or signs of toxicity were observed at acute oral doses up to 5,000 mg/kg. The extract significantly (P<0.01) reduced writhing counts in a dose-dependent manner, with effects reversed by naloxone (P<0.05), enhanced by propranolol and unaffected by glibenclamide. Conclusion: Zanthoxylum gilletii extract has a high oral safety margin, with an LD?? exceeding 5,000 mg/kg. The antinociceptive activity of the extract may involve opioid receptor activation, but not beta-adrenergic pathway or ATP-sensitive potassium channels. Further studies would determine its bioactive components.