Anti-nociceptive Effect of Euphorbia hirta Leaf Extract: Involvement of Adenosine, Cholinergic, and Opioid Receptors.

Objective: The study was designed to investigate the anti-nociceptive activity of Euphorbia hirta leaf and its possible mechanism of action.

Methods: The extract of Euphorbia hirta obtained from the leaf was prepared as per standard procedures and evaluated at the three doses (300, 600, and 1200 mg/kg, i.p). The extract was screened for anti-nociceptive activity using heat-induced (tail-flick) and chemical-induced (acetic acid-induced writhing and formalin-induced paw lick) nociception models in mice. The possible mechanism of action of the extract was evaluated using antagonists of notable nociceptive pathways.

Results: Intraperitoneal administration of Euphorbia hirta extract at the doses of 600 and 1200 mg/kg significantly (p<0.05) reduced the formalin-induced paw licking in both neurogenic and inflammatory phases of the test. While administration of the extract at the dose of 300 mg/kg significantly inhibited the pain due to formalin in the inflammatory phase but not in the neurogenic phase. The anti-nociceptive effect of Euphorbia hirta extract increased the reaction time to thermal stimulus, also inhibited the acetic acid-induced writhing dose-dependently. The antinociceptive effect exhibited by Euphorbia hirta extract in the formalin test was reversed by the administration of naloxone, theophylline, and atropine. Glibenclamide, nifedipine, and yohimbine, however, did not significantly block the anti-nociceptive effect of the extract. Meanwhile, methylene blue administration enhanced the anti-nociceptive effect of the extract.

Conclusion: The results indicated that Euphorbia hirta extract produces a dose-related antinociceptive effect in several models of chemical and thermal pain, through mechanisms that might involve interaction with adenosine, cholinergic, and opioid receptors.