Involvement of opioidergic and dopaminergic systems in anti-nociceptive activity of ethanol leaf extract of Bridelia micrantha (Hochst.) Baill (euphorbiaceae)

Background: Bridelia micrantha (Hochst.) Baill (Euphorbiaceae) leaves are used in traditional African medicine for treatment of stomach aches, tapeworms, diarrhea and headaches.Objective: This study investigates the anti-nociceptive property of ethanol leaf extract of Bridelia micrantha (EBM) in mice.Methods: The ethanol leaf extract of Bridelia micrantha (EBM) (50, 100 and 200 mg/kg) was administered orally to Swiss albino mice. The antinociceptive effect was evaluated using acetic acid-induced writhing, formalin, hot plate and tail clip-induced nociception.Results: EBM (50, 100, 200 mg/kg) produced dose dependent and significant (p<0.05, p<0.01, p<0.001) increase in pain threshold with peak effect at 200 mg/kg. EBM (200 mg/kg) inhibited acetic acid-induced writhing by 74.24%, reduced formalin-induced neurogenic and inflammatory pain by 68.62% and 74.32% at early and late phase respectively. In addition, time course increase in reaction latency were observed in tail clip and hot plate tests, 44.80% (2 h) and 27.06% (1 h) maximum possible effect, respectively. However, the pretreated mice with naloxone (opioid receptor antagonist) had no effect on antinociception of EBM (68.62 %; 74.32%) while metoclopramide (dopamine D2- receptor antagonist) reversed the anti-nociception observed with EBM (25.66%; 34.53%) in formalin test, indicating the involvement of dopamine receptor. The LD50 of EBM was 2,258.53 mg/kg. Flavonoids, tannins, phlobatannins, and saponins were found to be present in EBM.Conclusion: Findings from this study suggest antinociceptive effect of EBM through peripheral and central mechanisms. This justifies the use of the plant in traditional medicine for the treatment of pain.Keywords: Intraperitoneal, analgesic, metoclopramide, naloxone, dopamine, opioi