Possible mechanisms involved in the anti-nociceptive effects of hydro-ethanolic leaf extract of Ziziphus abyssinica

Context: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to support the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. Purpose: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE. Materials and methods: The effect of EthE (30, 100 and 300mg/kg) on intraplantar injection of pain mediators such as interleukin-1 beta, tumour necrosis factor-alpha, prostaglandin E-2 and bradykinin was evaluated in male Sprague Dawley rats using Randall-Selitto test for 5h. The effect of specific antagonists to the opioidergic, adenosinergic, ATP-sensitive K+ channels, nitric oxide, serotonergic, muscarinic, adrenergic and voltage-gated calcium channel on the anti-nociceptive effect of EthE (100mg/kg) was evaluated using the formalin test in male imprinting control region (ICR) mice for 1h. Results: Pretreatment of the rats with EthE significantly reversed the hypernociception induced by intraplantar injection of TNF-alpha (F-4,F-120=10.86, p<0.0001), IL-1 beta (F-4,F-120=14.71, p<0.0001), bradykinin (F-4,F-80=12.52, p<0.0001) and prostaglandin E-2 (F-5,F-144=6.165, p=0.0001). The anti-nociceptive effect exhibited by EthE in the formalin test was reversed by systemic administration of N-G-l-nitro-arginine methyl ester, naloxone, theophylline and glibenclamide. Conclusions: EthE inhibits hypernociception induced by TNF-alpha IL-1 beta bradykinin and prostaglandin E-2. EthE exhibited anti-nociceptive effects possibly mediated through opioidergic, adenosinergic, ATP-sensitive potassium channels and nitric oxide cyclic GMP pathways.