Anti-hyperalgesic and anti-nociceptive Effects of the Aqueous and Ethanol Extracts of Keetia venosa fruits on acute and chronic pain Models induced in rats and mice.

Abstract

Abstract: Background: Keetia venosa also called Canthium venosum is a medicinal plant used in Cameroon traditional medicine to treat ailments such as pain. Aim: This study was undertaken to evaluate both antihyperalgesic and the anti-nociceptive effects of the aqueous and ethanol extracts from the fruit of Keetia venosa Methods: Inflammatory pain was induced by subplantar injection of 100 µl of CFA in rats. Both extracts were administered orally at the doses of 50, 100 and 200 mg/kg/ day, their antihyperalgesic effects were follow in acute and chronic treatment. Oxidative stress parameters (NO, MDA and glutathione) were measured at the level of left and right brain and spinal cord of rats. Also, specific tests such as formalin, allyl isothiocyanate, mechanical and cold allodinya were conducted to evaluate mechanism of action of the extracts. Results: The acute and chronic administration of aqueous and ethanol extracts at all the doses significantly (P<0.05, P<0.01and P<0.001) increased pain threshold on mechanical hyperalgesia induced by analgesimeter on CFA-induced pain model. Both extracts at all doses significantly (P<0.05, P<0.01and P<0.001) , reduced neurogenic and inflammatory pain induced by formalin with higher effect(50.26 and 77.77%) observed for the neurogenic phase with the aqueous extract at the dose of 100 mg/kg, and for the inflammatory phase with the ethanol extract at the same dose respectively. Moreover, giving orally, both extracts significantly inhibited pain induced by allyl isothiocyanate (dose dependant manner for ethanol extract) as well as reduced hypersensitivity provoked by acetone (dose dependant manner) and von Frey hair in the same pain model. Subsequenty, the ethanol extract on oxidative stress parameters significantly (P<0.05 and P<0.001) and in dose dependant manner reduced the NO level in the right brain and also significantly (P<0.05) increase the level of glutathione in same hemisphere. Conclusion: The antihypernociceptive and antinociceptive effect observed after oral administration of Aqueous and methanol extracts from Keetia venosa fruits seem to be mediated through the inactivation of TRP (TRPA1 and TRPM8) and decreasing of NO level. This may justify the use in Cameroonian folke medicine. Keywords: Keetia venosa, anti-hyperalgesia, Aqueous and ethanol extract, Nitric oxide, glutathione, TRP.