Withania somnifera (L.) Dunal root extract alleviates formalin-induced nociception in mice: involvement of the opioidergic system.

Withania somnifera (L.) Dunal extracts (WSEs) may possess therapeuticperspectives in the treatment of inflammation and pain. We aimed to evaluate the antinociceptive property of a WSE in the formalin test and to investigate theinvolvement of several neurotransmitter systems in this effect. The time spentlicking the formalin-injected paw was recorded in CD1 mice after pretreatmentwith increasing doses of WSE. Also, c-Fos spinal cord expression and the effects of different compounds were investigated under these experimental conditions.Finally, the efficacy of WSE was analyzed following an injection of glutamate.WSE reduced the antinociceptive response during the tonic but not the acute phaseof the formalin test and decreased formalin-induced c-Fos expression in spinalneurons. These effects were antagonized by the opioid antagonist naltrexone,whereas GABA, cannabinoid, ?-opioid, and nitric oxide compounds were ineffective.The administration of WSE also reduced nociception and c-Fos expression inducedby glutamate injection. These results showed that WSE is effective in assays ofchemical-induced nociception, indicating that this plant has potential valuableproperties for the treatment of specific painful conditions. The antinocicetiveeffects of WSE in the formalin test appeared to be specifically mediated by theopioidergic system, although the involvement of the glutamatergic system cannotbe excluded.