Valnoctamide; The effect on relieving of neuropathic pain and possible mechanisms

Antidepressants and anticonvulsants are recommended as first step treatment of neuropathic pain. Valnoctamide, an amide derivative of valproic acid, is one of the anticonvulsant agents that are predicted to be potential to use in management of pain. Even though the studies demonstrated the anti-allodynic effect of this drug, possible antihyperalgesic activity and mechanism of action has not yet been clarified. In this study, it is aimed to assess the possible anti-allodynic and antihyperalgesic effect of valnoctamide at the doses of 40, 70 and 100 mg/kg (i.p.) in neuropathic pain model induced by chronic constriction injury in rats, by using dynamic plantar test and plantar test (Hargreaves method) and to investigate that the possible role of serotonergic, noradrenergic, opioidergic and GABAergic mechanisms by pre-treatment with 1 mg/kg (i.p.) ketanserin, yohimbine, naloxone and 0.5 mg/kg (i.p.) bicuculline, respectively. 70 and 100 mg/kg valnoctamide significantly (P<0.01, P<0.001) increased the mechanical and thermal thresholds decreasing with the development of neuropathy and demonstrated anti-allodynic and antihyperalgesic activity. Limited contribution of serotonergic, noradrenergic and opioidergic systems and significant (P<0.001) contribution of GABAergic system to the anti-allodynic activity have been identified whereas limited contribution of opioidergic and GABAergic systems and significant (P<0.01, P<0.05) contribution of serotonergic and noradrenergic systems to the antihyperalgesic activity have been identified. On the basis of these results and considering that valnoctamide has safer side-effect profile, it is possible to say that valnoctamide is a potential agent that might be used alone or in combination with the other effective therapies in the alleviating of neuropathic pain.