Tramadol, Alpha-2 Adrenalin Receptor Subtype and Neuropathic Rat Model

Abstract

Spinally administered α2-adrenergic agonists show analgesic effects in normal and neuropathic states. Their effects are mediated via α2-adrenoceptors. Plasticity of nervous system after nerve injury can change the expressions of the related receptors in spinal cord. The expression of α2-adrenoceptor subtypes in spinal cord and the effect of chronic systemic administration of tramadol was probed in neuropathic rat pain model. Methods: Sprague-Dawley rats were prepared to make neuropathic pain model by L5 and L6 spinal nerve ligation. Withdrawal threshold for tactile allodynia was evaluated with von Frey hair throughout experiment. Tramadol (15 mg/kg) or equivalent volume of saline was injected intraperitoneally twice a day for 21 days. In the 14th day and 21st day, allodynia and the systemic effect of tramadol was measured and compared with control group. At the 21st day, rat spinal cords were harvested and the expression of α2-adrenoceptor subtypes were measured and compared with real time PCR. Results: Chronic administration of tramadol did not improve the allodynia nor the effect of tramadol in spinal nerve ligation model. The mRNA of α2A-adrenoceptor in nerve injury site decreased compared to controlateral site. The mRNA of α2C-adrenoceptor subtype in nerve injury rat decreased compared with normal animal, and chronic administration of tramadol increased it compared to saline group. Conclusions: Rats with neuropathic pain by spinal nerve ligation showed the expression of α2-adrenoceptors subtypes in spinal cord, and chronic systemic administration of tramadol may influence the expression of α2-adrenoceptors subtypes.