Evaluation of Antinociceptive and Neurotoxic Effects of Intrathecal Dexmedetomidine in Rats

Abstract

Objective: Dexmedetomidine has been reported to produce analgesia after intrathecal administration. In the present study the alpha 2-adrenoceptor agonist dexmedetomidine was evaluated for its potential spinal neurotoxic effects. Material and Methods: Three days after intrathecal cannulation, rats were administered either dexmedetomidine (3 mu g/30 mu L, i.t.) or saline (30 mu L, i.t.). Antinociceptive, sedative and motor effects of intrathecal administrations of dexmedetomidine or saline were evaluated during 90 min. The tail-flick and hot plate tests were used to assess the thermal nociceptive threshold. Seven days after drug administration, animals were sacrified and spinal cords were evaluated for histopathological changes by light microscopy. Results: Dexmedetomidine administered intrathecally produced antinociception. Antinociception was accompanied by immediate sedation and loss of placing-stepping reflexes that lasted over 40 min in all dexmedetomidine administered rats. In all rats, microscopic examination revealed mild gliosis and minimal infiltration of inflamatory r cells in posterior white matter. Mild (total score 4-6) histopathologic lesions were seen in four animals in dexmedetomidine adminisered rats, but there was no statistically significant difference when compared with the saline administered rats. Conclusion: We observed that intrathecal injections of dexmedetomidine at the dose of 3 mu g/30 mu L produce antinociception but did not cause any histopathological sign of injury in the spinal cord.