Evaluation of the neurotoxic effects of intrathecal administration of (S)-(+)-Ketoprofen on rat spinal cords: randomized controlled experimental study

Abstract

Background and objectives: Intrathecal administration of non-steroidal anti-inflammatory drugs is more efficacious for post-operative pain management. Cyclooxygenase inhibiting nonsteroidal anti-inflammatory drugs like (S)-(+)-Ketoprofen, may be effective at lower intrathecal doses than parenteral ones. Preclinical safety regarding possible neurotoxicity associated with the intrathecal (S)-(+)-Ketoprofen was not evaluated. Here we analysed the neurotoxicity of intrathecally administered (S)-(+)-Ketoprofen in rats. Methods: A randomized placebo-controlled experimental study was conducted. SpragueDawley rats (250-300g) aged 12-16 weeks were randomly divided into 2 treatments [100 and 800 mu g (S)-(+)-Ketoprofen] and control (sterile water) groups. Intrathecal catheters were placed via the atlantoaxial space in anesthetized rats. Pinch-toe tests, motor function evaluations and histopathological examinations of the spinal cord and nerve roots were performed at days 3, 7 and 21. Spinal cord sections were evaluated by light microscopy for the dorsal axonal funiculus vacuolation, axonal myelin loss, neuronal chromatolysis, neuritis, meningeal inflammation, adhesions, and fibrosis. Results: Rats in all the groups exhibited normal pinch-toe testing response (score = 0) and normal gait at each observed time (motor function evaluation score =1). Neurotoxicity was higher with treatments on days 3 and 7 than that on day 21 (2, 3, 0, p =0.044; 2, 5, 0, p =0.029, respectively). On day 7, the total scores reflecting neuronal damage were higher in the 800 mu g group than those in the 100 mu g and Control Groups (5, 3, 0, p= 0.048, respectively). Conclusion: Intrathecal (S)-(+)-Ketoprofen caused dose-dependent neurohistopathological changes in rats on days 3 and 7 after injection, suggesting that (S)-(+)-Ketoprofen should not be intrathecally administered. (C) 2019 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda.