Activation of the Akt signaling pathway alleviates ropivacaine-induced myelination impairment of the spinal cord and hypoalgesia in neonatal rats

Abstract Prolonged exposure to local anesthetics (LAs) or intrathecal administration of high doses of LAs can cause spinal cord damage. Intraspinal administration of LAs is increasingly being used in children and neonates. Therefore, it is important to study LA-related spinal cord damage and the underlying mechanism in developmental models. First, neonatal Sprague–Dawley rats received three intrathecal injections of 0.5%, 1%, or 2% ropivacaine or saline (90 min interval) on postnatal day (P)7. The electron microscopy and behavioral tests were performed to evaluate the neurotoxic effects of ropivacaine at different concentrations on spinal cord in rats. Western blot analysis was performed to measure the expression levels of p-Akt, Akt, myelin gene regulatory factor (MYRF) and myelin basic protein (MBP) in the spinal cord following administration of 2% ropivacaine. Our results showed that ropivacaine impaired myelination in the spinal cord and induced hypoalgesia in a dose-dependent, whereas 0.5% ropivacaine did not cause spinal cord damage in neonatal rats. Moreover, 2% ropivacaine decreased the expression of p-Akt, MYRF and MBP in the spinal cord. Then, the Akt-specific activator (SC79) was intraperitoneally injected 30 min before 2% ropivacaine treatment. Interestingly, SC79-mediated activation of the Akt signaling pathway alleviated ropivacaine-induced the impairment of myelination in the spinal cord and hypoalgesia. Overall, the results showed that ropivacaine caused spinal cord damage in a dose-dependent manner in neonatal rats and that activation of the Akt signaling pathway alleviated these ropivacaine-induced changes. These data provide insight into the damage to the developing spinal cord caused by LAs.