Association of opioids with non-opioid analgesics, like non-steroidal anti-inflammatory drugs and dypirone, and with local anesthetic techniques, characterizes the practice of "multimodal" analgesia. Unfortunately, in some cases of post-operatory or traumatic pain, or in cases related to neuropathic and oncological pain, in which central sensitization occurs, the response to those protocols could be not satisfactory. Ketamine had been used successfully in those patients. Epidural ketamine could be more advantageous than systemic ketamine because of the proximity to its targets in the spinal cord, the reduction of doses required to obtain analgesic effects, the longer duration of the effects and the minimal risk of systemic toxicity. Nevertheless, it has been reported a supposed neurotoxic effect of ketamine when injected by the neuraxial way. This neural toxicity was associated with the addition of preservatives and with the use of high concentrations of ketamine. There is no conclusive data about the real toxicity of ketamine on the medullar tissue, the clinical implications of this effect or its relevancy in long-term epidural or intrathecal treatments. For this reasons in this study will be evaluated the possible neurotoxic effects of epidural or intrathecal administration of preservative free ketamine during seven consecutive days, its correlation with the clinical and neurological status and the potential reversibility of the injuries to the neural tissue in rabbits.
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