An investigation of the possible neurotoxic effects of intrathecal midazolam combined with fentanyl in the rat

In previous work, midazolam was injected intrathecally and produced reversible, segmental, spinally mediated anti-nociception sufficient for abdominal surgery in a rat model. The neurotoxic effect of midazolam, alone or combined with fentanyl, injected intrathecally repeatedly on 15 occasions over a period of 1 month, was studied in the same model. We sought to establish whether this would produce neurological damage or neurotoxic injury. Histopathological examination of the excised spinal cord and paraspinal tissues was carried out. Thirty Wistar strain rats with nylon catheters chronically implanted in the lumbar subarachnoid space were divided into five groups: group 1 (n = 6) received 40 mu L of midazolam 0.1%; group 2 (n = 6) received 40 mu L of fentanyl 0.005%; group 3 (n = 6) received 20 mu L of midazolam 0.1% plus 20 mu L of fentanyl 0.005%; group 4 (n = 6) received 40 mu L of lignocaine 2%; group 5(n = 6) received 40 mu L of phenol in water. all substances were injected through the implanted catheters. The neurological recovery of all the animals in the four groups that received intrathecal midazolam alone, fentanyl alone, midazolam plus fentanyl and lignocaine alone was similar and complete. There were no significant differences in the histological changes in the neural tissues of these groups, despite repeated application of the test substances. Group 5 demonstrated the typical neurolytic lesions of phenol when injected intentionally into the subarachnoid space.