Chronic subarachnoid midazolam (Dormicum) in the rat. Morphologic evidence of spinal cord neurotoxicity.

Abstract In humans, the benzodiazepine midazolam has been reported to exert an antinociceptive action after subarachnoid injections. It has been shown that subarachnoid midazolam given to rabbits produces significant pathology in spinal cord morphology, as detected with light microscopy. In order to further characterize these changes, this study was performed, using a more sensitive histologic technique, including electron microscopy as well as unbiased morphometry. The histopathology of the rat lumbar spinal cord was investigated after chronic subarachnoid administration of a commercially available preparation of midazolam. After daily injections of 100 micrograms of midazolam, the animals were transcardially perfused on the twentieth day with a mixture of formaldehyde and glutaraldehyde. Morphometric evaluation of cell number and mean cell volume (MCV) by the disector method revealed a significant lower (P