Subarachnoid midazolam: histologic study in rats and report of its effect on chronic pain in humans

Subarachnoid administration via a catheter of a water-soluble benzodiazepine, midazolam, was tested in the control of cancer pain. First, the lack of its toxicity during constant subarachnoid administration (50 micrograms per day) was assessed in the rat. After 15 days of treatment, a histologic examination of the spinal cord revealed the same amount of fibrosis, infiltration, and deformation in the control group (n = 14), which had received only saline, as in the test group (n = 18), treated with subarachnoid midazolam. Therefore, the histologic changes observed in the spinal cord probably are related to the presence of the catheter. After these results, a mixture of 2 mg midazolam and a variable dose of subarachnoid morphine was injected in two patients presenting chronic neoplastic pain resistant to high doses of morphine. In these two cases, the addition of midazolam appeared to be effective in controlling intractable neoplastic pain.