Effects of midazolam in the spinal nerve ligation model of neuropathic pain in rats

Potential changes in the spinal GABAergic activity after nerve injury were studied by comparing the effects of systemic administration of the benzodia zepine midazolam on the noxious evoked responses of dorsal horn in rats wit h spinal nerve ligation of neuropathy and control animals. The tight ligati on of the L-5 and L6 spinal nerves was performed in adult male Sprague-Dawl ey rats and resulting mechanical and cold allodynia were assessed with von Prey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15-18 days after the surgery under h alothane anaesthesia using transcutaneous electrical stimulation of the rec eptive field at three times the C-fibre threshold. The rats in the spinal n erve ligation group, but not in the sham-operated control group developed m echanical and cold allodynia. Subcutaneous administration of midazolam 0.1- 3.0 mg/kg reduced the A delta-fibre evoked activity in a dose-related manne r in all study groups, but the C-fibre evoked activity was significantly re duced only in the spinal nerve ligation group. The inhibitory effects of s. c. midazolam were significantly reversed by i.t. administration of flumazen il, suggesting a spinal site of action. Midazolam reduced C-fibre evoked fi ring significantly more in the spinal nerve ligation model than in the non- operated or sham controls. These results indicate changes in the spinal GAB Aergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All r ights reserved.