[The antinociceptive effects of fentanyl, midazolam and clonidine and their interactions in the spinal dorsal horn]

Abstract

Lamina V-type neurons on the spinal dorsal horn which responded to the bradykinin injection into the femoral artery were studied neurophysiologically in the spinal transected cats by the tungsten microelectrode method. It has been demonstrated that the separate and combined antinociceptive effects of fentanyl, clonidine and midazolam administered intrathecally can produce reduction in response to noxious stimuli. Fentanyl (25 micrograms), clonidine (30 micrograms) and midazolam (1.0 mg) separately suppressed noxious evoked activity at the spinal level. On the other hand, fentanyl (5 micrograms), clonidine (5 micrograms) and midazolam (0.5 mg) each produced no significant suppression of the evoked activity. However, the combinations of drugs at lower doses produced supra-additive suppressive effect. These suppressive effects were reversed by each antagonist (naloxone, yohimbine and flumazenil). These findings suggest that when two of these drugs are combined at subanalgesic doses, a significant synergistic interaction is exerted. Therefore, the use of these drugs in combination can reduce the total amount of any one drug required for analgesia in the spinal cord and also reduce the side effects of these agents.