Intracerebroventricular naloxone produces a dose-dependent, monotonic increase in nociceptive threshold in the rat

Abstract

The intrathecal administration of the opiate antagonist naloxone produced a dose-dependent biphasic change in mechanical nociceptive threshold, in the rat hindpaw. Lower doses (50 pg to 500 ng) produced analgesia while higher doses (5 to 50 micrograms) resulted in successively less analgesia. In contrast, the intracerebroventricular administration of naloxone up to a dose of 5 micrograms (i.e. a dose 10,000 times greater than that required to produce a maximal analgesic effect) only produced analgesia. The ability to differentiate between the analgesic and pain-enhancing properties of naloxone by administration at different anatomical sites is compatible with the suggestion that the analgesic and pain-enhancing effects of naloxone are produced by separate mechanisms of action.