Naloxazone and pain-inhibitory systems: evidence for a collateral inhibition model

The analgesic responses following morphine and cold-water swims (CWS) can be dissociated from each other. Indeed, certain manipulations in rats such as hypophysectomy or D-phenylalanine injections decrease CWS analgesia while increasing morphine analgesia. The present study examined the reciprocal notion, namely whether a manipulation that decreases morphine analgesia would increase CWS analgesia. Naloxazone, an opiate antagonist which selectively inhibits the high affinity binding site in a long-acting manner, was administered intracerebroventricularly and assessed for its effects upon morphine analgesia and CWS analgesia as measured by the jump test. While intracerebroventricular injections of naloxazone reduced morphine analgesia at 0.5 and 24 hr following microinjection, the same 50 μg dose significantly increased CWS analgesia at 0.5 hr after injection, suggesting a mechanism of collateral inhibition between opioid and non-opioid pain-inhibitory systems.