Chronic opioid antagonist treatment facilitates nonopioid, stress-induced analgesia

Chronic exposure to opioid antagonists produces increases brain opioid receptors and enhances morphine analgesia. Since opioid antagonists could affect both opioid and nonopioid analgesic systems, the present study evaluated whether chronic opioid antagonist treatment with naltrexone alters the nonopioid analgesia produced by cold-water swims (CWS). Rats were implanted (SC) with two, 30 mg naltrexone pellets. The pellets were removed 8 days later or left in place and rats tested 24 hr later for analgesia (tail-flick) following a 3.5 min CWS or morphine (3 mg/kg, SC). As expected, morphine analgesia was potentiated in rats with naltrexone pellets removed, but was blocked in rats tested with the naltrexone still implanted. In contrast, naltrexone pretreatment potentiated CWS analgesia, irrespective of whether the pellets were removed or left in place. These findings confirm the nonopioid nature of CWS analgesia and indicate that chronic treatment with an opioid antagonist can affect both opioid and nonopioid analgesic mechanisms.