Chronic selective blockade of mu opioid receptors produces analgesia and augmentation of the effects of a kappa agonist.

We have previously demonstrated that, when administered chronically, naloxone and naltrexone have the paradoxical effect of producing analgesia in rats. In this study, rats treated chronically with intracerebroventricular (i.c.v.) microinjections, and mice treated chronically with subcutaneous (s.c.) injections of naloxone or beta-funaltrexamine (beta-FNA) developed analgesia on daily hot plate tests. There was not drug effect on the first day of hot plate testing, but significant increases in paw lick latency developed over subsequent acquisition sessions for animals treated with beta-FNA or naloxone. An augmented analgesic response to a 5 mg/kg s.c. injection of the kappa opioid agonist, U50-488H, was observed in mice previously treated with naloxone or beta-FNA. The primary findings of the present study were: (1) chronic blockade of mu opioid receptors is sufficient to produce analgesia on repeated hot plate tests in both rats and mice; (2) chronic blockade of mu receptors in the presence of stressful stimuli results in augmentation of kappa agonist-induced analgesia; and (3) the phenomenon of opioid blockade-induced analgesia (OBA) occurs in mice as well as rats.