title: "Paradoxical" analgesia induced by naloxone and naltrexone.
abstract: Analgesic effects of pellet implantation of the opiate antagonists naloxone and naltrexone and of chronic administration of naloxone by subcutaneous injection were examined. Rats were implanted with a slow-release pellet containing 10 mg naloxone or 10 mg naltrexone and tested for paw-lick latency on a hotplate apparatus. Controls were implanted with placebo pellets or given saline injections as appropriate. There were five test trials at intervals up to 72 h after implantation of naloxone and up to 120 h after the implantation of naltrexone. In a separate experiment, 5 mg/kg naloxone was injected; there were single trials on 5 consecutive days. All drug-treated animals displayed clear and substantial analgesia by their second test trial. This "paradoxical" analgesia was gradually reversed in the pellet-implant groups as tissue levels of the antagonists declined, but increased progressively with each trial involving injections. It was hypothesized that blockade of endogenous opiates by antagonists resulted in a form of "super-pain" on the hotplate, which in turn activated a normally redundant "backup" analgesic system. The results with naloxone injections show that unlike opiate-mediated analgesia, this hypothetical system is resistant to tolerance.
authors.affiliation: Addiction Research Foundation, Toronto, Ontario, Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Greeley
authors.forename: A D
authors.initials: AD
authors.lastname: Lê
authors.forename: C X
authors.initials: CX
authors.lastname: Poulos
authors.forename: H
authors.initials: H
authors.lastname: Cappell
mesh_terms: D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003692:Delayed-Action Preparations; D007279:Injections, Subcutaneous; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D009270:Naloxone; D009271:Naltrexone