"Paradoxical" analgesia induced by naloxone and naltrexone

Janet D. Greeley, A. D. Lê, Constantine X. Poulos, Howard Cappell*

*Corresponding author for this work

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)36-39
Number of pages4
JournalPsychopharmacology
Volume96
Issue number1
DOIs
Publication statusPublished - Sep 1988

Keywords

  • Analgesia
  • Naloxone
  • Naltrexone
  • Opiates
  • Pain

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