Role of central versus peripheral opioid receptors in analgesia induced by repeated administration of opioid antagonists.
Although analgesia induced by blockade of opioid receptors has been well established, it is still unknown whether its development is mediated by the blockade of centrally located opioid receptors. Therefore, rats were treated with either systemically or ICV applied naloxone or quaternary naltrexone (QN), an opioid antagonist that does not easily penetrate the blood-brain barrier. Following antagonist administration, each animal was tested for paw lick latency on a 51 degrees C hot plate. Hot plate testing and drug injections were carried out for 4 consecutive days. Rats treated with ICV microinjections of QN or naloxone displayed paw lick latencies that were significantly longer than those observed in control animals. In contrast, rats treated with SC injections of QN did not show any increase in paw lick latency, whereas rats treated with SC injections of naloxone displayed paw lick latencies that were significantly longer than those of control rats. These results are consistent with the hypothesis that the blockade of central opioid receptors underlies the development of an analgesic response.
Walker
M J
MJ
Addiction Research Foundation, Toronto, Ontario, Canada.
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Poulos
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Cappell
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D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D011957:Receptors, Opioid; C032257:methylnaltrexone; D009271:Naltrexone