The influence of sustained opioid receptor blockade in a model of long-term, localized inflammatory pain in rats.
Rats were subcutaneously implanted with minipumps delivering naloxone (3.0 mg/kg/h) or distilled water. One day later, they were inoculated in the plantar surface of the right hind paw with Mycobacterium butyricum. Naloxone blocked the antinociceptive action of the mu-agonist, morphine, and the kappa-agonist, U69,593, and led to a sustained reduction in food and water intake. Thus, opioid receptors were effectively occupied. Rats receiving naloxone showed significantly less hindlimb swelling on days 2 and 3 post-implantation. On day 2 but not 5 post-implantation, the hyperalgesic response of the inoculated paw to noxious pressure was potentiated in rats receiving naloxone. At six days post-implantation, pumps were removed. Ten days after removal, the inflammation and hyperalgesia had spread to the contralateral hindlimb and to the forelimbs. The degree of this transfer was less pronounced in rats which had been receiving naloxone. These data suggest that opioids, via kappa-receptors, play a role in the control of nociception under inflammatory pain: however, this role may not be indispensable. Further, the processes governing the development and spread of inflammatory disease may be modulated by opioid mechanisms.
Millan
M J
MJ
Neurobiology Division, FONDAX-Groupe de Recherche SERVIER, Puteaux, France.
Colpaert
F C
FC
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides; D004327:Drinking Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D007249:Inflammation / Q000150:complications*; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D011759:Pyrrolidines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D000700:Analgesics; D044482:Benzeneacetamides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; C045444:U 69593