Selective opioid receptor agonists modulate mechanical allodynia in an animal model of neuropathic pain.
This study evaluated the antinociceptive effects of systemically administered selective opioid agonists of mu (DAMGO), delta (BUBU) and kappa (U 69593) receptors on the vocalization threshold to paw pressure in a rat model of peripheral unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. DAMGO (0.5-2 mg/kg), BUBU (1.5-6 mg/kg) and U 69593 (0.75-3 mg/kg) injected intravenously (i.v.) produced a potent long-lasting antinociceptive effect on both hind paws. The effects on the lesioned paw were clearly and statistically more potent than for the non-lesioned paw. The selective antinociceptive effect of 2 mg/kg DAMGO, 3 mg/kg BUBU and 1.5 mg/kg U 69593 were completely prevented by prior administration of the appropriate antagonists: 0.1 mg/kg naloxone, 1 mg/kg naltrindole and 0.4 mg/kg MR 2266. The present data clearly show that an acute i.v. injection of these selective opioid agonists induces potent antinociceptive effects in a rat model of peripheral neuropathy. These data are discussed with regard to the classical view that there is opioid resistance in neuropathic pain.
INSERM (U161), Unité de Recherches de Physiopharmacologie du Système Nerveux, 75014 ParisFrance Division de Pharmacologie Clinique, et Consultation Commune de la Douleur, Hôpital Cantonal Universitaire de Genève, 1211 Geneva 4 Switzerland.
J A
JA
Desmeules
V
V
Kayser
G
G
Guilbaud
D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000627:therapeutic use; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D014828:Vocalization, Animal / Q000187:drug effects
D000700:Analgesics; D044482:Benzeneacetamides; D001575:Benzomorphans; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C062971:tyrosyl-seryl(O-t-butyl)-glycyl-phenylalanyl-leucyl-threonine(O-t-butyl); D009270:Naloxone; C027247:MR 2266; D009271:Naltrexone; C055382:naltrindole; C045444:U 69593