Peripheral component in the enhanced antinociceptive effect of systemic U-69,593, a kappa-opioid receptor agonist in mononeuropathic rats.
The contribution of a peripheral action of the kappa-opioid receptor agonist U-69,593 (trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl) cycloexil] benzene-acetamide methanesulfonate) in the augmented antinociceptive effect of this substance was investigated in a well-established rat model of peripheral unilateral neuropathy (chronic constriction of the common sciatic nerve). Relatively low dose of systemic U-69,593 (0.75 mg/kg intravenous (i.v.)) and intraplantar (i.pl.) low doses of specific antagonists of kappa-(nor-binaltorphimine) or mu-(D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: CTOP) opioid receptors were used. Vocalization thresholds to paw pressure were used as a nociceptive test. The i.pl. injection of nor-binaltorphimine (10-15 microg injected into the nerve-injured hind paw) had no effect on the antinociceptive effect of U-69,593. Higher doses (20-30 microg i.pl. nor-binaltorphimine) significantly reduced the effect of U-69,593 on this paw but not on the contralateral paw, an effect which plateaued at 30 microg. By contrast, the i.pl. injection of CTOP (1 microg into the nerve-injured paw) had no effect on U-69,593 antinociception, whereas it reduced the effect of systemic morphine in these animals. The doses of nor-binaltorphimine used, injected into the contralateral paw or i.v., failed to modify the antinociceptive effects of U-69,593 on either paw. These results provide evidence for a peripheral component in the enhanced antinociceptive effect of systemic U-69,593 in this model of neuropathic pain.
Catheline
G
G
Unité de Recherches de Physiopharmacologie du Système Nerveux, I.N.S.E.R.M. U 161, Paris, France.
Guilbaud
G
G
Kayser
V
V
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides; D007275:Injections, Intravenous; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009408:Nerve Compression Syndromes / Q000188:drug therapy*; D010147:Pain Measurement; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012584:Sciatic Nerve; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D000700:Analgesics; D044482:Benzeneacetamides; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; C045444:U 69593