Differential action of morphine and various opioid agonists on thermal allodynia and hyperalgesia in mononeuropathic rats.
In a rat model of mononeuropathy produced by 4 loose ligatures around the common sciatic nerve, the effects of 1 mg/kg morphine and mu-, delta- and kappa-agonists, DAMGO (2 and 3 mg/kg), BUBUC (3 and 6 mg/kg) and U-69,593 (1.5 mg/kg), were evaluated by measuring the struggle latency (SL in sec) to immersion of the paw on the nerve-injured side in a cold (10 degrees C) or hot (42 degrees C, 44 degrees C, and 46 degrees C) water bath. Experiments were performed 2 weeks after surgery. The agonists were used at doses that produced potent antinociceptive effects on the vocalization test in this model. At 46 degrees C (clearly in the noxious range), only morphine and DAMGO had significant effects. The effect of morphine lasted for more than 2 h with a maximum at 40 min (SL = 13.8 +/- 1.6 sec, 252% of control values). For 2 and 3 mg/kg DAMGO, the dose-related effect lasted for 120 min at least, with a maximum at 20-40 min (SL = 6.0 +/- 0.5 and 8.8 +/- 0.7 sec, 148% and 170% of control values, respectively). These effects were more potent and prolonged than in normal rats and were reversed by 0.1 mg/kg naloxone i.v. By contrast, morphine and all selective agonists failed to relieve the abnormal reactions to 10 degrees C, 42 degrees C (in the non-noxious range) and 44 degrees C (at the noxious threshold) stimuli. Our data illustrate a differential effect of opioids on nociceptive tests based on different stimulus modalities and intensities in this model of mononeuropathic pain.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
S H
SH
Unité de Recherches de Physiopharmacologie du Système Nerveux, Inserm U 161, 2 rue d'Alesia, 75014, ParisFrance.
Kayser
V
V
Desmeules
J
J
Guilbaud
G
G
D000818:Animals; D003080:Cold Temperature; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D012584:Sciatic Nerve / Q000187:drug effects
D011957:Receptors, Opioid; D009020:Morphine