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-, del ta- and kappa-agonists, DAMGO (2 and 3 mg/kg), BUBUC (3 and 6 mg/kg) a nd U-69,593 (1.5 mg/kg), were evaluated by measuring the struggle late ncy (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 degree s C) water bath. Experiments were performed 2 weeks after surgery. The agonists were used at doses that produced potent antinociceptive effe cts on the vocalization test in this model. At 46 degrees C (clearly i n 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 ma ximum 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 relie ve the abnormal reactions to 10 degrees C, 42 degrees C (in the non-no xious 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 o f mononeuropathic pain. This may be due to the activation of different types of fibers and/or to the progressive increase in the number of a ctivated fibers in response to different intensities of stimuli and co uld partly explain differences in the efficacy of opioids in neuropath ic pain syndromes in clinical practice.