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. This may be due to the activation of different types of fibers and/or to the progressive increase in the number of activated fibers in response to different intensities of stimuli and could partly explain differences in the efficacy of opioids in neuropathic pain syndromes in clinical practice.