FURTHER EVIDENCE FOR A PERIPHERAL COMPONENT IN THE ENHANCED ANTINOCICEPTIVE EFFECT OF SYSTEMIC MORPHINE IN MONONEUROPATHIC RATS - INVOLVEMENT OF KAPPA-OPIOID, BUT NOT DELTA-OPIOID RECEPTORS

The contribution of a peripheral action of morphine in the augmented a ntinociceptive effect of this substance was re-evaluated in a well est ablished rat model of peripheral unilateral mononeuropathy (chronic co nstriction Of the common sciatic nerve), using a relatively low dose o f systemic morphine (1 mg/kg i.v.) and local low doses of specific ant agonists of kappa- (nor-binaltorphimine) or delta-(naltrindole) opioid receptors. Vocalization thresholds to paw pressure were used as a noc iceptive test. Escalating doses of nor-binaltorphimine (10-30 mu g inj ected locally into the nerve injured paw) significantly and dose depen dently reduced the effect of morphine on this paw but not on the contr alateral paw, an effect which plateaued at 30 mu g. By contrast, the l ocal injection of naltrindole (30-40 mu g into the nerve injured paw) had no effect on morphine analgesia. The doses of opioid receptor anta gonists used, injected i.v., in the contralateral paw, or alone in the nerve injured paw had no significant effect. These results suggest th at the peripheral effect of systemic morphine in this model of neuropa thic pain could be mediated not only by mu- but also by kappa-opioid r eceptors.