An experimental itch model in monkeys: Characterization of intrathecal morphine-induced scratching and antinociception

Background: The most common side effect of spinal opioid administration is pruritus, which has been treated with a variety of agents with variable success. Currently, there are few animal models developed to study this side effect. The aim of this study was to establish a nonhuman primate model to pharmacologically characterize the effects of intrathecal administration of morphine. Methods: Eight adult rhesus monkeys were used, Scratching responses were videotaped and counted by observers who were blinded to experimental conditions. Antinociception was measured by a warm-water (50 degrees C) tail-withdrawal assay. The dose-response of intrathecal morphine (1-320 mu g) for both scratching and antinociception in all subjects was established. An opioid antagonist, nalmefene, was administered either intravenously or subcutaneously to assess its efficacy against intrathecal morphine. Results: Intrathecal morphine (1-32 mu g) increased scratching in a dose-dependent manner. Higher doses of intrathecal morphine (10-100 mu g) produced thermal antinociception in a dose-dependent manner. On the other hand, nalmefene (10-32 mu g/kg intravenously) attenuated maximum scratching responses among subjects. Pretreatment with nalmefene (32 mu g/kg subcutaneously) produced approximately 10-fold rightward shifts of intrathecal morphine dose-response curves for both behavioral effects. Conclusions: These data indicate that intrathecal morphine-induced scratching and antinociception are mediated by opioid receptors. The magnitude of nalmefene antagonism of intrathecal morphine is consistent with mu opioid receptor mediation. This experimental itch model is useful for evaluating different agents that may suppress scratching without interfering with antinociception. It may also facilitate the clarification of mechanisms underlying these phenomena.