Opioid action: Role of central mu opioid receptors in opioid-induced itch in primates

Abstract

Pruritus (itch sensation) is one of side effects associated with opioid analgesics. The aim of this study was to elucidate the role of opioid receptor types and the site of action in opioid-induced itch in monkeys. Scratching responses after administration of various drugs were counted by observers blinded to conditions. Systemic administration of mu opioid receptor (MOR) agonists (morphine, fentanyl, alfentanil, and remifentanil) evoked scratching dose- and time-dependently. However, a kappa opioid agonist (U-50488H) and a delta opioid agonist (SNC80) did not increase scratching. Intrathecal (i.t.) administration of a peptidic MOR agonist (DAMGO, 0.00032-0.01 mg) potently evoked scratching. However, i.v. administration of DAMGO (0.01-1 mg/kg) did not increase scratching. This large potency difference between i.t. and i.v. routes was also observed with morphine-induced scratching (i.t., 0.0032-0.032 mg; i.v., 0.1-3.2 mg/kg). In addition, systemic administration of an opioid receptor antagonist, naltrexone (0.0032-0.1 mg/kg), dose-dependently attenuated i.v. fentanyl (0.018 mg/kg)- or morphine (1 mg/kg)-induced scratching. However, quaternary naltrexone (0.0032-0.32 mg/kg) did not block either i.v.. fentanyl- or morphine-induced scratching. Moreover, systemic administration of naltrexone (0.0032-0.032 mg/kg) dose-dependently attenuated i.t. morphine (0.032 mg)-induced scratching. In contrast, an antihistamine, diphenhydramine (0.1-10 mg/kg), did not attenuate i.t. morphine-induced scratching. Taken together, these data suggest that MOR, not other opioid receptor types or histamine, mediates scratching evoked by opioid analgesics. More important, this study provides in vivo pharmacological evidence that activation of central MOR plays an important role in opioid-induced itch in primates (Supported by USPHS Grant DA13685).