The role of central mu opioid receptors
in opioid-induced itch in primates

by
Ko MC, Song MS, Edwards T, Lee H, Naughton NN.
University of Michigan.
Pharmacol Exp Ther. 2004 Mar 25


ABSTRACT

Pruritus (itch sensation) is a significant clinical problem. The aim of this study was to elucidate the roles of opioid receptor types and the site of action in opioid-induced itch in monkeys. Observers who were blind to the conditions counted scratching after administration of various drugs. Intravenous (i.v.) administration of mu opioid receptor (MOR) agonists (fentanyl, alfentanil, remifentanil, and morphine) evoked scratching in a dose- and time-dependent manner. 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) evoked scratching, but i.v. DAMGO (0.01-1 mg/kg) did not increase scratching. A similar difference between i.t. and i.v. effectiveness was seen with morphine. Antagonist studies revealed that i.v. administration of an opioid receptor antagonist (naltrexone, 0.0032-0.1 mg/kg) dose-dependently attenuated scratching induced by i.v. fentanyl (0.018 mg/kg) or morphine (1 mg/kg). However, a peripherally selective opioid antagonist (quaternary naltrexone, 0.0032-0.32 mg/kg) did not block i.v. fentanyl- or morphine-induced scratching. Moreover, a histamine antagonist (diphenhydramine, 0.1-10 mg/kg), failed to attenuate scratching induced by i.t. morphine (0.032 mg) or i.v. morphine (1 mg/kg). Pretreatment with a selective MOR antagonist (clocinnamox, 0.1 mg/kg), but not kappa or delta opioid antagonists (nor-binaltorphimine or naltrindole), blocked 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.
Itch
Pain
LAAM
Heroin
Arousal
Morphine
Tramadol
Histamine
Nociceptin
Methadone
Endomorphins
P-glycoprotein
Novelty and pain
Methylnaltrexone
Alvimopan for OBD
Opioid bowel dysfunction
Methylnaltrexone for OBD
Opioids, mood and cognition
Topical opioid antagonist for itching


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