Evidence for separate involvement of different mu-opioid receptor subtypes in itch and analgesia induced by supraspinal action of opioids.
The common adverse effect of centrally-injected mu-opioid receptor (mu-OR) agonists is pruritus. This study was conducted using mice to examine whether different subtypes of mu-OR would be responsible for pruritus and analgesia. Intracisternal injections of morphine and morphine-6beta-glucronide (M6G), but not M3G, produced an antinociceptive effect. Morphine, but neither M6G nor M3G, induced facial scratching, a pruritus-related response. Facial scratching following morphine was not affected by the mu(1)-OR antagonist naloxonazine at doses that inhibited the antinociceptive effects. The results suggest that different subtype and/or splice variants of mu-OR are separately involved in pruritus and antinociception of opioids.
Andoh
Tsugunobu
T
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan.
Yageta
Yuichi
Y
Konno
Mitsuhiro
M
Yamaguchi-Miyamoto
Tomomi
T
Takahata
Hiroki
H
Nojima
Hiroshi
H
Nemoto
Hideo
H
Kuraishi
Yasushi
Y
D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage* / Q000633:toxicity; D009022:Morphine Derivatives / Q000008:administration & dosage; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000008:administration & dosage; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011537:Pruritus / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D013997:Time Factors
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; C404943:Oprm protein, mouse; D017450:Receptors, Opioid, mu; D009270:Naloxone; C035349:morphine-6-glucuronide; D009020:Morphine; C034643:naloxonazine; C018108:morphine-3-glucuronide