Is there genetic polymorphism evidence for individual human sensitivity to opiates?
Opiate analgesics have been widely used for severe acute pain and chronic cancer-related pain. Individual differences in the effectiveness of opiates and their side effects limit the clinical benefits and increase risks of drug abuse. Genetic factors might affect variations of opiate sensitivity. The mu opioid peptide receptor (MOP) is the principal site of pharmacologic actions for most clinically important opiate drugs. Recent studies using various knockout mice and recombinant-inbred strain CXBK mice have indicated that the analgesic effect of morphine is dependent on the amount of the MOP. There are more than 100 polymorphisms identified in the human MOP (OPRM1) gene. These polymorphisms might be correlated with OPRM1 mRNA stability and opiate sensitivity, including opiate analgesia, tolerance, and dependence. More precise studies on the relationship between gene polymorphisms and opiate sensitivity will enable realization of personalized pain treatment by predicting opiate sensitivity and requirement for each patient.
Nagashima
Makoto
M
Department of Molecular Psychiatry, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Katoh
Ryoji
R
Sato
Yasuo
Y
Tagami
Megumi
M
Kasai
Shinya
S
Ikeda
Kazutaka
K
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D051379:Mice; D018847:Opioid Peptides / Q000235:genetics; D010146:Pain / Q000188:drug therapy* / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu