Abstract:
BACKGROUND:A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on kappa-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant mu-opioid receptor. OBJECTIVE:To characterise sensitivity to pain and mu-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. METHODS:Comparisons of spontaneous mutant C57BL/6-Mc1r(e/e) mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. RESULTS:C57BL/6-Mc1r(e/e) mutant mice and human redheads--both with non-functional MC1Rs--display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the mu-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. CONCLUSIONS:Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Mogil JS,Ritchie J,Smith SB,Strasburg K,Kaplan L,Wallace MR,Romberg RR,Bijl H,Sarton EY,Fillingim RB,Dahan Adoi
10.1136/jmg.2004.027698keywords:
subject
Has Abstractpub_date
2005-07-01 00:00:00pages
583-7issue
7eissn
0022-2593issn
1468-6244pii
42/7/583journal_volume
42pub_type
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