Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Mogil, JS; Ritchie, J; Smith, SB; Strasburg, K; Kaplan, L; Wallace, MR; Romberg, RR; Bijl, H; Sarton, EY; Fillingim, RB; Dahan, A

Published Date

  • July 2005

Published In

Volume / Issue

  • 42 / 7

Start / End Page

  • 583 - 587

PubMed ID

  • 15994880

Pubmed Central ID

  • PMC1736101

Electronic International Standard Serial Number (EISSN)

  • 1468-6244

Digital Object Identifier (DOI)

  • 10.1136/jmg.2004.027698


  • eng

Conference Location

  • England