| First Author | Mogil JS | Year | 2005 |
| Journal | J Med Genet | Volume | 42 |
| Issue | 7 | Pages | 583-7 |
| PubMed ID | 15994880 | Mgi Jnum | J:112815 |
| Mgi Id | MGI:3663586 | Doi | 10.1136/jmg.2004.027698 |
| Citation | Mogil JS, et al. (2005) Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet 42(7):583-7 |
| abstractText | 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. |
