TY - JOUR T1 - Melanocortin-1 receptor gene variants affect pain and μ-opioid analgesia in mice and humans JF - Journal of Medical Genetics JO - J Med Genet SP - 583 LP - 587 DO - 10.1136/jmg.2004.027698 VL - 42 IS - 7 AU - J S Mogil AU - J Ritchie AU - S B Smith AU - K Strasburg AU - L Kaplan AU - M R Wallace AU - R R Romberg AU - H Bijl AU - E Y Sarton AU - R B Fillingim AU - A Dahan Y1 - 2005/07/01 UR - http://jmg.bmj.com/content/42/7/583.abstract N2 - Background: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on κ-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 μ-opioid receptor. Objective: To characterise sensitivity to pain and μ-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. Methods: Comparisons of spontaneous mutant C57BL/6-Mc1re/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-Mc1re/e mutant mice and human redheads—both with non-functional MC1Rs—display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the μ-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. ER -