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

Publication ,  Journal Article
Mogil, JS; Ritchie, J; Smith, SB; Strasburg, K; Kaplan, L; Wallace, MR; Romberg, RR; Bijl, H; Sarton, EY; Fillingim, RB; Dahan, A
Published in: J Med Genet
July 2005

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.

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Published In

J Med Genet

DOI

EISSN

1468-6244

Publication Date

July 2005

Volume

42

Issue

7

Start / End Page

583 / 587

Location

England

Related Subject Headings

  • Reference Values
  • Receptors, Opioid, mu
  • Receptor, Melanocortin, Type 1
  • Pain Threshold
  • Pain Measurement
  • Pain
  • Morphine Derivatives
  • Morphine
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
 

Citation

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Mogil, J. S., Ritchie, J., Smith, S. B., Strasburg, K., Kaplan, L., Wallace, M. R., … Dahan, A. (2005). Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet, 42(7), 583–587. https://doi.org/10.1136/jmg.2004.027698
Mogil, J. S., J. Ritchie, S. B. Smith, K. Strasburg, L. Kaplan, M. R. Wallace, R. R. Romberg, et al. “Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans.J Med Genet 42, no. 7 (July 2005): 583–87. https://doi.org/10.1136/jmg.2004.027698.
Mogil JS, Ritchie J, Smith SB, Strasburg K, Kaplan L, Wallace MR, et al. Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet. 2005 Jul;42(7):583–7.
Mogil, J. S., et al. “Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans.J Med Genet, vol. 42, no. 7, July 2005, pp. 583–87. Pubmed, doi:10.1136/jmg.2004.027698.
Mogil JS, Ritchie J, Smith SB, Strasburg K, Kaplan L, Wallace MR, Romberg RR, Bijl H, Sarton EY, Fillingim RB, Dahan A. Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet. 2005 Jul;42(7):583–587.

Published In

J Med Genet

DOI

EISSN

1468-6244

Publication Date

July 2005

Volume

42

Issue

7

Start / End Page

583 / 587

Location

England

Related Subject Headings

  • Reference Values
  • Receptors, Opioid, mu
  • Receptor, Melanocortin, Type 1
  • Pain Threshold
  • Pain Measurement
  • Pain
  • Morphine Derivatives
  • Morphine
  • Mice, Mutant Strains
  • Mice, Inbred C57BL