Human genetics: Redhead receptor 5/8/05. By Ian Jones People have red hair because they possess a variant melanocortin-1 receptor gene. This also affects their sensitivity to pain and pain relief.

The melanocortin-1 receptor affects pigmentation across the animal world, from human hair colour to bird plumage. Interestingly, though, it also has an influence on other aspects of physiology – including pain responses.

Jeffrey Mogil and colleagues at McGill University in Montreal, Canada, recently discovered that some variants of the MC1R gene make people and mice more sensitive to pain and to pain relief mediated through the kappa-opioid receptor in the brain.

Clinically, though, pain relief mediated through the mu-opioid receptor is more important. Now, the McGill team has found that mice lacking a functional MC1R gene, as well as human redheads, are also less sensitive to painful stimuli and more responsive to a morphine-like compound that acts through the mu-opioid receptor.

The redhead variants of MC1R have been thought to be non-functional versions of the receptor. However, Kimberley Beaumont and colleagues in Brisbane have found that they may still be active, but coding changes in the MC1R gene prevent the receptor being transported to the surface of the cell.

Further reading

Mogil JS et al. Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet 2005;42(7):583–7. Abstract

Beaumont KA et al. Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Hum Mol Genet 2005;14(15):2145–54. Abstract