“While we believe pain is the same in all women of all hair colours,” explained Mogil, “our study shows women with red hair respond better to the pain-killing drug we tested than anyone else -- including men.”
Previous research suggested the existence of a female-specific pain pathway in the brain. Analgesics that target receptors in this pathway, called kappa-opioid receptors, have been reported to work only in women. Using a technique called quantitative trait locus mapping, Mogil and his colleagues identified a candidate gene that may be responsible for this sex difference. Interestingly, the gene, called Mc1r, was first associated, not with neurological function, but with pigmentation. Variants of the gene cause red hair and fair skin in humans.
Redheads and painkillers
The scientists tested the effects of the kappa -specific analgesic on mutant mice with an inactive variation of Mc1r analogous to the "redhead" variation in humans. Although typical sex differences in analgesic effects were seen in normal mice, these differences disappeared in the mutants. The researchers then tested a clinically used kappa analgesic, pentazocine, on male and female humans with several Mc1r variations causing different hair colors and skin types. The Mc1r variations did not affect analgesic response to pentazocine in men, but caused a heightened response in redheaded, fair-skinned women. These results suggest that Mc1r modulates a kappa-specific pain pathway only in females.
Authors: "The Melanocortin-1 Receptor Gene Mediates Female-Specific Mechanisms of Analgesia in Mice and Humans," by Jeffrey S. Mogil, Sonya G. Wilson, Elissa J. Chesler, Andrew L. Rankin, Kumar V. S. Nemmani, William R. Lariviere, M. Kristina Groce, Margaret R. Wallace, Lee Kaplan, Roland Staud, Timothy J. Ness, Toni L. Glover, Magda Stankova, Alexander Mayorov, Victor J. Hruby, Judith E. Grisel and Roger B. Fillingim.
Jeffrey Mogil , the E.P. Taylor Professor of Pain Studies at McGill, is a repatriated Canadian who was recruited from the University of Illinois at Urbana-Champaign, where he first identified sex-specific genetic circuitry that governs the way males and females respond to pain. More generally, Mogil has been examining the genetic and environmental influences that combine to govern reactions to pain. At a minimum, pinpointing relevant genes can help doctors tailor dosages of drugs to each patient’s needs. At best, Mogil’s work may lead to new drugs providing life-saving pain relief.
About McGill University:
Located in Montreal, QC, Canada, McGill has earned an international reputation for scholarly achievement and scientific discovery. Founded in 1821, McGill is one of two Canadian members of the American Association of Universities, which it joined in 1925. McGill’s 22 faculties and professional schools offer more than 300 programs, from the undergraduate to the doctoral level. The University’s professors have earned graduate degrees and completed their training in leading academics centres around the world. In 2000-2001, McGill led all Canadian universities in terms of research funding per full-time faculty member and its scholars published more frequently than any other Canadian university. McGill attracts top students from over 150 countries, creating one of the most dynamic and diverse student bodies in North America. The University has approximately 22,711 undergraduate students and 6,362 graduate students.
Proceedings of the National Academy of Sciences