Redheads and painkillers

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McGill Reporter
April 3, 2003 - Volume 35 Number 13
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Home > McGill Reporter > Volume 35: 2002-2003 > April 3, 2003 > Redheads and painkillers

Redheads and painkillers

Redheads often get a bad rap: Anne of Green Gables was a troublemaking orphan with a fiery temper, while Lilith was Adam's sinful first wife with a thing for demons. Well, it turns out scarlet women have at least one advantage over their blonde and brunette sisters.

Psychology professor Jeffrey Mogil has proved that a gene that causes red hair and fair skin also plays a role in how some women respond to painkillers.

Psychology professor Jeffrey Mogil
Photo: Owen Egan

"In a nutshell, what we found is red-headed women are more sensitive to the effects of a particular class of analgesics. It's called pentazocine, [a type of] analgesic called kappa-opioids," explained Mogil.

Although not commonly prescribed, these drugs are sometimes used in dealing with labour pains. Mogil explained that the drugs are not often given to patients because, in part, they're not thought to work all that well for most people.

Pentazocine is more effective on the crimson-crowned due to a variant of the gene melanocortin-1 (Mc1r). Though the gene is found in everyone, one variant of Mc1r is responsible for the distinctive pigmentation of 65 percent of all redheads (unrelated genes are the cause for the remaining 35 percent). The more common variant found in blondes and brunettes produces a protein that normally blocks the effect of kappa-opioid drugs. In redheads that protein isn't doing its job, and so pentazocine can work unhindered.

"The fact that this gene plays a role in hair colour and in analgesia is completely random, we think. It's not that pain has anything to do with hair colour. It's just that this gene produces protein, and this protein is in the skin where it does one thing, and in the brain it does something else," said Mogil.

The correlation might be random, but how it was discovered was not. Mogil had already found a gene near the end of mouse chromosome 8 that appeared to affect pain inhibition in female -- but not male -- mice.

"In this most recent study, we figured out which gene it was, and we used mutant mice lacking the melanocortin-1 gene. They're essentially the mouse equivalent of redheads."

Rose-tinted rodents worried about freckling in the sun these were not: "redhead" mice actually are beige in tone. Mogil found that the mutant females responded best to the analgesic, compared to the equivalent males or the 'normal' control mice.

"That's all well and good for the mice, but does this have anything to do with people?" was his next question. He recruited a collaborator in the U.S. to find out. Locating subjects was pretty easy, although checking whether they were in fact the kind of "real" redheads they were looking for was a little more complicated than comparing their eyebrows to their bangs.

"It wasn't enough to look at the hair colour and the skin colour. We actually had to sequence that gene and find out what their status was," explained Mogil.

The results for humans were similar to mice, but why? Mc1r causes red hair in men and women, so one would expect that the analgesic effects would be the same. Not so, said Mogil. Men and women process pain differently, and that is the crux of the study.

"The neural circuits that are responsible for pain inhibition are different in males and females. The female pathway simply contains a melanocortin-1 receptor somewhere in it, and the male circuit doesn't," he said. His next step will be to find out where in the neural circuit those receptors are.

It's unlikely that pentazocine will become the de rigueur painkiller for carrot-tops worldwide: the side-effects of the drug remain, and better painkillers are out there. So why does this study matter?

"We've shown that just like in mice, men and women have separate pathways for pain. If they have separate pathways, one could imagine that if you could figure out what was going on in these pathways you could develop separate drugs. It might be useful because women have a higher prevalence of any number of chronic pain disorders, like fibromyalgia and migraines."

Moreover, Mogil's work is on the forefront of a brave new world in medical research.

"This is a pretty good example of pharmacogenetics, which is something that's causing quite a bit of excitement right now. It's the idea that treatment decisions -- the dose and type of drug -- might be based on genetic status. If you know what genes are relevant to drug responses you can test people beforehand and predict how well they're going to respond and decide whether to use it or not."

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