Do redheads really feel more pain? The jury’s still out

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You may have seen the recent (and well-publicized) study that shows redheads are more scared of the dentist than other people are. The idea is that the same gene variant that leads to red hair also — for some reason — makes people more susceptible to pain, and less receptive to the common anesthetics that a dentist might use before pulling out a drill. The end result: Redheads dread their excruciating dental work, while others just get numb cheeks — a minor inconvenience.

Actually, the science that links red hair to pain susceptibility has been around for several years. But is it really true that redheads feel more pain? The evidence is surprisingly murky. In fact, some studies suggest exactly the opposite result, that redheads have a higher pain threshold because of their variant of exactly the same gene, the melanocortin 1 receptor gene, or MC1R gene.

This latest finding about redheads at the dentist comes from a group of researchers that includes Daniel Sessler, who also worked on the link between red hair and the effectiveness of anesthetics. His research firmly suggests that redheads do feel more pain: Not only do they have lower response to anesthetics, redheads also show a more acute response to pain from heat, the study results show. But a separate group of researchers at McGill University have tested mice and humans only to find that those with the gene variant have higher pain tolerance, reacting less strongly to pain. Those scientists also found a heightened sensitivity to painkillers among the redheads.

I talked to the author of some of that contrary research, McGill neuroscientist Jeffrey Mogil, about the apparent contradiction, and the link between hair color and pain.

[The following has been edited for length.]

TIME: Why did you want to examine the relationship between hair color and pain in the first place?

JM: It’s interesting. We and the Sessler group came at this question from completely different angles. Sessler was investigating lore among anesthesiologists, seeing if it was really true [that redheads feel more pain]. We weren’t interested in redheads at all. We’re a lab that does gene mapping in mice, and we were interested in a particular kind of analgesia. We went through a long, laborious process of trying to finding which gene was responsible for differences among strains — and that gene just turned out to be the melanocortin 1 receptor gene, which is also the redhead gene.

TIME: I’m not quite clear. This gene: Is this something that every redhead has, so that every redhead will respond to pain in the same way?

JM: Well everyone has every gene. But redheads inherit certain variants of the gene, and in this particular case, they inherit variants of the gene that make a protein not work. If it’s not working you have red hair instead of the brown hair you [would otherwise] have. The idea here is that wherever else this protein is in the body and the brain – and whatever other function it happens to be involved in – if the protein is not working, you will alter the system accordingly.

It turns out there are melanocortin 1 receptors in the midbrain and they participate in pain and pain inhibition. In our hands, redheads are less sensitive to pain and more sensitive to pain inhibition from analgesic drugs. But of course Sessler, in terms of pain, finds the opposite.

TIME: So there are two groups who’ve worked on this – your group and, you said, the Sessler group in Louisville. They find that people with a particular version of this gene need more anesthetic…

JM: I need to stop you. The anesthetic finding and the analgesic finding are not contradictory. They’re similar words so people confuse them. But sensitivity to anesthesia [which numbs the senses] and sensitivity to analgesia [painkillers] are completely different things. They have nothing to do with each other. There are completely different brain areas and neural circuits that underlie those two things.

The only contradiction is in pain sensitivity, which we’ve both looked at and found opposite results. Their pain sensitivity measure was thermal, and our measure in humans was electric shock, so that might explain it. But I’m not so sure about that because we’ve tested redhead mutant mice on a number of modalities of pain and the mice always come up in the same direction. The mutant mice are less sensitive to pain, just like we find in redhead humans. There’s no simple resolution here unfortunately.

TIME: How would you go about resolving it?

JM: You know, the usual stock answer: More research is needed!

If anyone was interested they could test redheads on a number of different pain modalities. Ideally this would be a third group, neither us nor [the Sessler group].

TIME: OK. How does someone even measure sensitivity to pain?

JM: Heat hurts, so you can test with that. Electric shock hurts. You can test with that. Mechanical pressure hurts. In mice, you largely measure their withdrawal. Up to a threshold, you poke them or you’re heating their paws and they’re fine. They don’t do anything. Then once you exceed a certain threshold they remove themselves from the stimulus. They’ll go away from it. In humans it’s essentially the same thing, except instead of going away from it they just tell you to stop, or they give you a number and if that number goes too high then the experimenter stops. It’s not as different as people pretend.

TIME: Anything else that people should know about the relationship between hair color and pain?

JM: I think there’s two reasons why this line of work is important. No. 1, it shows that genes can have many, many different functions and they don’t have to have anything to do with other. If you think about it, that has to be the case. There are about 20,000 genes, and think how many biological phenomena there are: millions, maybe an infinite number. Genes do many, many things, so it’s not really a surprise that the same gene could have a role to play in [things that seem unrelated, like] hair color and pain.

I think the other important thing is that this shows the power of two very different approaches to science. You can either go top-down as they did, and start with something that medical doctors kind of whisper about, and see whether it’s true. Or you can go bottom-up like we did and start with basic science questions in the mouse and then move up to humans later. I find it interesting that two different groups using completely different techniques could end up studying the same question.

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