You may have heard that redheads feel less pain.

And you may also have heard that they need more anesthesia to knock them out in surgery. And science says that both  of those things are true!

Which is kinda weird, isn’t it? Like, isn’t that a contradiction? Why do they need more drugs but feel less pain?

And what does hair color  have to do with any of it? Well, it turns out that the  genes that control our hair and skin color are a lot more  multi-purpose than you’d think. So here’s what we know about redheads’  secret pain-sensing superpowers. [♪ INTRO] If you’ve ever stepped on a Lego before,  you know what extreme pain feels like.

But as common as it is, pain is surprisingly  hard for scientists to understand. For one thing, our bodies  have lots of different ways of telling us when and how we’re hurting. We have different nerve endings to  recognize different kinds of pain, like heat versus pressure, and  there are different types of signals that can raise or lower our perception of pain.

But pain is especially hard  to study because doctors can’t measure it objectively the way they  do for something like blood pressure. Instead, they use this very high-tech  tool: a chart of smiley and frowny faces, where you point to the face  that matches how you feel. I don’t think I need to tell you  that that’s highly subjective, which makes it hard to tell how well  a new pain medication is working.

And it’s especially confusing  because individual people have different levels of pain tolerance. You probably know someone  who acts like a total baby every time they bump their funny bone. And then there’s James Bond, who  can get shot and beat up all day and still go on to stop the bad guys.

And sure, he’s fictional. But still. When researchers have tried to look at  some of those variations in how people respond to pain, they noticed a fairly  unexpected group of people who stuck out.

See, as far back as 2005, researchers  noticed that people with red hair tend to respond to pain medications  differently than non-redheads. Studies have found that redheads  need about 20% more anesthesia gas than non-redheads before they stop  responding to a painful electrical stimulus. And the same is true with localized  anesthetics like lidocaine, which is the injectable numbing agent that’s  used during things like dental surgery.

Some studies have even found that  redheads are more likely to be afraid of going to the dentist – possibly because  they’re less likely to get enough anesthetic to keep them from feeling the drilling. Which is fair. I’d be scared too!

But it gets even more confusing, because  while redheads are more sensitive to some types of pain, including heat,  they are less sensitive to others. To scientists, figuring all this  out has been, well, a real pain. And while parts of the story are still a  mystery, researchers have gotten closer to figuring out one part: the weird  relationship between the gene for red hair and an altered  response to opioid medications.

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Now before we get too far into all this, let’s start by talking about  where red hair comes from. Like other parts of the body, hair gets  its color from cells called melanocytes, which produce several different  types of pigments called melanins. The two main types are a dark  brownish pigment called eumelanin and a reddish-yellow pigment called pheomelanin.

People with dark skin generally have more  eumelanin than those with lighter skin, but we all produce pheomelanin in some body parts, like our lips, and some of  your other pinkish bits. The differences between melanin  types are why some people can get a suntan more easily than others. If your cells can make a lot of  eumelanin, your skin can darken when it’s exposed to intense  sunlight, which blocks those UV rays from doing more damage to your DNA.

But if you produce a lot of pheomelanin,  your cells just kinda get stressed out, and that lack of protection  allows your skin to burn. Melanocytes know which pigment to produce because the body sends them  instructions through molecular signals. And they pick up on these  signals using a receptor protein on their surfaces known as MC1R.

You can think of MC1R as a  switch that tells your cells whether to print in red or brown ink. When MC1R is on, the cells  start making more eumelanin. But when MC1R is off, the  cells just make pheomelanin.

Now, redheads have a mutation in their MC1R gene. And lots of red animals like Irish Setters  have that mutation too, although we’re still waiting on the genotyping to find out if  that includes Clifford The Big Red Dog. The mutation makes it more  difficult to activate MC1R, meaning that the cells are  all pheomelanin, all the time.

And so, voila: red melanin, red hair. That mutation also explains why  so many fair-skinned redheads don’t produce enough eumelanin to get a tan. And it turns out that the same proteins  that trigger MC1R are also involved in pain.

See, melanocytes don’t just make melanin. They also produce a protein called POMC, which then gets cut down into  a bunch of smaller molecules. And the things that POMC can turn  into have a very complicated dance that they do with your perception of pain.

Imagine pain tolerance like a seesaw,  where one side makes your tolerance go up, and the other side makes it go down. POMC and its derivatives have the  ability to load kids, or in this case, its protein derivatives, onto that  seesaw in a very specific way. For instance, there’s one POMC derivative  called MSH that has several jobs, including binding to MC1R and switching  melanocytes to eumelanin-mode.

And one of MSH’s other jobs  is to bind to pain receptors that increase your perception of pain. In other words, if you have a lot of MSH,  you’ll be crying over every paper cut.   But POMC can also be broken down  into a hormone called beta-endorphin, which affects pain tolerance  in the other direction. These bind to your opioid  receptors and reduce pain.

They’re basically acting like homemade  opioid drugs, and the result is that they raise your pain tolerance. Think of it as those beta-endorphin kids  getting on the other side of the seesaw, which keeps your pain tolerance in balance. So essentially those two pain  pathways balance each other out and result in what we think of as  a normal amount of pain tolerance.

And research from 2021 has found  that this seesaw is the key to understanding why redheads have such  a complicated relationship with pain. To be clear, it isn’t about how much  or how little melanin they have. Scientists found that mice with  red-pigmented melanocytes had a higher pain tolerance, even when those mice were  incapable of expressing the melanin.

So the key isn’t in the melanin. It’s in the melanocytes. Mice with fewer melanocytes had higher  pain tolerances than the others.

When the scientists looked at those melanocytes, they found that the same MC1R  mutation that caused their red hair also decreased the amount of  POMC their cells could make. Less POMC means less MSH and less beta-endorphin. So if we go back to our seesaw,  you’d think that this just means that there are fewer kids getting  on but it still stays even, right?

Well, it turns out that our bodies make  all kinds of other stuff that can get on the opioid end of the seesaw. For instance, beta-endorphin isn’t  the only kind of endorphin out there, and you don’t need POMC to make those other ones. If POMC isn’t around to fill  up those opioid receptor seats, these other molecules can take over, swarming the seesaw and setting it off balance.

That includes opioid drugs, which work  by activating the opioid receptors that are all throughout our bodies. And when opioid receptors are activated,  they limit how well your nerves can communicate, which reduces  how much pain you feel. So if your opioid receptors are already  occupied, there are fewer spots for opioid medications to bind to, meaning you need  less in your system to tip the scales.

And what’s really weird is that  this is totally reversible. Scientists could reverse the pain  resistance in those redhead mice by blocking opioid receptors with naloxone,  which is the drug that we normally use to reverse opioid overdoses. Doing so brought the rodents’ pain tolerance  down to the level of a non-redhead.

And that brings us back to the  anesthesia drugs we talked about before. See, anesthesia drugs don’t  target your opioid receptors. The way they work is… well, it’s complicated.

But the point is that they’re not  touching your opioid receptors, which explains why we don’t see the “less  is more” effect for those types of drugs. Now that still doesn’t explain  why they need more anesthesia. That’s a question for future research.

So the mystery of why redheads  respond so differently to these drugs is still very much up in the air. As we learn more, figuring out  how these melanocytes affect pain could even lead to new pain management treatments. And to the redheads watching this video,  while you may not be able to get a tan, at least maybe that paper cut won’t make you cry. [♪ OUTRO]