As a ballet dancer in a former life, countless rehearsal hours in pointe shoes once landed me in a podiatrist’s office with a particularly inflamed ingrown toenail. To my surprise – and the doctor’s – a typical injection of local anesthesia did nothing to numb the searing pain as his knife dug into my big toe. It was not until a second full injection made my toe the size of a golf ball that I became blissfully unaware of the pain.
Was my hair color to blame? It is, after all, a rumor every redhead has heard: we feel more pain and need more painkillers.
A look at the published research suggests that the genes that determine my hair color may play a role, but the science itself is murky.
What makes a redhead?
Our luster-filled locks derive from a pair of mutated genes. For most people, hair color is determined by the melanocortin-1 receptor, or MC1R gene that leads to the production of a brown-black melanin pigment called eumelanin. The more eumelanin created by this gene, the darker and blacker the hair.
The MC1R gene that determines an individual’s hair color is located on humans’ 16th chromosome. Image by Megan Scott
Most redheads have a recessive version of the MC1R gene caused by the pairing of three possible mutant alleles. The resulting gene expression shuts off eumelanin production, shifting the dominant pigment to the reddish-toned pheomelanin.
McGill University behavioral neuroscientist Jeffrey Mogil examined the gene as part of his research on the perception and inhibition of pain. “The purpose of this MC1R gene is to produce dark pigments. If it works, it does, and if it doesn’t, it produces pigment that isn’t dark like it’s supposed to be. So, it really is a dysfunction,” he said.
But MC1R doesn’t just influence hair color. The pigments also contribute to eye hue and skin tone. Excess pheomelanin corresponds to fairer skin, and individuals with freckles have an 85 percent greater chance of having at least one mutant MC1R allele in their genes. MC1R-related redhead expression is also linked with increased ultraviolet radiation sensitivity and skin cancer risk.
Eumelanin has a brown-black tone, but some mutations of the MC1R gene shut off nearly all eumelanin production, leaving only the red-yellow hues of pheomelanin. Image by Megan Scott
The pain of being a redhead
Melanocortin-1 receptors appear in the midbrain where pain perception is regulated, so there is evidence the gene also influences our response to injury and discomfort. Since 2000, a handful of small studies have examined the connection between redheadedness and pain, and on the surface, the results appear to conflict.
…if you are walking down the street, there is nothing that you can see in somebody that will tell you how much anesthesia they need, except red hair.-Daniel Sessler
A Louisville University team led by anesthesiologist Daniel Sessler found that redheads require 19 percent more inhaled, general anesthesia than their dark-haired counterparts.
“There is no other phenotype for anesthesia,” Sessler, now the chair of the Department of Outcomes Research at the Cleveland Clinic, said. “Basically, if you are walking down the street, there is nothing that you can see in somebody that will tell you how much anesthesia they need, except red hair. And it is a relative amount.”
They also found injections of the anesthetic lidocaine were less effective in redheads, a sign that they might require more of the drug.
“If you give them local anesthesia, they don’t get as much pain relief as other people do.”
Around the same time however, Mogil’s team was investigating aspects of MC1R’s role in pain perception. Redheads of both genders needed less of the opioid morphine to dull their pain, while redheaded women needed less of a little-used kappa-opioid drug sometimes used to treat labor pain.
Studies have shown redheads need more anesthesia but fewer opioid painkillers than individuals with other hair colors. Photo by Marcos Brindicci/Reuters
But the contrasting requirements of anesthesia and analgesics like opioids in redheads doesn’t necessarily mean one research group has incorrect findings. Anesthesia and analgesics are two separate phenomena. The first numbs pain and other senses at the same time. The later kills pain without desensitizing touch, temperature or other perceptions.
Because the two treatments work in different ways in the brain and central nervous system, it’s plausible that they are affected differently by redheads’ MCR-1 genes.
But when it comes to pain perception, the two groups found contrasting results that are harder to reconcile. Sessler’s team found that ginger-locked individuals are also more sensitive to pain perception tied to hot and cold temperatures, but Mogil’s data suggested orange-hued subjects are less sensitive to electric shock pain.
How a brain gets hooked on opioids By Nsikan Akpan, Julia Griffin Understanding the science of pain, with the help of virtual reality By PBS NewsHour“There’s no obvious way to reconcile the data, to be honest, and that’s always been disappointing to people,” Mogil said. “You hear when people talk about it, half the time they’re saying my story and half the time they’re saying the other story. I know it’s frustrating to redheads, who would like to know whether they are more or less sensitive [to pain], and that’s still unclear.”
But the results do confirm one thing: redheads do indeed perceive pain differently than those with other hair colors.
Redhead opioid sensitivity
Whether a redhead’s relationship with pain influences susceptibility to dependence on painkillers like opioids remains to be seen.
Past studies have shown that twins and other relatives of opioid abusers are more likely to become addicted themselves, suggesting genetics may factor into susceptibility. But MC1R’s influence has yet to be investigated.
Mogil’s results that indicate redheads require fewer opioids could signal they will take fewer of the pills and have a lower risk of dependency than individuals with other hair colors. But Sessler said his findings on pain perception may extend to a higher risk of abuse.
“If redheads are more sensitive to pain, they are more likely to get opioids and need more opioids than other people,” he said.
Ultimately, as is the case with so many scientific inquiries, the refrain remains the same: more research (and redheads) are needed.
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