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Thread: Why do men and women feel pain differently

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    Why do men and women feel pain differently

    Deleted. Sorry, it posted all messed up. I have to repost it.


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    Advisor Angela's Avatar
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    1 members found this post helpful.
    See:
    https://www.nature.com/articles/d41586-019-00895-3

    The short answer: different biological pathways.

    " Results are starting to trickle out, and it’s clear that certain pain pathways vary considerably, with immune cells and hormones having key roles in differing responses."

    How did they get on to it?

    "
    At McGill University in Montreal, Canada, Sorge was investigating how animals develop an extreme sensitivity to touch. To test for this response, Sorge poked the paws of mice using fine hairs, ones that wouldn’t ordinarily bother them. The males behaved as the scientific literature said they would: they yanked their paws back from even the finest of threads.But females remained stoic to Sorge’s gentle pokes and prods1. “It just didn’t work in the females,” recalls Sorge, now a behaviourist at the University of Alabama at Birmingham. "

    Does this mean I have to be even more patient when my husband moans and groans over the (to me) littlest discomfort? :)

    Yet, chronic pain sufferers are more often women. How does that work?

    "To better understand why male and female mice dealt with pain so differently, Sorge and Mogil turned to a pain source that affects all mice. They injured the animals’ sciatic nerves, which run from the lower back down each leg. This led to a form of chronic pain that happens when the body’s pain-detecting system is damaged or malfunctioning. It caused both male and female mice to become extra sensitive to touch.

    Yet even in this case, there were differences. Microglia seemed to have a prominent role in the pain of males, but not in that of female mice2. Sorge and a team of collaborators from three institutions found that, no matter how they blocked microglia, this eliminated the pain hypersensitivity in males alone.


    To better understand why male and female mice dealt with pain so differently, Sorge and Mogil turned to a pain source that affects all mice. They injured the animals’ sciatic nerves, which run from the lower back down each leg. This led to a form of chronic pain that happens when the body’s pain-detecting system is damaged or malfunctioning. It caused both male and female mice to become extra sensitive to touch.

    Yet even in this case, there were differences. Microglia seemed to have a prominent role in the pain of males, but not in that of female mice2. Sorge and a team of collaborators from three institutions found that, no matter how they blocked microglia, this eliminated the pain hypersensitivity in males alone.

    It’s not that females were immune to pain. They were just as bothered by nerve injury as the males were, but they weren’t using microglia to become hypersensitive to touch. Mogil and Sorge wondered whether another immune component, called a T cell, was behind the chronic pain in females. These cells have a known role in pain sensitization in mice.

    Sorge tried the same nerve injury in female mice lacking T cells. They still became hypersensitive to the fine hairs, but the mechanism now seemed to occur through microglia. In females lacking T cells, blocking the activity of microglia prevented this pain response, just as it did in males. And when the researchers transferred T cells back to female mice that were lacking them, the animals stopped using microglia in nerve-injury pain (see ‘Two routes to pain’).


    The team’s findings2, reported in 2015, had a big influence on the pain field, says Greg Dussor, a neuropharmacologist at the University of Texas at Dallas. The results showed that even though everybody’s pain might look similar from the outside, scientists can’t assume it’s the same on the inside.

    If animals can switch between pain pathways, what controls the switch? Researchers have long attributed sex differences in pain perception to oestrogen, a hormone that controls the development of the uterus, ovaries and breasts, and which regulates the menstrual cycle. Oestrogen can either exacerbate or dull pain, depending on its concentration and location. Testosterone, the hormone involved in development of the penis, testes and prostate, as well as of secondary characteristics such as body hair, has received much less attention from pain researchers, although studies suggest it can reduce pain3, and some people with chronic pain take testosterone treatments4.

    In the case of microglia and pain hypersensitivity, Mogil’s research points squarely at testosterone as the control switch for pain pathways. In the 2011 and 2015 studies1,2, when Sorge tested castrated male mice, which have low testosterone levels, the animals exhibited a response similar to females. And when the researchers provided testosterone to castrated males, or to females, the pain pathway switched to one dependent on microglia.

    Since then, researchers have continued to find evidence shoring up the importance of microglia — and the cells’ enzymes and receptors — in male mice experiencing pain. And the phenomenon isn’t restricted to mice: one of Mogil’s collaborators, neuroscientist Michael Salter, also found microglial receptors at work in male rats that had hypersensitivity from nerve injury5. Salter, who is chief of research at the Hospital for Sick Children in Toronto, Canada, is now investigating the question in macaques, which are likely to process pain in a more similar way to humans.

    It’s much harder to investigate these pain pathways in people, but clues are emerging. Neuropharmacologist Ted Price, at the University of Texas at Dallas, and his collaborators have found preliminary evidence, published this month6, of differences in how immune cells contribute to pain in people.
    They’re working with nerve tissue removed from individuals with cancer, whose tumours had invaded their spines. In nerves excised from men experiencing pain, Price’s team found signs of inflammation caused by an immune cell called a macrophage. These cells serve a similar function to microglia. In women who were in pain, however, the more important players seemed to be nerve cells themselves and a short stretch of protein building blocks (called a peptide) that stimulates nerve growth. The results suggest parallels between human and rodent sex differences, says Price."

    "But immune cells and hormones don’t fully explain pain differences. For instance, Sarah Linnstaedt, a translational biologist at the University of North Carolina Medical Center in Chapel Hill, has found hints that some women might have a genetic predisposition to chronic pain. Her team has identified a suite of RNA molecules in the bloodstream that are more likely to be elevated in women who develop chronic neck, shoulder or back pain after a motor-vehicle accident. Many of these RNA molecules are encoded by genes on the X chromosome, of which there are two copies in most women7."

    "Others are thinking about sex-specific pain treatments, too. In a study published online in November 2018, Price and his team reported that a diabetes drug called metformin reduces microglial populations surrounding sensory neurons in the spinal cord. They also showed that the drug blocks pain hypersensitivity from nerve damage only in male mice8. “It didn’t do anything in the females; in fact, it got a little bit worse,” says Price, who has a theory as to why: to enter the nervous system, metformin relies on a protein that’s expressed at higher levels in cells from males. Higher doses didn’t make a difference in females, however, presumably because the medication was trapped outside the nerves.

    Higher doses do help females receiving one of the oldest pain drugs in the pharmacy: morphine. Women and female rodents both usually require higher doses of morphine to achieve the same pain relief as men and male rodents, says Anne Murphy, a neuroscientist at Georgia State University in Atlanta. She’s one of a handful of researchers who was studying sex differences well before the NIH changed its guidelines."

    "There’s at least one drug already on the market that scientists have reason to think might work differently across sexes. In 2018, the US Food and Drug Administration approved migraine treatments based on antibodies against CGRP, a peptide found in the nervous system that is involved in these kinds of headache. Migraines affect three times as many women as men.

    In an as-yet-unpublished study of mice and rats, a team led by Price and Dussor applied CGRP to the thick membrane surrounding the brain. In females, the peptide created a response that looked like a migraine: the animals grimaced and their faces were hypersensitive to touch. In males: “Nothing,” says Dussor. Modern anti-CGRP medicines might work better in women than in men, he adds — but the drug’s clinical trials didn’t check for such effects."

    So, no women aren't more often chronic pain sufferers because they're neurotic either.

    Honestly, to think we know so little about any of this stuff.

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