We can never know how somebody else experiences pain – especially when it’s caused by something we’ll never experience ourselves. It’s a big reason why people get so invested in things like the existence of man flu, or whether childbirth is more painful than getting kicked in the balls.
But while the jury’s likely to stay out on those particular examples for some time, a new study published in the journal Brain has shed some light on just why they’re such favorites. Pain, it seems, does not come to male and female bodies equally – and now we know why.
“Women are disproportionately impacted by the burden of chronic pain,” explains the paper. “They are more likely than men to report low back pain, neck pain, orofacial pain and neuropathic pain, and twice as many women report common migraines or headaches. In quantitative evaluation of experimentally induced pain in humans, women show more pain sensitivity than men across several noxious modalities, including mechanical-, electrical-, thermal- and chemical-induced pain.”
Despite this clear disparity, for decades the general scientific consensus on pain perception was that it affected male and female bodies in basically the same way. The problem was, this conclusion wasn’t really based on anything: “A male-biased approach has dominated neuroscience research, including pain, typically with no rationale provided,” the authors note.
“In the field of synaptic physiology, mechanisms of neuromodulation have relied almost exclusively on research in male or unsexed animals, even as examples of sexual dimorphism in synaptic circuitry and plasticity have been uncovered,” they add.
The new study has two big advantages over previous research, then: first, it included female subjects; and second, it included human subjects.
“Given the importance of understanding the neurobiological underpinnings of chronic pain across sex, we investigated mechanisms of neuronal hyperexcitability in the rat and human superficial dorsal horn of males and females,” the researchers explain.
Now, if you’re wondering how you missed the fact that you had a horn all this time, don’t worry: the superficial dorsal horn is a distinct region on the outskirts of the gray matter inside your spinal cord. When the researchers examined this spinal tissue, which had been donated post-mortem, they discovered something interesting.
First things first: there’s a specific kind of protein that lives in our spinal cords known as brain-derived neurotrophic factor, or BDNF for short. It plays an important and complex role in pain processing, amplifying pain signals in the spinal cord over short timespans and doing the opposite long-term.
That’s not new – the BDNF gene was first discovered a full 40 years ago now, and many studies have already investigated its role in pain perception. But here’s the thing: remember how we said before that almost all those studies were exclusively conducted in male animals and humans?
“We discovered that … a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats,” explains the paper.
“Unlike males, [BDNF] … failed to downregulate inhibitory signaling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B and pGluN2B) in female rats,” it notes. “Importantly, this sex difference in spinal pain processing was conserved from rodents to humans.”
In other words: male and female bodies – and the BDNF gene in particular – really do process pain differently. But why?
“We conclude that this sex difference in response to BDNF is hormonally mediated,” the authors write. That would agree with previous studies which blame women’s pain on their higher estrogen levels, but the researchers also have a crucial piece of evidence in their corner: when they removed the ovaries of female rodents, the difference in pain signaling between sexes disappeared.
The discovery has major implications, and not just for winning arguments about whether men are weak little babies, actually. It’s an important step towards the development of more personalized therapies, honed as far as possible for the patient’s individual needs, as well as new drugs for pain management specifically.
“Developing new pain drugs requires a detailed understanding of how pain is processed at the biological level,” said Annemarie Dedek, lead author of the study. “This new discovery lays the foundation for the development of new treatments to help those suffering from chronic pain.”