When people discuss their experiences of getting tattoos, sustaining sports injuries or giving birth, a question often comes up: Do people of different sexes experience pain differently?
It turns out that, on a cellular level, there do seem to be inherent differences in how males and females process painful stimuli. But the question of which sex — if either — has a higher pain tolerance has a fuzzier answer.
For a person to feel pain, sensory neurons called nociceptors detect painful stimuli and then send a signal to the brain for interpretation. These painful stimuli include extreme temperatures, mechanical pressure and inflammation. People show differences in how they perceive each stimulus, and these differences stem from various factors, including a person's sex.
Several studies have reported that women have higher pain sensitivity and a lower pain threshold than men. For instance, a 2012 study that examined how men and women respond to physical pressure found that women are more sensitive to mechanical pain than men are. In another study, men and women were asked to indicate when they felt a heat stimulus and judge its intensity. It suggested women have lower pain thresholds to heat than men.
"It is well known that females are more sensitive to pain than males," said Jeffrey Mogil, a professor of behavioral neuroscience at McGill University who studies sex differences in pain. "This has been shown in humans in hundreds of studies; not all of them are statistically significant, but essentially all of them go in the same direction," Mogil told Live Science.
However, some studies actually show the opposite.
Related: Do women get cold more easily than men?
In a study published in 2023, researchers recruited 22 adolescents — 12 females and 10 males — for a thermal pain sensitivity test. These participants were exposed to hot and cold stimuli and then asked to rate the intensity of their pain. The males rated higher pain intensity to both stimuli than the females did.
Still other studies have suggested that there are no differences in how males and females respond to pain-inducing heat.
This dissensus exists among scientists because there are no "meaningful" metrics for measuring pain tolerance, said Frank Porreca, a professor of neuroscience at the University of Arizona. A given person's pain threshold and tolerance tend to vary across tests and environments; plus, some studies find that females are more reliable test subjects than males, providing more consistent ratings of their pain.
Porreca studies mechanisms that can promote pain, and he and his team recently discovered that males' and females' nociceptors are activated by different substances. That is, the first step for pain perception differs between the sexes.
Mogil told Live Science that it had not previously been shown that features of the nociceptors themselves are sex-dependent.
It was known that pain stimuli need to surpass certain thresholds to activate nociceptors. Usually, a low-intensity stimulus, like drinking cold water, would not activate nociceptors — but if you have a sore in your mouth, the nociceptors there would be activated. Porreca explained that, in this scenario, the threshold for nociceptor activation is lowered, and his team wanted to know if this "sensitization" was sex-dependent.
To investigate, they sampled nociceptor cells from the dorsal root ganglion, a terminal near the spinal cord through which sensory information passes to the central nervous system. The team took cells from male and female mice, nonhuman primates and humans and exposed the cells to various substances.
Previous studies have implicated the hormone prolactin in females' response to pain and a chemical messenger called orexin in males' pain responses, so these seemed like the perfect agents for the experiment. The results showed that the cells behaved differently when exposed to either substance across all of the sampled species.
Prolactin lowered the threshold for nociceptor activation in females but didn't affect males. Conversely, orexin sensitized male cells but had no effect on the female cells. Both substances naturally occur in both sexes but in different concentrations.
"The nociceptors that we derive from either male or female animals or postmortem human donors are quite different in what processes produce this lowering of thresholds," Porreca said.
He added that this discovery could help devise pain therapies that would be optimized for men and women, especially as "most of the world's pain patients are women." For example, the chronic-pain condition fibromyalgia is more common in women than men in the U.S.
"Regardless of which sex is more sensitive to pain, there's increasing evidence, like this paper here, that the circuitry going on behind the scenes is different circuitry in males and females," Mogil said. "The system is actually a different system in males versus females, and that's actually the more interesting part."
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