Scientists have uncovered differences between the sexes in the way pain is produced, pointing to potential new ways to target treatment for women and men.
Researchers at the University of Arizona have identified functional sex differences in nociceptors, the nerve cells that produce pain.
This discovery of "male nociceptors and female nociceptors" may help scientists develop precise medicines for managing pain that are tailored to a patient's sex.
Study author Frank Porreca, the research director of the Comprehensive Center for Pain & Addiction at the University of Arizona Health Sciences, said in statement: "The outcomes of our study were strikingly consistent and support the remarkable conclusion that nociceptors, the fundamental building blocks of pain, are different in males and females.
"This provides an opportunity to treat pain specifically and potentially better in men or women, and that's what we're trying to do."
For the study, the team used tissue samples from female and male mice, non-human primates and humans to examine how their nociceptor cells, located near the spinal cord, responded to stimuli.
Nociceptors are sensory receptors that trigger the perception of pain when they are activated by injury, illness or damage to the body. They help keep us safe, for example, by allowing us to sense pain when we touch something hot, so that we remove our hand from the source of danger and don't damage ourselves further.
Specifically, the researchers chose to test how the cells reacted to two substances, prolactin—a hormone responsible for lactation and breast development—and orexin B—a neurotransmitter that helps to regulate sleep. They selected these substances based on a previous study on chronic pain, which found that they had a sensitizing effect on nociceptors.
Then, they tested how prolactin and orexin B affect the extent to which nociceptors react to low-intensity, pain-producing stimuli. The way we experience pain differs in intensity, depending on the stimulus. While touching a hot stove is high-intensity, a piece of clothing rubbing on sunburn is low intensity—but both are detected by the body as pain.
However, certain substances—including painkillers—can change the threshold at which pain is detected. This is how painkillers like Ibuprofen work, as they block nociceptor activation when mild-to-moderate pain is being signaled.
After examining the tissue samples, the researchers found that what changes the thresholds of the nociceptors was different in females and males. They found that prolactin only sensitized female cells and orexin B only sensitized male cells.
"The startling conclusion from these studies is that there are male nociceptors and female nociceptors, something that has never previously been recognized," said Porreca.
They also found that blocking prolactin signaling reduced nociceptor activation in females, but had no effect in males. Meanwhile, blocking orexin B signaling worked in males and not females.
According to the researchers, the findings suggest that the underlying mechanisms that result in us perceiving pain are different between the sexes.
They hope that this research will help scientists find new precise ways to treat pain, particularly among conditions more common among women, such as migraine and fibromyalgia.
The full findings of the study were published in the journal BRAIN.
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