Sexual differences in pain sensation could be due to differing pain receptors

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Pain is highly personal. What to some doesn’t even deserve the name, for others can be unbereable. Now, we just discovered a difference in how we feel it: men and women have different pain receptors.

Recent research1 has demonstrated in rodents and, importantly, primates including humans, that there are sex differences in pain receptors, also called nociceptors. According to the results of the study, the hormone prolactin sensitizes dorsal root ganglion neurons in females, but not in males, increasing the sensation of pain from mild to severe. Similarly, the neurotransmitter orexin B increases pain sensation in males, but not females.

Although the influence of prolactin on pain sensation in female rodents had been previously identified, these in vitro experiments on neurons recovered from both male and female rodents, non-human primates and humans demonstrated that this finding is evolutionarily conserved. In addition, they identified orexin B as an analogous effector to prolactin in male neurons from three different species (mice, macaques, and humans).

While prolactin is a typically female hormone, as it is related to lactation, orexin B is mostly related to sleep regulation, which not only males need so this molecule probably plays others, yet undetermined, roles in our physiology.

These findings are very relevant, particularly from a clinical point of view, as most treatments are not specifically tested in women, and this difference in sensation, together with other sex specific traits, make personalized medicine a MUST. We cannot be treating pain equally to both sexes when it is demonstrated that, at least in pain sensation, men and women are different.

References

  1. Harrison Stratton, Grace Lee, Mahdi Dolatyari, Andre Ghetti, Tamara Cotta, Stefanie Mitchell, Xu Yue, Mohab Ibrahim, Nicolas Dumaire, Lyuba Salih, Aubin Moutal, Liberty François-Moutal, Laurent Martin, Edita Navratilova, Frank Porreca (2024) Nociceptors are functionally male or female: from mouse to monkey to man Brain doi:10.1093/brain/awae179

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