PAIN ain’t the same in boys as it is in girls

The basic theme of these GEITP emails is gene-environment interactions. In the case of this topic, the gene differences occur in males vs females, whereas the environmental signal is induction of PAIN to the individual (mouse or human). At first, studies in mice indicated that pain hypersensitivity results from remarkably different pathways in males and females — reflecting distinct immune-cell types and hormones that contribute to the “discomfort” signal. It has been suggested that no other field of science has identified such striking sex differences; this research could open the door for new medical (and pharmacological) advances.

For example, about 20% of people worldwide experience chronic pain — and the majority are women. Today, the pharmaceutical market offers the same pain drugs to everyone. However, if the roots of pain are different, some drugs might work better in some people than in others. Moreover, people might require different pain medications when hormone levels fluctuate throughout life. It is predicted that future pain medications will be tailored to individuals — and that gender will be a key factor in those personalized prescriptions.

Pain occurs when neural sensors in the skin, muscles, joints or organs register a potentially harmful sensation, such as heat or tissue damage.

They send signals through peripheral nerves to the spinal cord, activating other nerves that send signals to the brainstem and on to the cerebral cortex, which interprets those signals as “ouch!” or “not so ouch!” But pain happens in many ways, and diverse chemical pathways contribute. Some pain types are distinguished by timing. There is the acute response to something hot, sharp or otherwise noxious, and there is long-term, chronic pain that might persist even after the initial injury has healed.

One study involved injury to the animals’ sciatic nerves (which run from the lower back down each hindleg); this led to a form of chronic pain that

happens when the body’s pain-detecting system is damaged or malfunctioning — causing both male and female mice to become extra-sensitive to touch. Yet, even in this case, there were sex differences: microglia (glial cells that function as macrophages (scavengers) in the central nervous system and form part of the reticuloendothelial system) appeared to have a prominent role in the pain of males, but not in that of female mice. Scientists found that, no matter how they blocked microglia, this eliminated pain hypersensitivity in males alone.

By studying the same nerve injury in female mice lacking T cells, they still became pain-hypersensitive, but now the mechanism 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 females stopped using microglia in nerve-injury pain [see the figure in the attached editorial]. This entire article [attached] makes for fascinating bedtime reading. 🙂


Nature 28 Mar 2o19; 567: 448-450

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