Women perceive pain differently than men. Researchers have now discovered a mechanism in mice that is involved in this phenomenon. Accordingly, the female sex hormones stimulate estrogen and progesterone in the spinal cord’s skins to produce a pain relieving opioid. If the researchers blocked this signal path, female mice became much more pain -sensitive. The findings could help find new treatments for chronic pain.
The regulatory T cells of the immune system, for short T-REG, are primarily known for dampening immune activity and thus preventing autoimmune diseases and excessive inflammatory reactions. They also help to regenerate damaged tissue again. However, earlier studies have indicated that these defense cells could also play a role in addition to their function for the immune system to modulate the perception of pain. So far, however, the underlying mechanisms were unclear.
Gender differences
“We examined how T-Regs regulate the perception of pain in mice,” reports a team around Élora Midavaine from the University of California in San Francisco. For this purpose, the researchers injected a poison that selectively destroys the regulatory T cells in the spinal crews. Then they tested the extent to which the pain sensitivity of the mice changed.
To the surprise of the researchers, it turned out that female mice without T-Regs reacted much more pain-sensitive to mechanical stimuli than normal. Male mice, on the other hand, showed no shift in their pain threshold when the regulatory T cells were lost. The reaction to heat and cold stimuli remained unchanged in mice of both sexes. “This indicates that the regulatory T cells in the spinal corners regulate the pain threshold for mechanical stimuli in a gender-dependent way,” explains the research team.
Pain inhibition by immune cells
In other experiments, Midavaine and her colleagues found that the female sex hormones estrogen and progesterone have an important influence on the pain-regulating function of the T-Regs. Under the influence of the two hormones, the T-REGs poured the pain relieving opioid enkephalin in the spinal corners. This in turn ensures that painful signals from the mechanical receptors in the skin get to the spinal cord, but are not forwarded from there to the brain. As a result, the perception of pain is steamed.
If the researchers removed the ovaries that are responsible for the production of sex hormones, or blocked the estrogen receptors, the T-Regs no longer showed pain relieving skills. On the other hand, the researching mice without ovary sprayed estrogen and progesterone, the pain inhibition worked again. This confirms that the immune cells only have their analgesic effects under the influence of the female sex hormones. The immune-regulatory function of the T-Regs, on the other hand, was independent of the sex hormones.
“The fact that there is a gender -dependent influence on these cells – driven by estrogen and progesterone – and that it is not related to an immune function is very unusual,” said Midavaine. However, this effect could explain why women perceive pain differently than men. Midavaine and her team want to clarify the exact mechanism in future studies. Maybe the findings could help find new approaches to the treatment of chronic pain.
Source: Élora Midavaine (University of California, San Francisco, USA) et al., Science, Doi: 10.1126/science.adq6531