summary: Scientists have discovered that female hormones such as estrogen and progesterone can cause immune cells near the spinal cord, releasing natural opioids and relieve pain before they reach the brain. These immune cells, known as T-regulatory cells (T-Regs), are located in the meninges and produce the analgesic molecule enkephalin in response to hormone signals.
This effect appears to be specific to women, providing insight into why some pain treatments work better for women and why postmenopausal women experience more chronic pain. This newly discovered mechanism could lead to gender-specific and innovative treatments for millions of people affected by chronic pain.
Important facts:
- Hormones-driven relaxation: Estrogen and progesterone encourage T-regs to release natural opioids.
- Gender Reaction: Female mice without T-Regs became more sensitive to pain. The men weren’t.
- Treatment possibilities: Engineering T-Regs may offer new approaches for chronic pain relief.
sauce: UCSF
Scientists have discovered a new mechanism that acts through immune cells and points to how to treat chronic pain.
A new study from researchers at UC San Francisco found that by creating immune cells near the spinal cord, pain can be reduced. This will stop the pain signal before it reaches the brain.
This finding could help develop new therapies for chronic pain. It may also explain why some painkillers work better for women than men, and why postmenopausal women experience more pain.
This study uncovers an entirely new role for T-regulated immune cells (T-Regs), known for their ability to reduce inflammation.
“The fact that these cells, driven by estrogen and progesterone, have a sex-dependent effect, and that it has absolutely nothing to do with immune function, is very unusual,” said Dr. Erola Midavain, a postdoctoral researcher. She was the first author of the study, and in part was funded by the National Institutes of Health.
It will be displayed on April 4th Science.
The researchers looked at T-Reg, a protective layer that envelops the mouse’s brain and spinal cord. Previously, scientists thought these tissues, called meninges, could help protect the central nervous system and eliminate waste. T-Reg has only been discovered there in recent years.
“What we’re showing now is that the immune system actually uses the meninges to communicate with distant neurons that detect skin sensations,” says Maseen Kashem, MD, assistant professor in dermatology.
“This is something we never knew before.”
That communication often begins when neurons near the skin feel something that can cause pain. The neurons then send signals to the spinal cord.
The team found that the meninges surrounding the lower part of the spinal cord are abundant in T-Reg, which is rich. To find out what their function is, researchers knocked out the cells with toxins.
The effect was noticeable. Without TREGS, female mice were more sensitive to pain, while male mice did not. This gender difference suggests that female mice rely more on T-Regs to manage pain.
“It was both charming and inexplicable,” Kashem said. “In fact, I was skeptical at first.”
Further experiments revealed the relationship between T-Regs and female hormones.
How the hormones do this is a question the team hopes to answer in future research. However, even without that understanding, this recognition of this gender-dependent pathway can lead to a much-needed new approach to treating pain.
In the short term, it may help physicians choose more effective medications for patients, depending on their gender. For example, certain migraine treatments are known to work better for women than for men.
This is especially useful for women who have experienced menopause and are no longer producing estrogen or progesterone. Many of them experience chronic pain.
Researchers are beginning to explore the possibility of engineering T-Reg to constantly produce enkephalin in both men and women.
“If that approach is successful, it could really change the lives of nearly 20% of Americans experiencing chronic pain that are not properly treated,” Basbaum said.
author: Other authors on this study include Beatrice Moraes, Jorge Benitez, Cian Rodriguez, Joa Braz, Nathan Kochal, Walter Eckalver of Uxf, Lynn Tian, Max Planck Florida Institute, Anna Domingos of Oxford University, and John E.
Funding: Part of this study is funded by the National Institutes of Health Grant (T32AR007175-44, NSR35NS097306). See our research for other funders.
About this pain research news
author: Robin Marks
sauce: UCSF
contact: Robin Marks – UCSF
image: This image is credited to Neuroscience News
Original research: Closed access.
“Meningeal regulatory T cells inhibit nociception in female mice“Written by Erola Midavain et al. Science
Abstract
Meningeal regulatory T cells inhibit nociception in female mice
T cells have emerged as orchestrators of pain amplification, but the mechanisms that control T cells do not control pain treatment.
Regulatory T cells (treg Cells) may inhibit nociception through mechanisms that do not depend on their ability to regulate immune activation and tissue repair.
Site-specific depletion or expansion of meningeal Treg Cells (Mt)reg Cells) In mice, it led to female-specific and sex hormone-dependent regulation of mechanical sensitivity.
Specifically, MTreg The cells produced the endogenous opioid enkephalin, which exerts antinociceptive effects through the delta opioid receptor expressed by MRGPRD.+ Sensory neurons.
Enkephalin suppresses nociceptive processing, which was essential for Treg Cell-mediated immunosuppression.
Therefore, our findings revealed sexual dimorphic immunological circuits that suppress nociception and established treg Cells as sentinels for pain homeostasis.
