Researchers at the National Institutes of Health (NIH) have discovered clues as to how our bodies turn sensations such as heat and touch into signals sent to the brain - and how these signals can be altered by inflammation to drive pain. The research focuses on the nerve cells in the skin that help us detect the location, intensity, and emotional quality of touch, known as somatosensory neurons. By combining advanced imaging techniques with detailed molecular analysis, the researchers explored how heat and touch activate different types of receptor cells in mice.
"To develop better treatments for pain, it's critical that we deepen our understanding of the biology behind how sensory signals are received, transmitted, and ultimately perceived by the brain," said Alex Chesler, Ph.D., co-author of the study and senior investigator at NIH. "Over the past few years, we developed a platform for watching sensation in action, revealing new details about the cells and molecules required and, in this study, how inflammation triggers pain."
The research revealed how different types of cells were "called into action" depending on whether the stimulus was innocuous, such as gentle warmth or touch, or noxious, meaning a stimulus strong enough to potentially cause damage to normal tissue. For example, heat and gentle touch were transmitted by entirely different types of cells. When the stimulus was more intense, the nerve cells began to overlap in their roles for transmitting the sensations of heat and pressure, providing an explanation for how cells detect and distinguish between innocuous and noxious stimuli.
Inflammation is well known to be linked to pain, but the understanding of what is happening on the cellular and molecular levels is less clear. In their experiments, researchers injected prostaglandin E2 into the skin, a molecule that causes inflammation and drives pain. With the inflammatory response set into motion, researchers found that certain neurons used for signaling pain (nociceptors) became active and sensitized to heat for a long duration, demonstrating the cellular processes at play.
"This explains how inflammation drives ongoing pain and why heat becomes more painful," said Nick Ryba, Ph.D., co-author and senior investigator at NIH. "However, what was unexpected was that touch detection remained unchanged."
The study found that inflammation-related hypersensitivity to touch, known as tactile allodynia, was caused by the ongoing nociceptor activity induced by inflammation superimposed on the normal sensation of touch. This finding is consistent with previous research at NIH showing that the ion channel PIEZO2 plays a crucial role in this type of pain .
The research is part of a long-term collaboration between the groups headed by Drs. Chesler and Ryba. Together these labs conduct basic research focusing on how sensory input is detected and processed by the brain to evoke specific behaviors. According to Dr. Chesler, even though this study is in mice, the similarities to humans in the neural pathways far outweigh the differences, so the findings hold important implications for people.
"By learning more about how touch and heat are signaled in the body, we're identifying new clues for treating pain," said Dr. Chesler. "Our study shows how different types of pain may benefit from different types of treatments. In short, by identifying exactly which cells and molecules 'turn up the volume' of different types of pain, we may be able to identify the 'switches' that can turn the volume down."
The research was led by investigators in the Sensory Cells and Circuits Lab at NIH's National Center for Complementary and Integrative Health and the Taste and Smell Section at NIH's National Institute of Dental and Craniofacial Research.
About the National Center for Complementary and Integrative Health (NCCIH): NCCIH's mission is to define, through rigorous scientific investigation, the usefulness and safety of complementary and integrative health approaches and their roles in improving health and health care. To learn more about NCCIH and its programs, visit https://www.nccih.nih.gov .
About the National Institutes of Health (NIH):
