Researchers from the Taste and Smell Section at the National Institute of Dental and Craniofacial Research and the Sensory Cells and Circuits Lab at the National Center for Complementary and Integrative Health, both part of the NIH, have uncovered the molecular and cellular mechanisms involved in sensing inflammatory pain and heat.
A recent NIH-supported study has uncovered how the body turns sensations like touch and heat into signals and sends them to the brain, and how inflammation can alter these signals to cause pain. This study focused on nerve cells, also known as somatosensory neurons, in the skin, which help determine the intensity and emotional quality of pain. The researchers have found that touch and heat activate various types of receptor cells in the mice by combining molecular analysis and advanced imaging techniques.
Alex Chesler, Ph.D., a senior scientist at NIH and co-author of one study, said, “It is necessary to have a deep understanding of biology that explains how these sensory signals are transmitted and perceived by the brain to find good treatments for the pain. In the last few years, we have developed a platform to watch the action of sensation, reveal the new information about the molecules and cells needed, and how pain causes inflammation.”
This study has shown how various cell types are called into action based on the stimulus, such as gentle touch, warmth, or noxious stimuli strong enough to damage normal tissue. For example, gentle touch and heat are transmitted by different types of cells. The nerve cells start to overlap, transmitting the sensations of pressure and heat, which explains how the cells can detect and differentiate between noxious and innocuous stimuli in intense stimuli.
Inflammation is linked to pain, but it is unclear how it occurs at the molecular and cellular levels. In their experiments, researchers administered prostaglandin E2, a molecule known to cause inflammation on skin, to study its effects on pain signaling. It is a molecule that can cause inflammation and lead to pain. They have found that specific neurons are used for signaling pain, such as nociceptors, which are active and sensitized to heat for a long time, indicating the cellular mechanisms involved in initiating the inflammatory response.
Nick Ryba, Ph.D., a senior investigator and co-author at NIH, said, “This clarifies how inflammation causes pain and heat to become sensitive to heat. Though it was unexpected that the touch detection was not changed.”
The hypersensitive inflammation related to touch is known as tactile allodynia. It occurred due to the ongoing activity of nociceptors, which are developed by inflammation, superimposed on normal touch sensation. The consistent results from earlier research at NIH showed that the ion channel PIEZO2 plays an important role in pain.
This research is collaborative research between Drs. Ryba and Chesler groups. They have conducted basic research together that focuses on how the brain detects and processes sensory signals to trigger certain behaviour. According to Dr. Chesler, this study was conducted on mice. However, the connection in neural pathways surpasses the difference, and the results have important implications for humans.
Dr. Chesler said that by determining how heat and touch are signaled in the body, we may discover new findings to treat pain. Our study showed that different types of pain may benefit from various treatments. In brief, to identify which molecules and cells are involved in various types of pain, scientists may one day discover a “switch” that can turn off pain.
Reference: NIH study reveals how inflammation makes touch painful. National Institutes of Health (NIH). Accessed April 24, 2025. https://www.nih.gov/news-events/news-releases/nih-study-reveals-how-inflammation-makes-touch-painful
