How Does Inflammation Trigger Pain? Researchers Now Know

National Institutes of Health researchers are breaking down how our bodies turn heat and touch into signals sent to the brain—and how these signals can be altered by inflammation to drive pain. 

The NIH is looking into somatosensory neurons—nerve cells in the skin that help determine the “location, intensity and emotional quality of touch,” according to a press release—in a murine study population. Investigators in the Sensory Cells and Circuits Lab at the NIH’s National Center for Complementary and Integrative Health and the National Smell and Taste Center at the National Institute of Dental and Craniofacial Research used advanced imaging and detailed molecular analysis to explore 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, PhD, a co-author of the study and senior investigator at the NIH, in a press statement. “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.”

According to the investigators, different types of cells were “called into action” depending on whether the stimulus was innocuous, such as gentle warmth or touch, or noxious (defined as a stimulus strong enough to potentially cause damage to normal tissue). They discovered that heat and gentle touch were transmitted by entirely different types of cells. 

As the stimulus intensified, “the nerve cells began to overlap in their roles for transmitting the sensations of heat and pressure.” This recognition of the intensity of stimuli is the beginning of the explanation for how cells detect and distinguish between innocuous and noxious stimuli.
Inflammation’s link to pain is well documented, but less is known about the relationship’s molecular and cellular basis. To that end, researchers injected prostaglandin E2—a molecule that causes inflammation and drives pain—into the skin. With the inflammatory response set into motion, researchers found that pain-signaling 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, PhD, a co-author and senior investigator at the NIH. “However, what was unexpected was that touch detection remained unchanged.” 

The study found that hypersensitivity to touch as a result of inflammation (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.”

 Chesler said the similarities between humans and mice 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,” Chesler said. “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 article, “A Distributed Coding Logic for Sermocination and Inflammatory Pain,” was published online April 23, 2025, in the journal Nature. 

—PMN Staff

Based on a press release from the NIH.