Why Heat and Touch Can Become Painful: What an NIH Study Found

If you have ever stepped into a warm shower with a sunburn, you know the feeling. Water that would normally feel pleasant suddenly stings. A cotton T-shirt, which you would not notice on a normal day, scrapes like sandpaper. Nothing about the water or the fabric has changed. Something about you has.

That shift, where ordinary warmth and ordinary touch start to hurt, is one of the most common experiences in pain, and one of the least understood. A study from scientists at the National Institutes of Health (NIH), published in Nature in April 2025, offers one of the clearest explanations yet of how it happens, and why heat and touch turn painful by different routes.

What the researchers set out to answer

The study was led by Alexander Chesler of the National Center for Complementary and Integrative Health (NCCIH) and Nicholas Ryba of the National Institute of Dental and Craniofacial Research, with first author Nima Ghitani. Both institutes are part of NIH.

Their question was a basic one. Your skin is wired to sensory neurons that respond to warmth, cold, pressure and injury. Scientists have long debated how the nervous system tells these apart. One idea is that each sensation has its own dedicated line, a set of "pain neurons" that fire only for pain. Another is that sensations are encoded by patterns of activity across many different neurons at once.

To test this, the team recorded activity from large numbers of sensory neurons in living mice while applying heat and mechanical pressure at different strengths. They then identified which molecular type each responding neuron belonged to, so they could see not just that a neuron fired, but what kind of neuron it was.

Finding 1: gentle and painful sensations are coded differently

At low intensities, the picture was tidy. Gentle warmth and light touch were detected by separate groups of neurons that barely overlapped.

As the stimuli became strong enough to threaten tissue damage, that separation broke down. Many of the same neurons responded to intense heat and to intense pressure. In other words, the signal for "this might injure you" was not carried by one exclusive pathway. It came from a broader pattern of activity across overlapping neuron groups, which the authors describe as a distributed coding logic.

That matters because it helps explain why pain is so hard to switch off with a single, precise drug. There may be no single pain wire to cut.

Finding 2: inflammation makes heat-sensing neurons hypersensitive

Next, the team mimicked inflammation by injecting prostaglandin E2, a chemical the body releases at sites of injury and infection. It is the same molecule that common anti-inflammatory painkillers such as ibuprofen work to reduce.

Two things happened. Pain-sensing neurons, called nociceptors, became active and stayed active for a long time. And certain groups of those nociceptors became far more sensitive to heat, so that temperatures they would normally ignore now set them off.

The heat sensitization depended on TRPV1, a protein on nerve endings that responds to heat and to capsaicin, the compound that makes chili peppers burn. TRPV1's discovery earned David Julius a share of the 2021 Nobel Prize in Physiology or Medicine. The new study shows that, during inflammation, TRPV1 in specific nociceptor groups is what turns warmth into a burning sensation. That is the biology behind the sunburned shower.

Finding 3: painful touch works through a different route

The most surprising result concerned touch. When gentle touch becomes painful, a symptom called tactile allodynia, a reasonable guess would be that inflammation makes the touch-sensing neurons themselves more sensitive.

That is not what the researchers found. The neurons that detect light touch responded the same way before and after inflammation. Their sensitivity did not change.

Instead, painful touch appeared to depend on the ongoing firing of nociceptors. When the team blocked nociceptor activity, touch no longer became painful. The working explanation is that persistent pain signaling changes how the nervous system interprets ordinary touch signals further along the pathway, rather than changing the touch sensors in the skin.

Put simply, inflammation makes heat hurt by sensitizing heat detectors, and it makes touch hurt by keeping pain neurons switched on. Two symptoms that feel similar have different causes.

Why this matters for pain treatment

Chronic pain is common. In 2023, 24.3 percent of U.S. adults reported chronic pain, and 8.5 percent had high-impact chronic pain that frequently limited their daily life or work, according to the CDC's National Center for Health Statistics.

Many existing treatments act broadly. Opioids dampen pain signaling across the nervous system and carry serious risks. Anti-inflammatory drugs reduce prostaglandins everywhere, not only where the pain is. If heat pain and touch pain run through different mechanisms, it becomes possible to imagine treatments that target one without the side effects of blunting the other, or of blunting normal sensation altogether. The researchers say their findings could help guide more targeted therapies for specific types of pain.

The work also sharpens how clinicians think about allodynia. If painful touch is driven by ongoing nociceptor activity, then reducing that activity at its source, rather than numbing touch, may be the more logical target.

What the study does not show

It is worth being clear about the limits.

• •It was done in mice. Mouse and human sensory systems are similar in many respects, but findings in animals do not always carry over to people.
• •It modeled one kind of pain. Prostaglandin E2 creates short-term inflammatory pain. Nerve injury pain, fibromyalgia, migraine and other chronic pain conditions may work differently.
• •It is basic science, not a treatment. No new drug or therapy came out of this study. Turning mechanisms into medicines typically takes many years and many further studies.

The study is best read as an important piece of a map, not a destination.

What this means if you live with pain

For anyone whose pain has been doubted, the research carries a quieter message. Warmth that burns and touch that hurts are not imagined or exaggerated. They reflect measurable changes in how the nervous system is signaling, even when nothing looks damaged from the outside.

It also underlines why persistent or unexplained pain deserves a proper medical assessment. See a doctor promptly if pain is new and severe, keeps getting worse, comes with fever, redness or swelling that could signal infection, or comes with numbness, weakness or changes in bladder or bowel control.

Many people with long-term pain also explore complementary approaches, and NCCIH funds research on them. For chronic low back pain, the American College of Physicians' 2017 guideline recommends starting with non-drug options, including exercise, tai chi, yoga, acupuncture and mindfulness-based stress reduction, while noting that the benefits are generally modest. These approaches were not part of this study, and there is no evidence yet that they act on the specific mechanisms it describes. The most useful path is usually one where complementary care sits alongside medical care, with your clinicians aware of everything you are using.