When pain isn’t the same for everyone

Not all pain is the same – but it is often treated as if it were. Biologist Manuela Schmidt intends to change that. She investigates tiny nerve cells to find what distinguishes a child’s pain from that of an adult. By now, she has identified significant molecular differences. This could pave the way for a more targeted treatment of chronic pain in the future.

Biology and Medicine

by Anna Stockhammer

July 6, 2026

A child experiences pain differently from an adult; a woman differently from a man; an 80-year-old differently from a 17-year-old. And yet they are often prescribed the same pill, the same therapy. This is precisely where one of the most persistent problems in modern medicine resides.

“For a long time, it was a major limitation in this field that we treated everyone the same,” says Manuela Schmidt. Schmidt, a biologist and pharmacologist from the University of Vienna, is in charge of the FWF-funded research project “Pediatric chronic pain – proteome-based systems biology”. Schmidt is investigating why pain does not develop in the same way in all people – and what role age and gender play in this process at the molecular level.

Around 1.5 million people in Austria live with chronic pain. It informs the lives of those affected for months or years – physically, psychologically, and socially. Treatments often reach their limits: they don’t work for everyone, trigger side effects, and are rarely tailored to the individual. Schmidt wants to change that.

Pain Research

Chronic pain is often difficult to treat effectively. One challenge in modern medicine is that the same therapies are typically used for all patients. To identify new targets for more effective treatments, researchers in Vienna are investigating how age and sex influence the development of pain.

The hot stove and a preemie

Schmidt’s path to pain research began with a very everyday image: a hand reaching for a hot stove burner. The body perceives such stimuli – heat, pressure, corrosive substances – via very delicate sensors in the skin. As a post-doctoral researcher, Schmidt investigated tiny molecular detectors in the fingertips, known as TRP channels. They sense heat. They sense acid. They sound the alarm. But over the years, Schmidt began to focus her research on something else: not the brief, sharp pain, but the pain that lingers.

Schmidt also became more attuned to the issue through a personal experience. Her son was born extremely prematurely and had to endure numerous painful treatments after birth. While he is now, fortunately, a healthy schoolboy in Vienna, the experience made her reflect on how little is known about pain in babies, children, and adolescents. “Especially when it comes to those who are most vulnerable, we know almost nothing about how chronic pain is processed at the molecular level – and how that differs from the typical adult male, who is still considered as the standard in clinical studies,” says Schmidt.

Where pain begins

Whilst pain registers in the brain, it begins elsewhere. Schmidt focuses on the nerve cells that transmit signals from the skin, muscles, and organs to the spinal cord and brain. The messages these nerve cells send help determine whether acute pain becomes chronic. Schmidt calls these cells the “drivers” – and thus also potential targets for new therapies.

In concrete terms, Schmidt’s team is examining small nerve clusters located directly next to the spinal cord, known as the dorsal root ganglia. This is where the cell bodies of the peripheral nerves sit, whose extensions reach all the way to the fingertips. The study compares male and female mice as well as adolescent animals and young adults – using an established model for neural pain.

Graphical representation of an analysis of proteins altered by nerve injury — The analysis of proteins altered by nerve injury reveals different changes depending on age and sex over periods of 7, 14, and 98 days. The overlaps, which show how the proteins change in general, also represent an important starting point for research. © Sabrina Grundtner et al., 2025

Proteins instead of just genes

What makes this project unique is that Schmidt and her team are looking at the proteins themselves, not just the genetic blueprints behind them. Many studies measure mRNA – i.e., which genetic information is being read in the cell. But that doesn’t reveal which protein is actually produced in the end, or how much of it. Especially in the case of chronic pain, mRNA can be misleading.

“The protein is the active component in the cell,” says Schmidt. It can be the channel that opens when encountering heat, or a switch in an inflammatory process. Her team has developed a particularly sensitive method for this purpose that can produce reliable analyses of even the smallest tissue samples.

Differences that no one had seen before

The findings so far demonstrate just how important this closer inspection is: the team found clear differences between age groups, between early and late pain phases, and between male and female animals.

This becomes particularly clear when comparing adolescent and adult mice. At the protein level, differences were evident both shortly after a nerve injury and in later phases, up to three months later. Adolescence, in particular, is a sensitive phase in development because significant biological remodeling processes are still underway in the body. The data suggest that adolescents are not simply “small adults.” Their pain processing follows molecular programs that are partly different from those of adult animals. For pain research, this means that age must be given greater consideration as a biological variable – also with a view toward more precise therapeutic approaches in the long term.

Another example is the interaction between nerve cells and immune cells. It was already known that there can be gender differences between immune processes in case of pain. Schmidt’s project now gives more detailed insights into which protein networks are involved and which programs are activated in the participating immune cells.

The chronology also plays an important role. Immediately after a nerve injury, there is a primary focus on inflammatory processes. Later on, there is an onset of processes that are more indicative of regeneration. Because Schmidt’s team has tracked this development over a longer period than many previous studies, they have found a more nuanced picture of how chronic pain develops, changes, and persists.

Data for others to build upon

The goal of the project is not to develop a drug ready for use. Instead, it provides a foundation that other researchers can build upon. The data is publicly accessible so that colleagues worldwide can specifically search for relevant proteins and plan their experiments in a better way.

For Schmidt, this also tallies with the so-called 3R principles in animal research: if comprehensive data is already available, unnecessary experiments can be avoided. At the same time, she emphasizes the limitations of such models. “A mouse is not a human, but it is our model,” says Schmidt. For her, it is key to keep in mind who the patients are in the end.

In the long term, the project fits into a broader goal of medicine: not only should therapies be effective in general, they should also be more closely tailored to specific patient groups – Taking account of age, gender, the stage of pain, and molecular mechanisms. According to Schmidt, there is still a long way to go, but the direction is clear. “The project is a first attempt, a first jab to hopefully gather momentum.” The message behind it is simple: pain is not the same for everyone. Anyone who wants to understand and treat it must take a closer look – all the way down to the level of proteins.

About the researcher

Manuela Schmidt is a biologist and pharmacologist at the University of Vienna. Her work focuses on the molecular mechanisms of chronic pain and sensory nerve cells in the peripheral nervous system, as well as on how age and gender influence pain processes. In the project “Pediatric chronic pain – proteome-based systems biology” (2022–2026), funded by the Austrian Science Fund (FWF) with EUR 67,000, she uses high-resolution proteomics to investigate differences in neuropathic pain in children as compared to adults. In March 2026, Schmidt was awarded the Weiss Prize, a privately funded research prize that is awarded once a year by the FWF’s alpha+ Foundation.