If you haven’t had the misfortune to experience it yourself, you probably know someone who deals with chronic pain. Whether it stems from a sports injury, surgery, or some kind of accident, pain that lingers long after an incident is common. Yet despite its ubiquity, researchers still aren’t sure why chronic pain occurs, so patients are left to suffer with only temporary relief like painkillers, among other options. A new study from King’s College London, however, provides the groundwork for an explanation behind this kind of pain.

Regardless of what caused it, chronic pain results in an oversensitive nervous system, which responds and causes pain more than it normally would. Why the nervous system would remain so touchy over a long period is a mystery, especially when the initial injury or illness has healed. To tackle this question, researchers looked at the immune cells in the nervous systems of mice because they are known to be involved in generating persistent pain.

The team discovered that nerve damage, which occurs in the event of an accidental injury or disease, can change epigenetic marks on certain genes in immune cells. (Epigenetics is concerned with how genes are expressed and where.) Some epigenetic markers have a direct effect on the person, while others mark potential effects, signaling that a cell could act or be modified in the future. During the study, the researchers came across cells that behaved normally but had epigenetic marks that suggested they carry a “memory” of the initial injury. This recall could be the reason for seemingly random bouts of pain.

“We are ultimately trying to reveal why pain can turn into a chronic condition,” said Dr. Franziska Denk, first author of the study from King’s College London, in a press release. “We already knew that chronic pain patients have nerves that are more active, and we think this is probably due to various proteins and channels in those nerves having different properties.”

Denk explained that it’s still unclear why the nerves remain so sensitive, and the researchers wanted to know why these specific proteins and channels would stay altered over a long time.

“Cells have housekeeping systems by which the majority of their content are replaced and renewed every few weeks and months — so why do crucial proteins keep being replaced by malfunctioning versions of themselves?” Denk said. “Our study is the very first step toward trying to answer this question by exploring the possibility that changes in chronic pain may persist because of epigenetics.

Denk added that future research into the problem could help in the development of new therapeutics. Dr. Giovanna Lalli, Neuroscience & Mental Health Senior Portfolio Developer at the Wellcome Trust, which co-funded the study, echoed this sentiment.

“People develop chronic pain for a huge variety of reasons. We therefore need an equally diverse range of treatments to tackle the different root causes,” she said. “The clues from this study, suggesting epigenetic changes may be involved in pain persisting, will hopefully lead us to better understand the mechanisms underlying chronic pain.”

Source: Denk F, et al. Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain. Cell Reports. 2016.