Scientists have long thought that an overly sensitive nervous system is the culprit behind chronic pain. But how and why does it stay so sensitive over time? In a recent study published in Cell Reports, researchers at King’s College London think they might have found an answer, or at least the beginning of one: Some of the long-term changes that occur with a painful insult appear to be recorded at the molecular level and preserved in some immune-cell genes.
“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,” lead author Franziska Denk said in a news release. “We want to know why these proteins and channels should maintain their altered function over such a long period of time.”
Normally, the majority of proteins in the brain have a half-life of less than 14 days. Yet in a mouse model of chronic neuropathic pain, Denk and her colleagues found that certain crucial proteins were “being replaced by malfunctioning versions of themselves,” according to the researchers.
The scientists hypothesize that the problem is not with the genome but rather the epigenome, the molecular signals that essentially turn certain genes on or off. Denk’s team thinks the key is a certain kind of genetic material called an enhancer, specifically a kind of enhancer associated with cells called microglia, which are the central nervous system’s main immune defense. In the case of chronic pain, those microglia undergo changes that persist over time, according to the authors, “in effect functioning as a molecular footprint of prior events.”
“Our data provide evidence that peripheral nerve injury changes the landscape of microglial enhancers — a process that could maintain these cells in an abnormal, maladaptive state,” the scientists report.
Denk says the study is just the first step toward trying to understand why and how such maladaptive molecular footprints affect the function of proteins, as well as whether they’re ultimately the reason chronic pain persists so long.
The need for answers has never been greater. Close to 30 percent of all American adults suffer from some sort of severe or chronic pain, according to a 2012 National Institutes of Health study, with a cost to the federal government of approximately $250 billion a year.