Researchers at the University of Minnesota are planning to explore everything from experimental new medications to exercise regimens to see if they can reverse the genetic triggers that predispose people to chronic and severe low back pain.

A new $3.2 million federal grant is kickstarting the research, which will map out genes linked to back pain and explore whether they can be tweaked in ways that decrease discomfort and prevent acute episodes from becoming chronic. Back-pain sufferers are in dire need of options because surgeries offer mixed results and opioid painkillers run the risks of dependency and addiction, said Laura Stone, a U professor who is leading the research.

"We're horrible at this," she said. "Some treatments work for some people, but how do we know who is going to benefit from what? It's pretty bad. My own partner has back pain, and I'm an expert in back pain and I have nothing to help him, except [telling him to] stay active."

A key goal is preventing the dull aches or sharp stings that follow accidents or injuries from becoming chronic back pains that persist for 12 or more weeks. Chronic pain takes an immense physical and emotional toll on patients, and also increases medical spending and decreases worker productivity. One in 12 U.S. adults have chronic back pain they characterize as "severe," and 60% have workplace limitations as a result, a 2022 study estimated.

No conditions have contributed to rising U.S. health care spending more than neck and low back pain combined, according to a 2020 analysis by the Institute for Healthcare Metrics and Evaluation in Washington state. At $134 billion, spending on these conditions made up 4% of the total U.S. health care bill in 2016 and exceeded spending on diabetes, heart disease and cancer, the analysis showed.

Chronic low back pain is more common among women, the elderly and people who live in poverty and can't afford the fitness opportunities or treatments that can keep an acute injury from worsening. Stone found that back-pain risks can vary by the actions of genes, the inherited coding in the body that sets a person's physical characteristics, and how a person's lifestyle and environment interact with those genes.

Stone conducted research at McGill University in Quebec a decade ago that linked the expression of one gene to back pain, which occurred when spinal discs fractured or slipped out of place. Decreased expression of certain proteins by that gene coincided with back pain, perhaps by sending signals to the body that increased swelling made nerves more sensitive. Her team then found that a chemical process called DNA methylation changed that expression level, which in turn could make people more resilient to back pain and disc problems.

"It doesn't change the genetic code, but it can turn the volume up or down on different genes," she said. "We have several mechanisms for adjusting that volume."

In reality, the expression levels of multiple genes likely play roles in spinal injuries and back pain, Stone said. Advanced technology at the U's Genomics Center will allow her research team to identify the roles that all genes play in this process, and whether DNA methylation can modify their expression levels.

The next step will be to test different methods of DNA methylation, including new experimental medications and existing cancer drugs Stone said have potential, to see if they reduce or prevent chronic back pain.

Stone described one animal test that could demonstrate whether these therapies work before they are tried in clinical trials on back-pain sufferers. Mice are exposed to acetone, a chemical that creates a cooling sensation on their skin. Those simulated to have disc degeneration should react more dramatically than those that have been medicated to reduce their pain levels.

"It's a really low-tech test, but it's one of my favorites," Stone said.

New drugs will need to be scrutinized, she said, because they could change genetic expression in ways that reduce back pain but have other unintended effects. Existing medications with known safety profiles could offer faster treatments, along with supplements already on the market and even exercise regimens that are known to coax DNA methylation.

Genes are fairly hard-wired, but genetic expression is "plastic" and can be influenced by medications, diet and lifestyle habits, she said: "It will respond to changes in your environment or your lifestyle."

One planned U study will use imaging scans to see if mice that exercise more on a treadmill have less degeneration in their spinal discs.

Another will examine an over-the-counter supplement called SAM-e that already is marketed as a solution for joint pain. Stone said its claims are largely untested, but it could affect genetic expression and resulting back pains.

Mapping out the key genetic activities will unlock many such studies, she said: "We need to take this to a clinical population and look at the effects of exercise or some of these [genetic expression modifying] drugs in patients, but we need to do this foundational stuff first."