Pain Paradox: How Substance Use May Worsen Chronic Pain
For millions of people living with chronic pain, relief can seem elusive. From injuries to diseases like arthritis and fibromyalgia, chronic pain is defined by discomfort lasting more than three to six months – far beyond a typical recovery period.
As patients search for alternatives to traditional treatments, many are turning to cannabis – and sometimes combining with tobacco – for pain relief. Duke University School of Medicine research relying on national data reveals historically high levels of cannabis use and co-use with tobacco among various age groups from Gen X, ages 18-25, to those over age 50.
However, emerging research suggests that substance use may come with unexpected consequences, including the potential to increase sensitivity to pain.
In recent years, research into the complex relationships between chronic pain, substance use, and addiction has revealed a web of interconnected factors.
A major study led by medical student and clinical researcher Dana Rubenstein, MHS, and F. Joseph McClernon, PhD, professor of psychiatry and behavioral sciences at Duke, examined a bidirectional relationship between cannabis and tobacco use and pain, in which pain can drive substance use, and substance use can worsen pain, a phenomenon long observed in cigarettes, now extended to include cannabis.
Researchers examined data from the 2015-2021 Population Assessment of Tobacco and Health Study, a nationwide sample of U.S. adults, to understand how pain and substance use influence each other.
They learned the co-use of cannabis, also known as marijuana, and tobacco more than doubled the odds of experiencing moderate to severe pain later on compared to using neither of these substances.
Maggie Sweitzer, PhD, a leading researcher in tobacco addiction, has been part of the team investigating how tobacco use affects pain – and the surprising ways in which tobacco use might be making pain worse.
“I’ve always been interested in mechanistic questions,” said Sweitzer, associate professor in the Department of Psychiatry and Behavioral Sciences at Duke School of Medicine. “Why do some people have more difficulty quitting, especially when chronic pain is involved?”
This evolving focus on pain has led Sweitzer to collaborate with other experts, including Katherine Martucci, PhD, a Duke neuroscientist and associate professor of anesthesiology who specializes in human clinical research of chronic pain, to understand the neurological and behavioral effects of smoking and pain perception. “We’ve known for a while that smoking withdrawal increases pain sensitivity,” Sweitzer said. “But we don’t fully understand why.”
This question is at the core of a study Sweitzer is currently working on, examining how nicotine, the main psychoactive ingredient in tobacco products, and pain processing overlap in the brain.
Researchers looked at brain imaging responses to heat-induced pain. Their early findings from the small pilot study have been striking.
“What surprised us was that during nicotine withdrawal, there was less activation in a part of the prefrontal cortex associated with emotion regulation and pain modulation,” she explained.
One interpretation of the results is that essentially nicotine appears to dull the brain’s ability to regulate pain, a finding that underscores the challenge smokers face when trying to quit. Sweitzer is now pushing to expand their research, hoping to replicate these findings with a larger sample.
Working with collaborators, she is also looking at whether people with chronic pain show different brain patterns in response to nicotine withdrawal compared to those without chronic pain.
“This is really the paradox,” she said. “Acute nicotine, short-term seems to have pain-relieving analgesic effects. But long-term, it leads to increased pain response.”
Rubenstein’s research was supported by a NIH-funded pre-doctoral training award to the Duke Clinical and Translational Science Institute. Sweitzer earned a seed grant from the Duke Institute for Brain Sciences to launch her research.
“The research will not only lead to new insights and better treatments for people with chronic pain,” McClernon said. “But also proves the power of internal funding mechanisms for doing early stage research and supporting new collaborations.”
As substance use increases, researchers are focusing on the interconnected risks and challenges individuals face. "This is a call to action for more research and better support for people navigating pain, smoking, and substance use," McClernon said.
Shantell M. Kirkendoll is a senior writer and managing editor in the Office of Strategic Communications.
Photography by Eamon Queeney is assistant director of multimedia and creative in the Office of Strategic Communications.