Anti-Inflammatory Drugs Could Cause Chronic Pain

New research from McGill University reveals blocking inflammation may lead to chronic pain.

Findings may change how we treat acute pain

Whenever you have a headache, your back hurts, your arthritis flares up, or you have a fever, odds are you will be taking some anti-inflammatory medicine. NSAIDs, or nonsteroidal anti-inflammatory drugs, are the most prevalent form of anti-inflammatory medication. According to the American Gastroenterological Association, nearly 30 million Americans take them every day to ease pain or discomfort.

The most common types of NSAIDs include aspirin, ibuprofen (commonly referred to as Advil), and naproxen (known by the brand name Aleve and Naprosyn). However, despite their popularity, these medicines can have side effects.

According to McGill University and colleagues in Italy, using anti-inflammatory drugs and steroids to treat pain may increase the risk of developing chronic pain. Their findings call into question traditional pain-relief methods. Normal recovery from a severe injury involves inflammation, and medicines that prevent that inflammation may result in more difficult-to-treat pain.

“For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs. But we found that this short-term fix could lead to longer-term problems,” says Jeffrey Mogil, a Professor in the Department of Psychology at McGill University and E. P. Taylor Chair in Pain Studies.

The difference between people who get better and don’t

In the study published on May 11th, 2022 in Science Translational Medicine, the researchers examined the mechanisms of pain in both humans and mice. They found that neutrophils – a type of white blood cell that helps the body fight infection – play a key role in resolving pain.

“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away. Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils,” says Luda Diatchenko a Professor in the Faculty of Medicine, Faculty of Dentistry, and Canada Excellence Research Chair in Human Pain Genetics.

Inflammation plays a key role in resolving pain

“Neutrophils dominate the early stages of inflammation and set the stage for the repair of tissue damage. Inflammation occurs for a reason, and it looks like it’s dangerous to interfere with it,” says Professor Mogil, who is also a member of the Alan Edwards Centre for Research on Pain along with Professor Diatchenko.

Blocking neutrophils in mice increased pain duration by up to tenfold. Anti-inflammatory medicines and steroids such as dexamethasone and diclofenac had the same effect, despite being helpful against pain early on.

These results are also corroborated by a separate study of 500,000 individuals in the United Kingdom, which found that those who used anti-inflammatory medicines to alleviate their pain were more likely to have pain two to ten years later, an effect not observed in people who took acetaminophen or anti-depressants.

Reconsidering standard medical treatment of acute pain

“Our findings suggest it may be time to reconsider the way we treat acute pain. Luckily pain can be killed in other ways that don’t involve interfering with inflammation,” says Massimo Allegri, a Physician at the Policlinico of Monza Hospital in Italy and Ensemble Hospitalier de la Cote in Switzerland.

“We discovered that pain resolution is actually an active biological process,” says Professor Diatchenko. These findings should be followed up by clinical trials directly comparing anti-inflammatory drugs to other pain killers that relieve aches and pains but don’t disrupt inflammation.”

Reference: “Acute inflammatory response via neutrophil activation protects against the development of chronic pain” by Marc Parisien, Lucas V. Lima, Concetta Dagostino, Nehme El-Hachem, Gillian L. Drury, Audrey V. Grant, Jonathan Huising, Vivek Verma, Carolina B. Meloto, Jaqueline R. Silva, Gabrielle G. S. Dutra, Teodora Markova, Hong Dang, Philippe A. Tessier, Gary D. Slade, Andrea G. Nackley, Nader Ghasemlou, Jeffrey S. Mogil, Massimo Allegri and Luda Diatchenko, 11 May 2022, Science Translational Medicine.
DOI: 10.1126/scitranslmed.abj9954