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McGill study finds anti-inflammatory drugs may lead to chronic pain

Pain is one of the most common reasons why people seek medical attention. The most popular medications people reach for when experiencing pain are anti-inflammatory drugs, such as ibuprofen—also known as Advil. But according to a new study led by Dr. Luda Diatchenko, a renowned pain researcher and professor of medicine and dentistry at McGill, these drugs may actually prevent pain resolution and promote the development of chronic pain

Diatchenko’s study aimed to better understand the underlying biological mechanisms associated with chronic pain development. The team of researchers recruited 98 patients with lower back pain for the study. The patients were divided into two groups: Those whose pain was resolved within three months of their first visit, and those whose pain persisted, and was therefore considered “chronic”.

To gain insight into which mechanisms are causing persistent pain, Diatchenko’s team analyzed the gene expression of the participants. Knowing which genes are differentially expressed between the two groups would allow the researchers to know what mechanisms—the researchers look at any and all mechanisms to avoid bias—are activated in one group and not the other. Diatchenko and her team hoped to find unique mechanisms that were active in the patients whose pain persisted, and that these mechanisms would therefore potentially be responsible for the development of chronic pain. 

“We expected that something was happening in the patients whose pain persisted […] but it was actually the opposite,” Diatchenko said in an interview with The McGill Tribune

What they found instead was a mechanism that was much more active in the group of patients whose pain resolved—and this process was inflammation. The results showed that during the phase of acute pain, up to a few days after the injury, genes associated with inflammation were more highly expressed in patients whose pain resolved, compared to patients whose pain persisted. This led to the scientists hypothesizing that inflammation during early pain stages protects against the development of chronic pain. 

The team then ran several experiments to test this new idea. They induced pain in mice and treated them with five different types of drugs. Two of them had anti-inflammatory properties while the other three only had analgesic, or pain-reducing, properties. All five drugs were effective at reducing pain in the short term. However, only the mice that were administered the anti-inflammatories developed chronic pain.  

In fact, anti-inflammatory drugs, such as ibuprofen, inhibit the inflammatory process, which consequently reduces pain. On the other hand, analgesic drugs with no anti-inflammatory properties, such as acetaminophen, also known as Tylenol, do not interfere with inflammation. 

The researchers’ findings suggest that inflammation following an injury allows proper healing to take place, which prevents the prolongation of pain. When people use anti-inflammatory drugs to provide relief, it interferes with this healing process. Although pain will be reduced in the short term, the development of chronic pain becomes more likely. 

“For acute pain, this study would very much suggest that Tylenol is a better idea than Advil,” said Jeffrey Mogil, a senior author of the study and E.P. Taylor Professor in Pain Studies at McGill, in an interview with the Tribune.

The final part of the study consisted of analyzing data from a large cohort of patients with acute lower back pain. Diatchenko and her team found that the biggest predictor of whether the pain would persist or be resolved was the use of anti-inflammatories.

“People who used [anti-inflammatory drugs] at acute back pain stages had a 1.7 times higher probability of having chronic pain two to 10 years later,” said Diatchenko.

Diatchenko and her team’s findings have garnered international attention, as it is the first study ever to show that anti-inflammatory drugs play a role in the development of chronic pain. However, the authors emphasize that no medical advice can be given based on this study alone as no clinical trials have been conducted yet. It is important to conduct diligent randomized controlled trials, especially when the findings of this study are challenging centuries of medical practice. 

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