Are some anti-inflammatories a springboard to chronic pain?


Are some anti-inflammatories a stepping stone to chronic pain?

Anti-inflammatories are very effective painkillers.

Remedies to non-steroidal anti-inflammatory analgesics, such as Advil or Motrin, commonly used to treat acute pain such as back pain, would increase the risk of onset of chronic pain, Quebec researchers have found.

This observation is the result of chance. Bioinformatician Marc Parisien and his colleagues at McGill University were trying to better understand the mechanisms involved in the onset of pain when they made a discovery that seemed to upset the traditional conception of the treatment of acute pain.

The Montreal team followed 98 people who attended a pain management clinic to treat acute back pain. She took blood samples from these patients during their first appointments and then three months later, with the aim of comparing their genetic information. The researchers' objective was to compare the data of those whose lower back pain resolved with that of patients whose pain became chronic.

“It's kind of like taking inventory of what's going on in their blood over time. What will be different between people who heal quickly and those in whom it stretches? »

—Marc Parisien

What the researcher and his collaborators found came as a surprise. All the analyzes led us to neutrophils, notes Mr. Parisien. Neutrophils are white blood cells involved in the body's defense against bacterial infections, but they are also present in the early stages of acute inflammation.

“Changes in gene expression were observed in subjects whose pain resolved between the two appointments, showing that neutrophils also play a key role in pain resolution. »

—  Marc Parisien

The rapid regulation of inflammatory responses by neutrophils seems to protect against the transition to chronic pain, continues the researcher.

  • Acetylsalicylic acid (Aspirin)
  • Celecoxib (Celebrex)
  • Diclofenac (Voltaren)
  • Ibuprofen (Advil and Motrin)
  • Indomethacin (Indocid)
  • Meloxicam (Mobic and Vivlodex)
  • Naproxen (Aleve)

This discovery led the team to modulate neutrophil levels in groups of rodents that underwent the same surgery to verify the effects of these cells on pain control.

These experiments showed that blocking the action of neutrophils prolongs over time up to ten times the pain felt by mice.

One group of mice received early treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief. The soothing effects of anti-inflammatories have been observed on acute postoperative pain. So these drugs protect against pain, but the suffering was prolonged over time, notes Marc Parisien.

This observation has not been observed with other analgesics such as acetaminophen (Tylenol) or opioids (codeine, morphine and oxycodone).

“You still have to be careful because while mice have an immune system similar to humans, it is not identical. And humans have a lot more neutrophils in their blood than mice. »

—Marc Parisien

Armed with these results obtained in rodents, the McGill team returned to verify their results in a larger number of humans. She conducted an analysis of the records of the 500,000 people participating in the UK Biobank, a biomedical and genetic database built up over 20 years in the United Kingdom.

This analysis shows that participants who took NSAIDs for pain are more likely to experience chronic pain two to ten years later.

Again, this effect was not seen in people taking acetaminophen or other pain relievers.

For Dr. Anne-Marie Pinard, chronic pain anesthesiologist and professor at Laval University, all these results are very interesting, even if they remain in the field of basic research for the moment.

“The idea that blocking inflammation may interfere with pain healing is not entirely new, but the way of which they bring it up with such striking evidence is interesting. »

— Anne-Marie Pinard

Dr. Pinard believes that these results should be modulated. What the study with the patient bank shows is an association. We have not pointed clearly, clearly and precisely to a cause and effect relationship.

Marc Parisien and his colleagues recognize the limits of their work.

“Our evidence remains circumstantial. Ideally, it should be verified in other cohorts, for example with the Quebec database CARTaGENE and by randomized double-blind clinical trials. »

— Marc Parisien

The authors thus recognize that other work must be carried out to confirm their findings, which call into question, more or less, conventional attenuation treatments. pain.

You have to weigh the trade-off between treating the intensity of acute pain versus that of chronic pain, says Parisien, adding that sometimes a short-term solution can cause long-term problems.

< p class="e-p">The publication of this work created a small commotion in the world of pain treatment.

This study is super interesting because it opens the way to a reflection, particularly for health professionals, says Pre Pinard.

“We often think that absolutely nothing should hurt in life. I'm not saying you have to endure extreme pain, but sharp pain is a useful signal from the body to take a break, not to step on your foot or dance when your back hurts. […] The body does things right when you let it, it creates an inflammatory response to heal. »

—Anne-Marie Pinard

Now, do we have to throw anti-inflammatories in the trash? No. It shows us, however, that inflammation is necessary for the healing process, she adds.

A widespread disease

  • Data collected by Statistics Canada shows that nearly 8 million Canadians live with chronic pain.
  • Acute low back pain is defined as pain experienced for six weeks or less.
  • Chronic low back pain is described as a deep, throbbing, dull or burning pain localized in the lower back or radiating down the leg that lasts for more than three months.

M. Parisien evokes the idea of ​​rescue to perfect or develop new drugs to counter the harmful effects of current NSAIDs.

“We could preserve the x27;Effect of acute pain reduction of anti-inflammatories by masking the effect of prolonging pain through a protein complex. »

— Marc Parisien

To this end, the study also made it possible to establish that the injection of a complex of proteins (S100A8/A9) normally released by neutrophils prevented the development of long-lasting pain induced by an anti-inflammatory drug.

The detail of this work is published in the journal Science Translational Medicine.


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