Summary: Anti-inflammatories may relieve pain in the short term, but blocking inflammation can lead to longer-term chronic pain, a new study reports.
Source: McGill University
Using anti-inflammatory drugs and steroids to relieve pain could increase the chances of developing chronic pain, according to researchers from McGill University and colleagues in Italy.
Their research puts into question conventional practices used to alleviate pain. Normal recovery from a painful injury involves inflammation and blocking that inflammation with drugs could lead to harder-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 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 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.
Experimentally blocking neutrophils in mice prolonged the pain up to ten times the normal duration. Treating the pain with anti-inflammatory drugs and steroids like dexamethasone and diclofenac also produced the same result, although they were effective against pain early on.
These findings are also supported by a separate analysis of 500,000 people in the United Kingdom that showed that those taking anti-inflammatory drugs to treat their pain were more likely to have pain two to ten years later, an effect not seen in people taking 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.”
“Acute inflammatory response via neutrophil activation protects against the development of chronic pain” by Marc Parisien et al. was published in Science Translational Medicine.
Acute inflammatory response via neutrophil activation protects against the development of chronic pain
The transition from acute to chronic pain is critically important but not well understood.
Here, we investigated the pathophysiological mechanisms underlying the transition from acute to chronic low back pain (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with acute LBP, followed for 3 months.
Transcriptomic changes were compared between patients whose LBP was resolved at 3 months with those whose LBP persisted. We found thousands of dynamic transcriptional changes over 3 months in LBP participants with resolved pain but none in those with persistent pain.
Transient neutrophil-driven up-regulation of inflammatory responses was protective against the transition to chronic pain. In mouse pain assays, early treatment with a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led to prolonged pain despite being analgesic in the short term; such a prolongation was not observed with other analgesics.
Depletion of neutrophils delayed resolution of pain in mice, whereas peripheral injection of neutrophils themselves, or S100A8/A9 proteins normally released by neutrophils, prevented the development of long-lasting pain induced by an anti-inflammatory drug.
Analysis of pain trajectories of human subjects reporting acute back pain in the UK Biobank identified elevated risk of pain persistence for subjects taking NSAIDs.
Thus, despite analgesic efficacy at early time points, the management of acute inflammation may be counterproductive for long-term outcomes of LBP sufferers.