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HomeA FocusIbuprofen may worsen some chronic pain and increase risk of kidney injury...

Ibuprofen may worsen some chronic pain and increase risk of kidney injury in BP patients

Ibuprofen, one of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) in use, may be contra-indicated in some conditions where it has long been used, writes MedicalBrief. Recent research cautions on use in pain management and in combination with certain blood pressure medications.

A preliminary Canadian study – carried out by a team from McGill University, Canada, and colleagues in Italy – and released this week, recommends further research into a possible link between NSAID and longer-term problems like back pain, say researchers. Their preliminary findings suggest that drugs like ibuprofen and steroids, used to relieve short-term health problems, might possibly increase the chances of developing chronic pain.

Their research comes on the heels of another recently published Canadian study from the University of Waterloo, warning that people taking a diuretic and a renin-angiotensin system (RSA) inhibitor for high blood pressure should be cautious about also taking ibuprofen, because of the possibility of acute kidney failure, which in some cases can be permanent.

The Guardian writes that the results from the small McGill study indicate that it could be time to reconsider how pain is treated. Normal recovery from a painful injury involves inflammation, the body’s natural reaction to injury and infection, and this latest research suggests blocking inflammation with drugs could lead to harder-to-treat issues.

The study’s authors said it could be that inflammation has a protective effect, such as preventing acute pain from becoming chronic, and that overly reducing it may be harmful. Their findings were published in Science Translational Medicine.

The authors of the Waterloo study, which appeared in Mathematical Biosciences, noted that diuretics and RSA inhibitors were commonly prescribed together for people with hypertension and were available under various pharmaceutical brand names. Painkillers such as ibuprofen are available over-the-counter and in people with certain medical profiles, the combination can cause acute kidney injury, which in some cases can be permanent.

In the McGill study, Jeffrey Mogil, a professor of pain studies at McGill, said: “While ibuprofen was not studied explicitly in either the human or the mouse data (in the mouse we used diclofenac), as ibuprofen is so common in the UK, it is highly likely that a large percentage of those in the UK Biobank who reported taking ‘NSAIDs’ were in fact taking ibuprofen.”

Researchers said the findings were supported by a separate analysis of 500,000 people in the UK Biobank study, which showed that those taking anti-inflammatory drugs were more likely to have pain two to 10 years later. This effect was not seen in people taking paracetamol or anti-depressants.

Researchers said lower-back pain was the most commonly reported form of chronic pain – pain that persists for longer than would be expected after the injury – and resulted in massive economic and medical costs each year.

Most patients receive standard treatments such as non-steroidal anti-inflammatory drugs like ibuprofen and corticosteroids. But these drugs are only somewhat effective, and little is known about why acute pain, which begins suddenly in response to something specific, is resolved in some patients but persists as chronic pain in others.

To understand the transition from acute to chronic lower-back pain, researchers followed 98 patients with acute lower-back pain for three months. They also examined the mechanisms of pain in both humans and mice, and found that neutrophils – a type of white blood cell that helps the body fight infection – play a key role in resolving pain.

Blocking these cells in mice prolonged the pain for up to 10 times the normal duration, Treatment with anti-inflammatory drugs and steroids such as dexamethasone and diclofenac also produced the same result, although they were effective against pain early on.

Prof Blair Smith, from the University of Dundee, said: “The theory is that inflammation may have a protective effect in the long-term, and that overly reducing inflammation may be harmful. “However, it is important to note that this is just one study, and more research is needed to confirm and investigate this further.”

Study details

Acute inflammatory response via neutrophil activation protects against the development of chronic pain

Marc Parisien, Lucas Lima, Concetta Dagostino, Nehme El-Hachem, Gillian Drury, Audrey V. Grant, Jonathan Huising, Vivek Verma, Carolina Meloto, Jaqueline Silva, Gabrielle Dutra, Teodora Markova, Hong Dang, Philippe Tessier, Gary Slade, Andrea Nackley, Nader Ghasemlou, Jeffrey Mogil, Massimo Allegri, Luda Diatchenko.

Published in Science Translational Medicine on 11 May 2022

Abstract
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 three months. Transcriptomic changes were compared between patients whose LBP was resolved at three months with those whose LBP persisted. We found thousands of dynamic transcriptional changes over three 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.

 

Study details (Waterloo University, Ontario)

Determining risk factors for triple whammy acute kidney injury

Jessica Leete, Carolyn Wang, Francisco López-Hernández, Anita Layton.

Published in Mathematical Biosciences in May 2022

Abstract

Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as “triple whammy”. Diuretics and RAS inhibitors, such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common. The goals of this study are to better understand the mechanisms underlying the development of triple whammy AKI and to identify physiological factors that may increase an individual’s susceptibility. To accomplish these goals, we utilize sex-specific computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that low water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI. Triple treatment involving an ACE inhibitor, furosemide, and NSAID results in blood pressure levels similar to double treatment with ACEI and furosemide. Additionally, the male and female hypertensive models act similarly in most situations, except for the ACE inhibitor and NSAID double treatment.

 

The Guardian article – Short-term use of ibuprofen may increase chance of chronic pain, study suggests (Open access)

 

Mathematical Biosciences article – Determining risk factors for triple whammy acute kidney injury (Open access)

 

Science Translational Medicine article – Acute inflammatory response via neutrophil activation protects against the development of chronic pain (Open access)

 

See more from MedicalBrief archives:

 

Ibuprofen links to increased CVD risk in arthritis patients

 

Ibuprofen may extend life span

 

15% of NSAIDs’ users exceed maximum recommended dosage

 

 

 

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