There’s a medical principle that goes back to the early 16th century: Dosis sola facit venenum – in modern language, you may know it as “only the dose makes the poison”. It’s the idea that, in the right quantity, anything can be harmful, even everyday medicines.
A new study, published in the journal Science Translational Medicine, has proven this maxim true for one of our most familiar painkillers. According to the paper, anti-inflammatory drugs – a group including first-aid mainstays like Advil (a brand name for ibuprofen) and aspirin – can increase patients’ chances of developing chronic pain.
“For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs,” said study co-author Jeffrey Mogil, a Professor in the Department of Psychology at McGill University and E. P. Taylor Chair in Pain Studies.
“But we found that this short-term fix could lead to longer-term problems,” he explained.
Supporting this conclusion is data from 128 human participants and some mice – and unusually for experiments exploring drug effects, the humans came first.
To start with, the researchers enrolled 98 people being treated for lower back pain with anti-inflammatories over three months. They wanted to investigate the mechanisms of pain, and how exactly these drugs affect them, so they chose two equally sized groups – one made up of people whose pain cleared up over the experiment schedule, and one of the people whose pain persisted – and performed genome analysis on them.
What they found was an observable difference between people who recovered from pain and those who didn’t – and it all came down to a type of white blood cell called neutrophils.
“Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage,” explained Mogil. Patients who recovered were found to have much more extreme levels of these cells over the course of the treatment period: very high at the start, compared to the non-recovered group, with a steeper drop-off by the end of the three months.
The researchers decided to probe the idea further by recruiting 30 people with temporomandibular disorder, a painful condition affecting the muscles around your jaw and ears. The results “replicated our finding,” the researchers wrote – confirming that neutrophils are important for pain recovery.
But to learn just how important these cells are, the researchers needed the help of some rodent participants. In mouse experiments, the team found that blocking neutrophils could extend pain duration up to ten times – and that administering anti-inflammatory drugs extended it to twice as long as giving no treatment.
The researchers even administered other pain relief drugs, to check it was the anti-inflammatory properties and not simply the analgesic effect that was causing the longer pain experience. It just confirmed their hypothesis: anti-inflammatories seem to uniquely extend pain – even if they’re effective pain relievers in the short term.
“Inflammation occurs for a reason,” Mogil said. “It looks like it’s dangerous to interfere with it.”
But do these experiments – plus the study’s finding that subjects from the 500,000-participant strong UK Biobank resource were more likely to have pain two to ten years later if they treated initial aches with anti-inflammatories versus other drugs – mean that we should rethink reaching for the ibuprofen next time we feel a twinge? Maybe not yet, researchers say.
“This study is a wonderful start to providing an answer to this question, but it now needs to be replicated and further investigated by other scientists,” said neuroimmunologist Franziska Denk, a senior lecturer at King’s College London, who was not involved in the study.
“It would most definitely be premature to make any recommendations regarding people’s medication until we have results of a prospectively designed clinical trial,” she explained. “In my opinion, this study should not generate a debate around the use of NSAIDs in low back pain – much more research is needed to confirm these findings first.”
Nevertheless, the findings are “very intriguing,” she added – and the team responsible hope that it may prompt further study into other pain management methods.
“We discovered that pain resolution is actually an active biological process,” explained study co-author Luda Diatchenko, a Professor in the Faculty of Medicine, Faculty of Dentistry, and Canada Excellence Research Chair in Human Pain Genetics
“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.”