Longevity

Longevity Briefs: NSAIDs – Short-Term Gain But Long-Term Pain?

Posted on 10 June 2022

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Injuries are followed by a period of pain that usually goes away after the damaged tissue has healed, a process that is orchestrated by the immune system. With increasing age, however, it becomes increasingly common for this short-term pain to persist indefinitely, becoming chronic pain. Chronic lower back pain is the most frequently reported chronic pain condition, and causes more years lived with disability than any other chronic disease. Despite its prevalence, we don’t really understand why short-term pain sometimes becomes chronic pain.

People with lower back pain are often given painkillers like nonsteroidal anti-inflammatory drugs (NSAIDs), which can suppress pain, but do nothing to cure the underlying condition. Improving our understanding of the fundamental biology of chronic pain could help us treat this condition more effectively.

What did the researchers do: In this study, researchers looked at a group of 98 patients who had recently developed lower back pain. They isolated circulating white blood cells from these patients and studied the level of expression of different genes in these cells using a technique called genome-wide transcriptomics. Patients were then followed up 3 months later, which is roughly how long it takes for lower back pain to either resolve or become chronic, and gene expression was analysed again. The researchers’ goal was to see how gene expression varied between patients who had developed chronic pain and patients whose pain had resolved.

Key takeaway(s) from this research: After 3 months, lower back pain was deemed to have been resolved in around half of patients. At the start of the study, there were no significant differences in gene expression between those who would go on to develop chronic pain and those who would not. After 3 months, gene expression hadn’t changed significantly in patients who developed chronic pain, but in those whose pain resolved, there were over 5500 genes with altered levels of activity. Further analysis suggested that most, but not all this change, was due to changes in the abundance of different white cell types.

When the researchers studied these differences in more detail, however, they found something unexpected. Around the time of the first visit, patients whose pain would later resolve had a larger inflammatory response driven by neutrophils, a type of white blood cell known for causing a lot of collateral damage. This inflammation was reduced by the time of the second visit, whereas inflammation in the other group continued steadily. This suggested that a more powerful inflammatory response at the start of the study might actually have protected against chronic pain later on.

The researchers decided to test this possibility in mice. They tested five different painkillers in a mouse model of lower back pain. Unsurprisingly, they all reduced pain in the short term. However, two of the drugs (the steroidal dexamethasone and the NSAID diclofenac) also significantly prolonged the total duration of the painful episode. This appeared to be related to the effects of these drugs on the aforementioned neutrophils, because when the mice were also injected with new neutrophils, these drugs no longer had this effect.

Pain sensitivity following injury in mice treated with either dexamethasone (black squares) or a control (saline, white circles).
Source

The key take-home from this study is that early use of some painkillers, most notably NSAIDs, might actually promote back pain in the long term, as they reduce early neutrophil activity, which seems to be important for preventing short-term pain from becoming chronic. Data from the UK Biobank does suggest an increased risk of pain persistence for subjects taking NSAIDs, but this will need further investigation in controlled human studies.


References

Acute inflammatory response via neutrophil activation protects against the development of chronic pain: https://doi.org/10.1126/scitranslmed.abj9954

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