Early Inflammation Protects Against Chronic Pain

Acute pain may turn into chronic pain if early inflammation is interrupted by anti-inflammatory drugs, study suggests.

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With an injury, it is all too common to reach for the anti-inflammatory medications for humans and animals to provide immediate comfort. The objective is sensible—reduce inflammation, pain, and swelling to jump-start the healing process.

However, a recent study has identified that acute pain can turn into chronic pain particularly when early inflammation is interrupted by anti-inflammatory drugs. [Parisien M, Lima LV, Dagostino C, et al. Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Science Translational Medicine May 2022, vol. 14, Issue 644; DOI: 10.1126/scitranslmed.abj9954]

The study revealed that neutrophil activation-dependent inflammation genes are up-regulated in patients with pain that resolves. Those with persistent pain did not experience such gene up-regulation. Studies with rodents demonstrated that treatment with anti-inflammatory medications ended up prolonging the duration of pain yet this receded with administration of neutrophils. Release of S100A8/A9 proteins from neutrophils has a role in mitigating development of chronic pain, but this does not occur when the patient is treated early on with an anti-inflammatory drug.

Findings by researchers looking at results in humans identified that people who recovered from acute pain incidents experienced an initial intense inflammatory response incited by neutrophils migrating to the injury, particularly because they did not take anti-inflammatory medications. This hypothesis was tested on acute pain induced in mice and revealed that treatment with dexamethasone or diclofenac was effective at alleviating pain for the first week, but then pain persisted for a longer duration. This was in stark comparison to pain cessation following treatment with saline or use of pain medications, like acetominophen, that do not affect the inflammatory pathway. These findings were not evaluated for post-operative pain, only for an acute injury.

With this knowledge in mind, perhaps the easy and convenient reach for an NSAID or corticosteroid that impacts the inflammatory cascade is not necessarily the best choice for an injury that could result in a chronic pain condition. 

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