Do Anti-Inflammatory Drugs, Steroids Cause More Pain Than They Relieve?

Why the drugs you're taking may be hurting you, and what to take instead

I’m no stranger to pain. I’d hazard you probably aren’t either. I had three natural childbirths. But that pain during and after labor paled in comparison to the pain I experienced courtesy of eye cancer.

“Pain is a near-universal experience,” a 2019 systematic review about pain asserts.^[1]

Given that being human sometimes involves being in pain, it make sense that doctors and other healthcare practitioners are always looking for ways to help their patients be pain-free.

As altruistic as that might sound, pain is also a multi-billion-dollar business.

Pharmaceutical companies incentivize doctors to treat pain aggressively in order to maximize their profits. And these companies, along with the physicians who shill for them, have been especially successful at selling addictive opioid pain relievers to the public, creating customers for life.

Big Pharma wants us all to pop a pill (or two or three) whenever we feel pain. We’re constantly being programmed to believe—via highly effective advertising as well as in-person consultations with doctors—that prescription medications and over-the-counter drugs will alleviate our pain.

Except that this promise of pain relief may be a lie.

According to a 2022 study that’s been downloaded nearly 94,000 times, some anti-inflammatory drugs used to treat chronic pain may actually exacerbate the pain in the long run.^[2]

In fact, the use of anti-inflammatory medication was associated with an increased risk of persistent pain.

So those pain relievers you’ve been prescribed to help you?

They may be worsening your pain.

How acute pain becomes chronic

To better understand how acute pain becomes chronic, an international team of twenty scientists conducted a series of experiments intended to illuminate the body’s physiological mechanisms responsible for the progression from acute to chronic pain.

This research team, as they explain in their study, “Acute inflammatory response via neutrophil activation protects against the development of chronic pain,” analyzed the genes of nearly one hundred people (n=98) afflicted with acute low back pain at an initial point in time and then again three months later.

Skim this summary if you’re not a science geek. Grab yourself a cuppa tea or coffee if your heart pounds with joy at the nitty gritty details.

At the initial evaluation, the research subjects rated their pain on an average of 6.8 on a scale from 0 to 10, with the minimum being 4 and the maximum 10.

The first thing the researchers noticed at follow-up was that the average had dropped to 3.2, but the range of pain had expanded to 0 to 10.

The scientists then divided the subjects into two groups of 49 based on their follow-up pain ratings.

The group that had lower average pain at follow-up was labeled “R” for “Resolved” pain.

The group reporting higher pain at follow-up was labeled “P” for “Persistent” pain.

Then the researchers compared the genetic expression between the two groups during two visits.

Changes in gene expression

At the first visit, there were no differences of genome-wide statistical difference between the resolved pain and the persistent pain groups.

But at the second visit—and here’s where it gets interesting to those of us who like combing through the weeds—there were over 1,700 genes differentially expressed at “the genome-wide scale.”

The researchers found that, for the “Resolved” group, inflammatory genes were up-regulated, which means they were more active, at the start of the study and downregulated (less active) at the end.

But for the “Persistent” pain group, they didn’t note changes in inflammatory gene expression.

In simpler terms, something was happening in the bodies of the people whose pain was gone that just wasn’t happening in the people with persistent pain.

The changes in gene expression related to inflammatory pathways. So, the scientists then examined several types of immune cells.

They found significant differences between the two groups in certain cells:

1. neutrophils
2. CD8+ T cells
3. natural killer cells
4. mast cells

The effect was particularly pronounced for neutrophils. Neutrophils are a type of white blood cell that is called to areas of tissue damage.

While neutrophils decreased for both groups, the patients with resolved pain had much higher levels of neutrophils initially and a much sharper drop in neutrophils over time.

Replicating their results

Then, to find out if their results were true for other kinds of chronic pain, the scientists decided to try to replicate their analysis with a group of people suffering from a jaw pain called temporomandibular disorder or TMD.

Just like with those suffering from back pain, the jaw pain resolved at the three-month mark for some of the patients. Similarly, about 80 percent of genes associated with neutrophils were more expressed in the resolved groups with both lower back pain and TMD patients.

If you’re still with me, what does it all mean? This research strongly suggests that the body’s initial inflammatory response is a crucial part of resolving acute pain.

Steroid injections increase pain

Their next experiment was to see what happened when the initial inflammatory response was tinkered with. To test this, the research team injured mice to intentionally cause them pain (I know. If you’re anything like me, this part of their work is also making you cringe).

Then they injected one group of mice with dexamethasone, a powerful immune-suppressing steroid, for six days and the other group of mice with a placebo.

The mice injected with steroids fared poorly: their pain increased over time.

So was this due to the anti-inflammatory nature of the dexamethasone steroid treatment or because of some other component of the pain-relief action?

To find out, the scientists also tested the NSAID diclofenac, and three pain-relievers with no known anti-inflammatory action: gabapentin, morphine, and lidocaine.

As you might expect by now, only the anti-inflammatory, diclofenac, significantly prolonged the rodents’ pain.

So maybe inflammation can be beneficial?

In these experiments, early treatment with both steroid and nonsteroidal anti-inflammatory drugs offered short-term pain relief but, ironically, led to prolonged pain in the longer term.

And when the rodents’ neutrophils were intentionally damaged (via injections of an antibody), the mice also experienced longer-term pain.

“Inflammation is painful, but this inflammation is needed for our body to resolve pain,” Dr. Luda Diatchenko, M.D./Ph.D., professor in the Faculty of Medicine in the Department of Anesthesia at McGill who was the corresponding author on the study, said in an interview.

“Pain resolution is an active process that requires neutrophil activation.”

The take-away: Decreasing acute inflammation, either with steroids or NSAIDs, may have an unintended potentially long-lasting side effect: more pain.

So what do you do if you’re in pain?! (Besides cursing out my uncle Danny?)