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Is stress inflammatory?

 •  • by Paul Ingraham
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Weekly nuggets of pain science news and insight, usually 100-300 words, with the occasional longer post. The blog is the “director’s commentary” on the core content of a library of major articles and books about common painful problems and popular treatments. See the blog archives or updates for the whole site.

Another “inflammatory” post today. The last one was about tendinopathy.

There are strong but murky links between chronic pain and stress (and all its cousins: anxiety, insomnia, depression, social isolation, etc.) We still don’t know if stress directly causes chronic pain and other health problems — though there are signs that it can (Thompson) — or if it “just” feeds back into it (Elbinoune). It’s possible that low-grade chronic inflammation is one way that stress can become painful. It might even be the way.

Inflammation is immunity’s fingerprint, and we know (or strongly suspect) that “immunity is tuned by one’s emotions, personality, and social status as well as by other life style variables like sleep, nutrition, obesity, or exercise” (Lasselin). We know that nervous-wreck monkeys are inflamed, their immune systems a mess. Dr. Robert Sapolsky, regarding a study of low-status monkeys (Snyder-Mackler), who have really hard lives:

At the end of the day, being a chronically subordinate nonhuman primate and being a human mired at the bottom of the socioeconomic scale are similar in the most fundamental ways. You have remarkably little control and predictability in your life, your outlets for frustration are limited, and it’s relatively hard to access social support. That’s the prescription for chronic, stress-related maladies.

The same thing probably happens in humans. We suspect that rough childhoods may be a risk factor for several disorders that probably share inflammation as a mechanism (Burke).

Aren’t stress hormones anti-inflammatory?

This is all a bit counterintuitive, because we “know” that stress can actually suppress immunity, and that stress hormones — corticosteroids — are impressively anti-inflammatory. But that’s short term stress. It’s insanely complicated, but prolonged stress almost certainly does the opposite: overstimulates the immune system, causing chronic excessive inflammation and likely autoimmune disease risk too.

In the very short term (minutes), stress is indeed an immune stimulator (inflammatory). But then, almost right away, that effect gets reeled in to prevent collateral damage: you don’t want sustained immune stimulation! This suppressive effect is robust, and it’s why stress/steroids suppress inflammation.

In chronic stress, the stimulatory phase keeps happening over and over again, and the suppressive phase never quite catches up, and so overall immune system activation gradually ratchets up … and up … and up. Ergo, long term stress is inflammatory.

Chart showing a sawtooth pattern of immune function increasing and decreasing with repeated stressors, but never quite recovering before increasing again, producing a steady upward trend.

“A schematic representation of how repeated stress increases the risk of autoimmune disease,” adapted from Sapolsky’s Why Zebras Don’t Get Ulcers.

Sapolsky goes deep on this topic in Why Zebras Don’t Get Ulcers, and I am completely relying on him for this point. I hope I’ve boiled it down to the essentials correctly. His bottom line:

The system apparently did not evolve for dealing with numerous repetitions of coordinating the various on-and-off switches, and ultimately something uncoordinated occurs, increasing the risk that the system becomes autoimmune [inflammatory].

This is an excerpt from an update to my main article about systemic inflammation and pain:

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