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Sickness behaviour and chronic pain

Paul Ingraham ARCHIVEDMicroblog posts are archived and rarely updated. In contrast, most long-form articles on are updated regularly over the years (see updates page).

We’ve all been there: feverish, or close to it. Deep, sickly fatigue. Everything hurts. You swear you can feel individual molecules banging into your skin, and like they might just break you, like a thin pane of glass. What causes that nasty feeling?

An inflamed nervous system!

Neuroinflammation is almost synonymous with that feeling of gross exhaustion and fragility. And that feeling has a job to do: it modifies behaviour. Specifically, it forces rest. “No foraging this week!” Many symptoms of illness are “friendly fire” from the immune system, which is tuned to protect us without much regard for our happiness. Neuroinflammation is a classic example.

An uncomfortable feature, but not a bug

That gross feeling of exhausted fragility causes sickness behaviour, which occurs in all animals as a normal response to threats to their overall health (see Lyon et al). It is a highly “conserved” trait, which is a biologist’s way of saying that it’s too important for any organism to evolve away from. Critters have probably been getting neuroinflamed for about as long as there have been critters.

In modern medicine, sickness behaviour has traditionally been defined as a response to major infections, but it’s clearly not limited to that: it also fires up after major injuries, for instance. After my wife’s terrible accident in 2010 — causing a major brain injury and spinal fracture, plus several other less serious fractures and lacerations — a doctor warned her not to underestimate how profound and prolonged her fatigue would be, and she really was exhausted for a good year. It’s not exactly that healing is metabolically “expensive” — it is, and that’s why we need rest after major injuries, but neuroinflammation is specifically how our bodies guarantee that resting happens.

Recent research is revealing that neuroinflammation is kind of a big deal, an elaborate generalized response to almost any kind of significant adversity.

A response that can get out of hand, much like pain.

When neuroinflammation goes wrong

In humans, neuroinflammation might even be triggered just by perceived threats to health, something we are much better at imagining than cats or capybaras (or zebras, which is why Why Zebras Don’t Get Ulcers). And it is probably a factor in many cases of medically unexplained symptoms and chronic pain (like fibromyalgia, see Albrecht et al).

And it gets worse! Once established, in the right conditions, neuroinflammation may be somewhat self-sustaining, a perpetual malaise machine, obnoxiously persisting even without an ongoing threat (perceived or otherwise). In that scenario, you would continue to feel sick even well after the original problem resolved.

Neuroinflammation is probably also a major driver of sensitization, the specific way that it produces that “fragile” feeling. Lowering the pain threshold has an obvious role to play in sickness behaviour, a fine example of how the body says no. This link has not been firmly established yet, but science is closing in, and we already know for sure that chronic widespread pain is closely linked to sensitization. So sensitization bridges the gap between the problem of chronic widespread pain and the mechanism of neuroinflammation, and so “neuroinflammation drives widespread chronic pain via central sensitization” (see Ji et al).

Tip of the iceberg

This has been a short, high-level primer on neuroinflammation. Look at that last link for a dose of the mind-boggling complexity of the details. Physiology makes 3-dimensional chess look easy.

I think the topic of neuroinflammation is going to come up on frequently over the next few years. I suspect it has the potential to explain a lot about chronic widespread pain and other medically unexplained symptoms. I’ve already updated a couple articles with this topic — Chronic, Subtle, Systemic Inflammation and 34 Surprising Causes of Pain — but more are definitely coming. Meanwhile, if you’d like to read more about it, I recommend this fairly readable exploration of the relationship between fibromyalgia and neuroinflammation.

And a major “see also”: Todd Hargrove’s description of “A Systems Perspective on Chronic Pain.”

To be continued with a part-2-ish discussion of the evolutionary necessity of neuroinflammation and, therefore, also of chronic pain: What if chronic pain is a feature, not a bug? Evolution is more interested in survival than comfort. Acute pain is definitely a necessary evil from that perspective, and chronic pain may be too.

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