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Sickness behaviour and chronic pain

 •  • 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.

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! Which sounds like sensationalistic nonsense preceding a sales pitch, but bear with me (and there’s nothing for sale).

Neuroinflammation is what creates 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 of the most prominent 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, 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 as long as there have been critters (about 600 million years).

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 — 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 indeed she was utterly exhausted for a good year. Healing is metabolically expensive, and so we need rest after major injuries.

Neuroinflammation is specifically how our bodies guarantee that the resting happens.

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

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

When neuroinflammation goes wrong

Neuroinflammation be a factor in many cases of medically unexplained symptoms and chronic pain (like fibromyalgia, see Albrecht et al), because it it generally has more triggers and goes wrong more and worse than is generally appreciated.

In humans, it’s conceivable that it could even be caused just by perceived threats to health — by stress — something we are much better at imagining than cats or capybaras (or zebras, which is why Why Zebras Don’t Get Ulcers). This is highly speculative, however.

However it gets going, in the right (or wrong) 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 lousy even well after the original problem resolved.

Neuroinflammation is also a likely 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 clinical problem of chronic widespread pain and the biological 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 35 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.