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Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain

PainSci » bibliography » Willemen et al 2023
Tags: inflammation, sensitization, chronic pain, pain problems, neurology

PainSci commentary on Willemen 2023: ?This page is one of thousands in the bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.

Why does pain often last long after healing should be done? We may finally know! Willemen et al. supplied this possible answer:

“mitochondrial and metabolic disturbances in sensory neurons”

Basically. Clear as mud? Let’s translate and elaborate…

Sometimes, after an injury or illness, pain is amazingly persistent even long after the initial problem seems to be healed. The study showed that a temporary bout of inflammation can permanently “damage” sensory neurons, change them in a bad way, making them making them more sensitive for the long haul, specifically due to a change in their “batteries” (mitochondria). Tweaking these mitochondrial changes — either by slowing down their activity, messing with a specific protein’s expression, or adding in a missing metabolite — can prevent that long-lasting sensitization. Which also proved that mitochondrial dysfunction was the problem in the first place. Very cool.

Alas, they did this in rats, not people. Still, this is some great basic pain science. I have spent most of my career wondering why twenty-year-old ankle sprains can still throb and twinge, and this may well be the explanation. Good to know!

~ Paul Ingraham

original abstract Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

Pain often persists in patients with an inflammatory disease, even when inflammation has subsided. The molecular mechanisms leading to this failure in pain resolution and the transition to chronic pain are poorly understood. Mitochondrial dysfunction in sensory neurons links to chronic pain, but its role in resolution of inflammatory pain is unclear. Transient inflammation causes neuronal plasticity, called hyperalgesic priming, which impairs resolution of pain induced by a subsequent inflammatory stimulus. We identify that hyperalgesic priming in mice increases the expression of a mitochondrial protein (ATPSc-KMT) and causes mitochondrial and metabolic disturbances in sensory neurons. Inhibition of mitochondrial respiration, knockdown of ATPSCKMT expression, or supplementation of the affected metabolite is sufficient to restore resolution of inflammatory pain and prevents chronic pain development. Thus, inflammation-induced mitochondrial-dependent disturbances in sensory neurons predispose to a failure in resolution of inflammatory pain and development of chronic pain.

This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:

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