Chronic pain can outlast inflammation, the usual driver of pain in the body – a study in mice suggests a vitamin supplement could help relieve it

By Grace Wade

The mitochondria in certain sensory neurons could be linked to chronic pain

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A type of vitamin B3, called nicotinamide riboside, alleviates persistent pain in mice, suggesting that it may potentially treat chronic pain in humans as well.

Inflammation – the body’s first line of defence against injury and pathogens – is a main driver of pain. Yet, some people continue to experience pain even after inflammation has resolved.

To understand why, Niels Eijkelkamp at Utrecht University in the Netherlands and his colleagues analysed inflammation’s impact on mitochondria, the powerhouses of cells. Previous research has linked chronic pain to dysfunctional mitochondria, particularly those in specialised nerve cells, called sensory neurons, which detect changes in the environment.

The researchers injected a substance that triggers inflammation into the hind paws of 15 mice. They then measured the amount of oxygen consumed by mitochondria in the sensory neurons of the animals, which indicates mitochondrial function. They found that a week later, after inflammation had resolved, mitochondria consumed significantly more oxygen than they had before the injection, suggesting inflammation caused lasting changes to their function. Further experiments linked these mitochondrial changes to greater pain sensitivity in the rodents even after their inflammation resolved.

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The researchers then analysed the molecular byproducts of chemical reactions, called metabolites, inside the mitochondria of the animals. They compared these to the mitochondrial metabolites in mice that had not experienced induced inflammation. The team found that after inflammation had resolved, mice had lower than expected levels of nicotinamide riboside in the mitochondria of their sensory neurons. This is a type of vitamin B3 critical for mitochondrial function.

So, about a week after inducing inflammation in a separate group of 12 mice, Eijkelkamp and his team gave half of them a high dose of nicotinamide riboside – 500 milligrams per kilogram of body weight. By comparison, the recommended daily amount of vitamin B3 for most adults is between 14 and 16 milligrams. They then assessed the animals’ sensitivity to pain by measuring how quickly they pulled their paw away from heat. Mice that hadn’t received nicotinamide riboside retracted their paw twice as fast, on average, as those that did, suggesting the supplement alleviates pain.

Together these findings indicate two things: first, that inflammation can impair mitochondrial function in sensory neurons and that these impairments increase the risk of chronic pain, even after inflammation has resolved. Second, that taking nicotinamide riboside supplements may help treat this chronic pain by restoring mitochondrial function.

However, people with chronic pain shouldn’t rush to take these supplements. “[This research] is still in rodents. How does it translate to humans? We really have to see that first,” says Eijkelkamp. Clinical trials may show nicotinamide riboside has no effect or even unintended consequences, he says.

Even if these findings do translate to humans, they probably only apply to certain types of chronic pain, such as that of chronic inflammatory diseases, says Eijkelkamp. For instance, more than 20 per cent of people with rheumatoid arthritis – a chronic condition characterised by persistent joint inflammation – continue to have pain even with low levels of inflammation. As such, it would make sense to test these findings in that demographic first.

Journal reference:

Cell Reports Medicine DOI: 10.1016/j.xcrm.2023.101265