New genetic study links chronic pain to depression, BMI, schizophrenia, arthritis and PTSD

Keira Johnston, University of Glasgow

Around one third of the world’s adult population, including 25m Britons, will experience chronic pain during their lifetime. Chronic pain is defined as acute pain from injury or surgery that persists beyond the healing period – a feature of many medical conditions.

Often the intensity of chronic pain does not necessarily match the degree of tissue damage, as can be seen with arthritis. It can even be caused by very mild trauma, such as a needle stick injury.

We do not fully understand why some people develop chronic pain and others don’t, or how acute pain becomes chronic over time, but it is thought that there is a genetic contribution to chronic pain. This lack of understanding makes chronic pain extremely difficult to treat.

Costs to the UK economy due to chronic back pain alone are estimated at £10 bn and in the US, the current epidemic of opioid-related deaths has been described as a national crisis by the National Institutes of Health. The UK has also seen a stark rise in opioid prescribing and opioid-related deaths in recent years.

Digging into DNA

To better understand the biology behind chronic pain we performed a Genome Wide Association Study (GWAS). We looked for DNA risk markers associated with “multisite chronic pain” within the UK Biobank, a group of over half a million individuals who provide health data for research and study. Multisite chronic pain characterises the number of places people report chronic pain in their body, on a scale from zero to seven.

This was the largest genetic study of chronic pain ever conducted, involving more than 380,000 participants – 10 times larger than the most recent comparable study carried out by 23andMe in collaboration with pharmaceutical company Pfizer. Many previous genetic studies focused on specific chronic pain conditions, such as migraine, but we looked at chronic pain regardless of the underlying injury or condition.

Read more: What is chronic pain and why is it hard to treat?

We were interested in identifying genetic risk factors for chronic pain in general and vulnerability to chronic pain, rather than for specific pain syndromes or conditions. There is a growing body of research indicating that chronic pain may exist on a continuous “spectrum” , with the original disease, condition or injury providing less insight into underlying mechanisms compared to a study of the chronic pain itself.

Important discoveries

We found 76 independent DNA risk markers, or Single Nucleotide Polymorphisms (SNPs), associated with chronic pain. These were spread across the genome and suggested that genes expressed in the adult brain, which are involved in neuroplasticity or brain remodelling, are involved in the development of chronic pain.

Our findings also suggested that genes involved in the cell cycle were associated with chronic pain – this could indicate a role for the immune system or for cell generation that occurs as part of neuroplasticity.

We also looked at how DNA risk markers were shared between chronic pain and other disorders, particularly major depressive disorder (MDD). This is a common psychiatric disorder and one of the largest contributors to “years lived with disability” – a measure of disease burden – globally.

Chronic back pain costs the UK economy £10 bn a year. Shutterstock

People with MDD will often also experience chronic pain and vice versa, at very high rates. We found that chronic pain and MDD overlap genetically, with around 50% of the DNA risk markers for chronic pain also found to be risk markers for MDD. We also found genetic overlap between chronic pain and schizophrenia, body-mass index, rheumatoid arthritis and post-traumatic stress disorder, amongst others.

We used our genetic insights to examine whether chronic pain could have a causal effect on MDD, and vice versa, and found that chronic pain was indeed a cause of MDD, but the reverse did not apply. This was done via a type of analysis called Mendelian randomisation, which allows calculation of causal effects from datasets where all the data was collected at the same time.

The findings of our study can also potentially be used to predict which people are most at risk for developing chronic pain, using “polygenic risk scoring based on an individual’s DNA risk markers.

Our findings reveal new information on the genetics and possible mechanisms of chronic pain and may provide new avenues for better treatments. This study may also help to identify individuals at higher genetic risk of developing chronic pain. It is clear that chronic pain overlaps with a range of other disorders and diseases, but our finding that it causes MDD could be important clinically and for public health around the world.

Keira Johnston, Researcher Institute of Health and Well-being, University of Glasgow

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Featured Image: Kinga Cichewicz on Unsplash

Similar Posts