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

About a third of the world’s adult population, including 25 million Britons, will suffer from chronic pain in their lifetime. Chronic pain is defined as acute pain caused by injury or surgery that persists beyond the healing period – a hallmark of many medical conditions.

Often, the intensity of chronic pain does not necessarily correlate with 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 don’t fully understand why some people develop chronic pain and others don’t, or how acute pain becomes chronic over time, but there is thought to be a genetic contribution to chronic pain. This lack of understanding makes chronic pain extremely difficult to treat.

Costs to the UK economy from chronic back pain alone are estimated at £10 billion 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 sharp rise in opioid prescriptions 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 searched for DNA risk markers associated with ‘chronic multi-site pain’ within the UK Biobank, a group of over half a million people who provide health data for research and study. Multisite chronic pain characterizes the number of places people report chronic pain in their body, on a scale of zero to seven.

It was the largest genetic study of chronic pain ever conducted, involving more than 380,000 participants, 10 times more than the most recent comparable study conducted by 23andMe in collaboration with pharmaceutical company Pfizer. Many previous genetic studies have 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 difficult to treat?

We wanted to identify genetic risk factors for chronic pain in general and vulnerability to chronic pain, rather than for specific pain syndromes or conditions. A growing body of research indicates that chronic pain can exist on a continuous ‘spectrum’, with the original disease, condition or injury providing less insight into the 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 distributed across the genome and suggested that genes expressed in the adult brain, which are involved in neuroplasticity or brain remodeling, 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, in particular major depressive disorder (MDD). It is a common psychiatric disorder and one of the largest contributors to ‘years lived with disability’ – a measure of disease burden – worldwide.

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

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 approximately 50% of 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, among others.

We used our genetic knowledge to examine whether chronic pain could have a causative 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 randomization, which calculates causal effects from datasets where all the data was collected at the same time.

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

Our findings reveal new insights into the genetics and possible mechanisms of chronic pain and may open new avenues for better treatments. This study may also help identify people at higher genetic risk for developing chronic pain. It is clear that chronic pain overlaps with a range of other disorders and diseases, but our discovery that it causes MDD could be of clinical and public health significance worldwide.

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