Chronic pain and depression are linked by brain gene changes

People who have chronic pain are more likely to experience mood disorders, but it’s not clear how this happens. Now a study in mice has found that chronic pain can induce genetic changes in brain regions that are linked to depression and anxiety, a finding that may lead to new treatments for pain.

“At least 40 per cent of patients who suffer from severe forms of chronic pain also develop depression at some point, along with other cognitive problems,” says Venetia Zachariou of the Icahn School of Medicine at Mount Sinai in New York.

To see if there might be a genetic link between these conditions, Zachariou and her team studied mice with damage to their peripheral nervous system. These mice show symptoms similar to chronic pain in people – they become hypersensitive to harmless touch, and avoid other situations that might also cause them pain.

Until now, pain behaviour in mice had only been studied for at most a week at a time, says Zachariou, whose team monitored their mice for 10 weeks. “At the beginning, we saw only sensory deficits and pain-like symptoms. But several weeks later, the animals developed anxiety and depression-like behaviours.”

The team then examined gene activity in three regions in the mouse brains we know are associated with depression and anxiety. Analysing the nucleus accumbens, medial prefrontal cortex, and periaqueductal gray, they found nearly 40 genes where activity was significantly higher or lower than in mice without the nervous system damage.

Inflammation link

Many of these genes had already been linked to depression and anxiety in people as well as in mice under chronic stress. Some of these genes are involved in inflammation, which may provide a clue to the link between chronic pain and depression. Inflammation in the brain is known to be associated with depression in people.

Neuroimaging studies have shown that these three brain areas are involved in pain and emotional processing, and changes are seen in these networks when people experience chronic pain, says David Seminowicz of the University of Maryland School of Dentistry in Baltimore, Maryland. “Understanding the genetic and epigenetic factors underlying these changes will help us identify treatment targets. The study provides the groundwork for future research to test these mechanisms more directly,” says Seminowicz.

This may lead to better drugs. Currently, some chronic pain patients are given anti-depressants to treat their pain. “But anti-depressants have a slow onset of action. It takes weeks to months to start alleviating pain, or mood,” says Zachariou. “There is definitely room for better drugs.”

Vania Apkarian, a pain expert at Northwestern University, Chicago, Illinois, says the study is an important step forward, but cautions against conflating chronic pain with depression and anxiety in all situations. “There are also a large number of genes expressed separately for the distinct conditions. One has to be careful to determine which are more critical,” he says.


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