A research team including a UAB scientist has discovered how chronic pain causes depression and are looking into whether the drug ketamine may be helpful in alleviating it.

Dr. Lingyong Li of UAB worked with a team of scientists at other universities to test the brains of mice to better understand the mechanism behind depression stemming from chronic pain, publishing the findings of their study in The Journal of Clinical Investigation.

“Our study provides guidance and a foundation for the clinical treatment of chronic pain-induced mood disorders. Our study also provides a reference for studying stress-induced depression,” said Li.

The team studied the brains of mice to identify how chronic pain leads to depression through an increase in hypersensitivity in part of the brain.

“Chronic pain is often comorbid with mood disorders, like depression and anxiety, which intensify patients suffering and are clinically difficult to treat,” said Dr. Li.

That hypersensitivity was caused by a rise in connections between neurons in the anterior cingulate cortex, the team discovered. One protein, called Tiam1, was key to the process, the team found. The exact reason was previously little understood, said Li.

“Targeting Tiam1 to normalize the number and strength of neuron-neuron connection can relieve depressive symptoms in chronic pain patients,” said Li.

The next stage in research will be testing the use of ketamine, a drug typically used as an anesthetic, as an antidepressant.

In 2019 the FDA approved a nasal spray called Esketamine, which is derived from ketamine, to treat depression. It is the first new medication for major depression approved in decades, according to Yale Medicine.

Low doses of ketamine have successfully been used as anti-depressants in animals by blocking hypersensitivity from chronic pain, according to Li.

UAB’s research may help develop treatments for depression from chronic pain from ketamine, which is used as an anesthetic. Li plans to develop a clinical trial with doctors to test ketamine’s effectiveness in people experiencing depression from chronic pain.

Dr. Li has worked on other studies to develop drug treatments for chronic pain from nerve injury, diabetes, inflammation and chemotherapy. Opioids are the most common treatment for chronic pain, but they often cause side effects and can lead to addiction.