Brain inflammation links chronic pain with depression

The findings of the study, published in the Journal of Neuroscience, could lead to new methods of treatment for chronic pain, the most common form of enduring illness for people aged below 60 in the US.

Researchers from the University of California-Irvine(UCI) and the University of California-Los Angeles (UCLA) made their discovery after examining the growth of immune cells in the brains of mice and rats with chronic pain.

According to the American Academy of Pain Medicine (AAPM), pain affects more people in the US than diabetes, heart diseaseand cancer combined, with an estimated 100 million Americans experiencing chronic pain.

Chronic pain is also strongly associated with the development of other conditions such as depression, anxiety and substance abuse, with these three seen in more than half of patients with chronic pain. Among illness-related causes of suicide in the US, chronic pain is second only to bipolar disorder.

Catherine Cahill, associate professor of anesthesiology and perioperative care at UCI, and colleagues discovered thatinflammation in the brain caused by chronic pain increased the rate at which specific immune cells grew and became activated.

These cells, known as microglia, set off chemical signals in the brain that inhibited the release of dopamine, crucial to the regulation of areas of the brain associated with reward and pleasure.

Dopamine is one of the most important neurotransmitters, associated not only with the reward system of the brain but with cognitive and motor functions. Some studies have also linked disruption to the dopamine response with psychosis andschizophrenia.

Findings represent a 'paradigm shift' in pain research

Opioid drugs such as morphine are frequently used to relieve pain, but in patients with chronic pain they can be ineffective. The new study has now revealed why this might be the case.

These drugs typically stimulate a dopamine response, but the researchers found that no such response occurred in mice and rats with chronic pain. Reward-motivated behavior in the rodents was also impaired.

After using a drug that inhibits the activation of microglia, however, the researchers observed that dopamine release was restored, as was reward-motivated behavior.

"For over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction," states Cahill. "Our findings represent a paradigm shift which has broad implications that are not restricted to the problem of pain and may translate to other disorders."

The researchers are now hoping to establish whether biophysical alterations in the brain are behind the development of mood disorders associated with disruption of reward circuitry and chronic pain.

"We have a drug compound that has the potential to normalize reward-like behavior," explains Cahill, "and subsequent clinical research could then employ imaging studies to identify how the same disruption in reward circuitry found in rodents occurs in chronic pain patients."