How Chronic Pain Changes Mood and Motivation

By Pat Anson, Editor

Researchers in California have found the first biological evidence that chronic pain alters regions in the brain that regulate mood and motivation -- raising the risk of depression, anxiety and substance abuse.

In animal studies at UCLA and UC Irvine, researchers found that brain inflammation in rodents that was caused by chronic nerve pain led to accelerated growth and activation of immune cells called microglia. Those cells trigger chemical signals within the brain that restrict the release of dopamine, a neurotransmitter that helps control the brain's reward and pleasure centers.

"For over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction," said Catherine Cahill, associate professor of anesthesiology & perioperative care at UCI, Christopher Evans of UCLA's Brain Research Institute. "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 study also revealed why opioid drugs such as morphine and cocaine may lose their effectiveness as animals transition from acute pain to chronic pain. Cahill and her colleagues learned that opioids fail to stimulate a dopamine response in mice and rats, resulting in impaired reward-motivated behavior.

Treating the rodents with a long-acting antibiotic called minocycline inhibited microglial activation, and restored dopamine release and reward-motivated behavior. That finding suggests that a similar approach could be used in treating chronic pain in humans.

"Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic signaling and reward behavior. These results have broad implications that are not restricted to the problem of pain, but are also relevant to affective disorders associated with disruption of reward circuitry," the study found.

The results of the five-year study appear online in the Journal of Neuroscience.

Cahill and her research team are now trying to establish that pain-derived changes in human brain circuitry can account for mood disorders.

"We have a drug compound that has the potential to normalize reward-like behavior," she said, "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."