Irvine: Brain inflammation caused by chronic nerve pain alters activity in regions that regulate mood and motivation, suggesting for the first time that a direct biophysical link exists between long-term pain and the depression, anxiety and substance abuse seen in more than half of these patients, UC Irvine and UCLA researchers report. This breakthrough finding also points to new approaches for treating chronic pain, which is second only to bipolar disorder among illness-related causes of suicide. About a quarter of Americans suffer from chronic pain, making it the most common form of enduring illness for those under the age of 60. The Institute of Medicine estimates that this costs our society more than $635 billion per year.
In work with rodents, Catherine Cahill, associate professor of anesthesiology & perioperative care at UCI; Christopher Evans of UCLA’s Brain Research Institute;
and colleagues discovered that pain-derived brain inflammation causes
the accelerated growth and activation of immune cells called microglia.
These cells trigger chemical signals within neurons that restrict the
release of dopamine, a neurotransmitter that helps control the brain’s
reward and pleasure centers.
The study also reveals why opioid drugs such as morphine can be
ineffective against chronic pain. Morphine and its derivatives normally
stimulate the release of dopamine. But in research on mice and rats in
chronic pain, Cahill and her colleagues learned that these drugs failed
to stimulate a dopamine response, resulting in impaired reward-motivated
Treating these animals in chronic pain with a drug that inhibits
microglial activation restored dopamine release and reward-motivated
behavior, Cahill said.
“For over 20 years, scientists have been trying to unlock the
mechanisms at work that connect opioid use, pain relief, depression and
addiction,” she added. “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 results of the five-year study appear online in The Journal of Neuroscience.
Next, Cahill and her team aim 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.”