The Brain May Increase Opioid Receptors to Cope With Chronic Pain

Participants' pain thresholds positively correlated with their opioid receptor availability.

There is evidence that in people with arthritis, the brain may increase its amount of opiate receptors to better cope with chronic pain, according to research published in the journal Pain.

It has long been known that prolonged processing of pain results in the release of endogenous opioid peptides and subsequent activation of opioid receptors (OpR) in the central nervous system.

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According to Christopher Brown, PhD, senior research associate with the School of Clinical Medicine at the University of Cambridge in the United Kingdom, and colleagues, there is evidence from animal studies that opioid receptors can increase to cope with pain, but that “evidence for such a mechanism in humans is lacking.”

To search for evidence of a similar relationship between chronic pain and OpR availability in humans, the researchers scanned 17 participants with arthritis pain and 9 healthy controls with positron emission tomography and the radiotracer 11C-diprenorphine to calculate parametric maps of their OpR availability.

When Dr. Brown and his team applied heat to the participants with a laser stimulator, the researchers found that pain thresholds positively correlated with opioid receptor availability, suggesting that the more opioid pain receptors there are in the brain, the higher the ability to withstand pain.

Although this doesn’t directly test the researchers’ hypothesis, the results are consistent with their hypothesis that OpR sites may increase in people with chronic pain. Increased OpR sites would allow the body to enhance natural opiates in the brain, such as endorphins.

“This is very exciting because it changes the way we think about chronic pain,” said Professor Anthony Jones, director of the Manchester Pain Consortium, in a press release. “There is generally a rather negative and fatalistic view of chronic pain. This study shows that although [those who experience chronic pain] are more physiologically vulnerable, the whole pain system is very flexible and that individuals can adaptively upregulate their resilience to pain.”

“Although the mechanisms of these adaptive changes are unknown, if we can understand how we can enhance them, we may find ways of naturally increasing resilience to pain without the side effects associated with many pain killing drugs,” said Dr. Brown.


Brown CA, Matthews J, Fairclough M, et al. Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain? Pain. 2015; doi:10.1097/j.pain.0000000000000299.