A discovery by researchers at the Indiana University School of Medicine can make morphine a safer and more effective drug.
An orphan drug originally used for HIV treatment has been found to short-circuit the process that results in additional sensitivity and pain from opioid use.
The researchers said the finding in animal models might ultimately make morphine a safer and more effective drug.
Today, they are used widely for chronically painful conditions like osteoarthritis and back pain and may need to be prescribed for decades.
Morphine, the gold standard for controlling moderate to severe pain, has debilitating side effects including reduced respiration, constipation, itching and addiction.
Patients also develop a tolerance to morphine, which can lead to a complicated spiral.
"In addition to the recognized side effects, morphine actually creates sensitivity and causes more pain through inducing an inflammatory response in the body," said first author Natalie Wilson.
This increased sensitivity is clinically known as opioid-induced hyperalgesia (OIH).
Frequently, patients receiving opioids for pain control may actually become more sensitive to certain painful stimuli necessitating an increased opioid dosage.
OIH may also represent one of many reasons for declining levels of analgesia while receiving opioids or a worsening pain syndrome.
Co-author Fletcher A. White said that morphine sets into motion a cascade of events, one of which is to increase molecular communication to and from the nerves by a protein known as CXCR4.
This increase in CXCR4 signalling contributes to a neuroinflammatory response causing increased sensitivity and additional pain.
The researchers administered AMD3100, an orphan drug known to block the CXCR4 response, to rats.
By halting the signalling process, the researchers interrupted the OIH response.
"If this translates appropriately in people, this application would likely make morphine a safer, more effective drug for chronic pain control," said White.
The study is reported in the March 25 issue of Brain, Behavior and Immunity.