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Safer & more effective morphine may be possible with Indiana University discovery

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www.ProHealth.com • March 28, 2011


In addition to the recognized side effects, opioid pain drugs can actually create sensitivity and cause more pain by inducing an inflammatory response in the body.

Researchers at Indiana University report that an orphan drug originally used for HIV treatment can short-circuit the process that results in additional sensitivity and pain from opioid use - promising to make morphine a safer and more effective drug.

The research, confined to animal testing so far, was reported Mar 25 in Brain, Behavior and Immunity (“CXCR4 Signaling mediates morphine-induced tactile hyperalgesia.”)

Opioids may create a complicated spiral.

Traditionally, opioids were used to relieve pain following surgery, from cancer, and at the end of life. Today they are used widely for chronically painful conditions like osteoarthritis and back pain, and may need to be prescribed for decades.

But 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," says first author Natalie Wilson, a National Science Foundation Fellow at the IU School of Medicine.

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 pain relief while receiving opioids, or a worsening pain syndrome.

"The drug itself is producing its own new pain. I tend to view it as an injury, as it appears to be creating another pain," says IU anesthesia research director Fletcher A. White, PhD.

Specifically, Dr. White explains:

• 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 signaling contributes to a neuroinflammatory response causing increased sensitivity and additional pain.

Drs. Wilson and White and colleagues administered AMD3100, an orphan drug known to block the CXCR4 response, to rats.

By halting the signaling process, the researchers interrupted the opioid-induced hyperalgesia (OIH) response, Dr. White explains: "If this translates appropriately in people, this application would likely make morphine a safer, more effective drug for chronic pain control."

The research was funded by the National Institute on Drug Abuse. Co-authors are Richard J. Miller, PhD, and Hosung Jung, PhD, both molecular pharmacologists at Northwestern University.

____

Source: Indiana University School of Medicine news release, Mar 24, 2011




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