Drug May Help in Managing Morphine Tolerance

Etanercept Restores Morphine Responsiveness in Rats

Newswise — A drug called etanercept can restore responsiveness to the pain-relieving effects of morphine in rats that have developed morphine tolerance, reports a study in the February issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

The experimental results suggest that etanercept—which blocks the inflammatory cytokine tumor necrosis factor (TNF)-alpha—could provide a useful new approach to "extend the effectiveness" of morphine and related drugs (opioids) for pain control. The lead study author of the new study is Dr. Chih-Shung Wong of Cathay General Hospital, Taipei, Taiwan. Etanercept Restores Morphine Responses, Blocks Spinal Inflammation

Morphine and other opioid drugs play an important role in the treatment of severe pain. However, the development of tolerance—requiring much higher doses for effective pain control—is an important limiting factor on their use.

The authors designed an experiment to evaluate the effects of etanercept in rats that had been made morphine tolerant. When these animals were treated with etanercept, it restored up to 60 percent of their responsiveness to morphine.

Morphine tolerance was associated with changes in the levels of certain inflammation-promoting proteins, called cytokines. When the animals were treated with etanercept, expression of the inflammatory cytokines was significantly reduced, in particular Tumor necrosis factor-alpha, often called TNF-. These changes were accompanied by reduced levels of activation of specialized spinal cord immune cells, called microglia.

Through its ability to block TNF- etanercept is an effective treatment for rheumatoid arthritis and other inflammatory autoimmune diseases. TNF- is expressed in spinal cord cells, and plays a significant role in the development of several neurological disorders.

The new results show that etanercept can restore much of the pain-relieving effect of morphine in morphine-tolerant rats. Etanercept treatment also reduces expression of inflammation-promoting cytokines, as well as activation of the microglia.

"This suggests that TNF-alpha is an important proinflammatory cytokine that mediates the neuroinflammation associated with morphine tolerance," Dr Shen and colleagues write. The study provides researchers with important new clues regarding the molecular pathways leading to morphine tolerance.

Although much further research is needed, the results also raise the possibility that etanercept could provide a useful new treatment for restoring the pain-relieving effects of morphine in patients who have become morphine-tolerant. This could be an important new tool for the management of patients with severe chronic pain, who are often left with few options for effective pain control once morphine tolerance has developed. Given the new findings on the roles of TNF-alpha and inflammatory cytokines, Dr. Shen and co-authors conclude, "Evaluation of other potent anti-inflammatory drugs for morphine tolerance management is…warranted to further explicate the features of morphine tolerance."

Read the full study in Anesthesia & Analgesia

About the IARSThe International Anesthesia Research Society is a nonpolitical, not-for-profit medical society founded in 1922 to advance and support scientific research and education related to anesthesia, and to improve patient care through basic research. The IARS contributes nearly $1 million annually to fund anesthesia research; sponsors an annual forum for anesthesiology leaders to share information and ideas; maintains a worldwide membership of more 15,000 physicians, physician residents, and others with doctoral degrees, as well as health professionals in anesthesia-related practice; sponsors the SAFEKIDS initiative; and publishes the journal Anesthesia & Analgesia. Additional information about the society and the journal may be found at www.iars.org and www.anesthesia-analgesia.org.

About Anesthesia & AnalgesiaAnesthesia & Analgesia was founded in 1922 and was issued bi-monthly until 1980, when it became a monthly publication. A&A is the leading journal for anesthesia clinicians and researchers and includes more than 500 articles annually in all areas related to anesthesia and analgesia, such as cardiovascular anesthesiology, patient safety, anesthetic pharmacology, and pain management. The journal is published on behalf of the IARS by Lippincott Williams & Wilkins (LWW), a division of Wolters Kluwer Health.