An international team of researchers involving the University of Adelaide has made a major discovery that could lead to more effective treatment of severe pain using morphine.
Morphine is an extremely important drug for pain relief, but it can lead to a range of side-effects -- such as patients developing tolerance to morphine and increased sensitivity to pain. Until now, how this occurs has remained a mystery.
The team from the University of Colorado and University of Adelaide has shown for the first time how opioid drugs, such as morphine, create an inflammatory response in the brain -- by activating an immune receptor in the brain.
They have also demonstrated how this brain immune receptor can be blocked, laying the groundwork for the development of new therapeutic drugs that improve the effectiveness of morphine while reducing many of its problematic side effects.
The results of this research are published April 2 in the Proceedings of the National Academy of Sciences (PNAS).
"Because morphine is considered to be such an important drug in the management of moderate to severe pain in patients right around the world, we believe these results will have far-reaching benefits," says study co-author Dr Mark Hutchinson, ARC Research Fellow in the University of Adelaide's School of Medical Sciences.
Dr Hutchinson's team, including University of Adelaide colleague Professor Andrew Somogyi, conducted studies in mice to validate the work done at the University of Colorado by the teams of Assistant Professor Hubert Yin and Professor Linda Watkins.
"For some time it's been assumed that the inflammatory response from morphine was being caused via the classical opioid receptors," says Dr Hutchinson.
"However, we found instead that morphine binds to an immune receptor complex called toll-like receptor 4 (TLR4), and importantly this occurs in a very similar way to how this receptor detects bacteria.
"Our experiments in mice have shown that if this relationship with the immune receptor is disrupted, it will prevent the inflammatory response.
"This is an exciting result because it opens up possibilities for future drugs that promote the beneficial actions of morphine while negating some of the harmful side effects. This could lead to major advances in patient and palliative care," he says.
- Xiaohui Wang, Lisa C. Loram, Khara Ramos, Armando J. de Jesus, Jacob Thomas, Kui Cheng, Anireddy Reddy, Andrew A. Somogyi, Mark R. Hutchinson, Linda R. Watkins, and Hang Yin. Morphine activates neuroinflammation in a manner parallel to endotoxin. Proceedings of the National Academy of Sciences, April 2, 2012 DOI: 10.1073/pnas.1200130109
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