New research: Morphine gets our wires crossed

Morpheus, the Greek god of dreams
 (pictured, fairly content, bottom left).
Guérin painted this picture in 1811,
six years before morphine was first sold
commerically.

Researchers may have found the cause of a mysterious side-effect of morphine.

Morphine, a drug used to treat chronic pain, is also known to cause inflammation of the central nervous system (CNS), reducing its pain-killing effects. The question is ‘how?’

In a study published in April in PNAS, Xiaohui Wang and colleagues demonstrated that morphine can directly trigger inflammatory signals in endothelial cells, which line the blood vessels carrying the drug to the CNS and the brain.

The team from  The University of California, San Francisco showed that morphine chemically attaches to a protein complex  made up of myeloid differentiation protein 2 (MD-2) and Toll-like receptor 4 (TLR4) on the surface of the cell. A chemical chain reaction carries a signal from the TLR4 receptor through the cytoplasm to the nucleus where pro-inflammatory genes are found in our DNA.

Inflammation is important for our cells in times of stress or injury. Tissues must change shape and structure, swelling with blood to enable the healing process to begin. But inflammation is an entirely unwanted side-effect after morphine treatment and ultimately demonstrates the body protecting itself against the pain-killer, rather than the cause of the pain.

The authors believe that by stopping morphine from attaching to MD-2 it's possible to increase the efficiency of morphine treatments and pain relief.

What does this mean for me?

The possibility of more effective pain killers in the future. The link between morphine treatment and inflammation in the CNS is also proposed to affect drug dependence leading to abuse.

What does this mean for science?

This is a great example of crossed wires inside the cell: on the way to the brain to trigger opiod receptors and numb pain, morphine sets off our inflammation receptors (in this case a combination of MD-2 and TLR-4 proteins*) which are sensitive to all sorts of "alien" chemcials. Similar crossed wires can cause some drugs to fail completely.

* Don't be put off by the names. Some are easier on the ear, there's even a protein called 'Sonic hedgehog'.

morphine cure advertisement circa 1900.
"The most remarkable remedy ever discovered"

Reference:

Wang, X., Loram, L., Ramos, K., de Jesus, A., Thomas, J., Cheng, K., Reddy, A., Somogyi, A., Hutchinson, M., Watkins, L., & Yin, H. (2012). Morphine activates neuroinflammation in a manner parallel to endotoxin Proceedings of the National Academy of Sciences, 109 (16), 6325-6330 DOI: 10.1073/pnas.1200130109