Pain May Have an Off Switch

July 19, 2012 § Leave a comment

Chemists at LMU Munich have collaborated with colleagues at Berkeley and Bordeaux to perform a series of lab experiments on pain inhibition and pain-sensitive neurons. They have discovered something like a pain switch, allowing the inhibition of the activity of pain-sensitive neurons. Findings were published in February of this year in Nature Methods. The researchers were able to use an agent that acts as a photosensitive switch for the pain sensation. The LMU team, led by Dirk Trauner, Professor of Chemical Biology and Genetics at LMU, developed a system involving a chemical compound called QAQ.

QAQ is a bi-part molecule, with each part containing a quaternary ammonium, connected by a nitrogen double bond (N=N). The bridge between this bond is the pain switch. It is sensitive to light in that when irradiated with light of a certain wavelength, the molecule will flip from a bent to an extended shape. When treated with light of a different color, the effect is reversed.

One of the halves of QAQ resembles Lidocaine, a local anesthetic used by many dentists. The receptors of certain nerve cells in the skin that respond to painful stimuli and transmit signals to the spinal cord are blocked by lidocaine. Neuroreceptors are proteins that cover the outer membrane of nerve cells. They contain pores that open in response to certain stimuli to regulate the flux of electrically charged ions in and out of a cell. The conduit targeted by the lidocaine-like half of QAQ reacts to heat by permitting positively charged sodium ions to enter the cells that come to express it. This changes the electrical capability across the membrane, which conducts the transmission of the nerve impulse.

The researchers conducted an animal experiment, making use of QAQ’s ability to percolate through endogenous ion channels to transfer a molecule into a nerve cell. They would irradiate the lidocaine-like end of QAQ with a 380-nm light, causing the bridge between them to bend. They would then expose it to light with a 500 nm wavelength and the molecule would return to its extended form and reinstate its inhibitory action.

The researchers regard this new irradiation method as a great tool for neurobiological studies, especially for pain research. Timm Fehrentz, one of Dirk Trauner’s PhD students, says that therapeutic applications of this principle are, “a long way off.” One problem to overcome is the fact that the monochromatic light used to isomerize the QAQ molecules does not penetrate through human skin deep enough to reach the neurons, therefore researchers are looking into lights of longer wavelengths.

 

Works Cited

 

“An Off Switch For Pain”. (February 22, 2012). Neuroscience News. March 2, 2012. http://neurosciencenews.com/light-controlled-neural-inhibitor-off-switch-pain/.

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