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Tuesday, November 20, 2012

On the trail of chronic pain


NaV1.7 is a voltage-gated sodium channel. This means that it’s a group of transmembrane proteins that together form a tunnel through which sodium ions can pass. The passage isn’t open all the time though. Only a localized difference in electrical potential (voltage) will open the gate, allowing sodium ions to enter the cell from the outside. This, in turn, alters the microenvironment of the next stretch of membrane. In this way, a signal is rapidly propagated along the length of the cell. Each type of ion can only enter a cell through a matching ion channel (sodium ions through sodium channels, potassium ions through potassium channels, etc). What makes NaV1.7 special is that it’s associated with the sensation of pain.



























Diagram of ion channel.
Credit Sandwalk.

If your NaV1.7 channels are inactive (permanently closed) you might not feel any pain at all (which is a lot worse than it seems). If the channels are overactive (unable to close) you’ll have chronic pain. This is the case for the unfortunate sufferers of a condition called inherited erythromelalgia, a.k.a. ‘Man on Fire Syndrome’. You can guess how that feels. To make things worse, some varieties of NaV1.7 channels do not respond well to medicines designed to stabilize ion channels.

Yang Yang and her colleagues from Yale University School of Medicine were able to study the effects of specific mutations within the NaV1.7 channels that render them more or less sensitive to pain medicines. Apparently, genotype does make a significant difference in how well people will respond to treatment. The scientists suggest that chronic pain patients routinely have their ion channels screened for subtype as a part of their treatment regimens. This may lead to the illusive cure for at least some types of chronic pain.

Yang, Y., Dib-Hajj, S., Zhang, J., Zhang, Y., Tyrrell, L., Estacion, M., & Waxman, S. (2012). Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel Nature Communications, 3 DOI: 10.1038/ncomms2184