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Pain is usually caused by inflammation in the body. Scientists from the University of Würzburg have now demonstrated that one of the responsible substances simultaneously has a pain-relieving function. Their discovery is a promising target for new therapy.
Pain is one of the five typical symptoms of inflammation. This type of pain is caused by special inflammatory substances that sensitise nerve cells in the affected tissue. Subsequently, the nerve cell transmits an enhanced electrical signal to the brain where it triggers the pain sensation. In fact, however, the process is much more complex than previously thought.
Scientists from the University of Würzburg have now established that these inflammatory substances not only cause pain. Professor Erhard Wischmeyer, PD Dr. Frank Döring and biologist Sina Kollert of the university's Institute of Physiology have demonstrated that the substances simultaneously activate a second type of channel in the walls of nerve cells and in doing so counteract the emergence of pain. The scientists present their work in the journal Scientific Reports.
Potassium channels play a key role
"The excitability of nerve cells is essentially regulated by the activity of potassium channels," Frank Döring explains the underlying principle. The more potassium ions leave the cell through these channels, the less sensitive the cell is towards external or internal stimuli. The same applies to the so-called nociceptors, the sensory neurons for pain stimuli. Their potassium channels are crucial to balancing the excitability.
The research activities of the Würzburg physiologists centre on a specific potassium channel, called TRESK in medical lingo. They found in previous studies that this channel is particularly abundant in sensory neurons. Using a newly developed antibody, they have successfully proved now that the TRESK channel is localised both in the cell body and in the nerve fibres that reach into the surface of the skin. "This places the TRESK channel in the direct vicinity of the so-called TRP channels that have been known to be pain receptors for quite some time," Döring further.
An equilibrium between excitation and inhibition
What makes the adjacency of two different channels so important from a medical point of view: "If there is an inflammation, substances will build up in the affected tissue that activate just these TRP channels and thereby initiate pain processes. But at the same time, they also activate the TRESK channels and make sure that the signals responsible for pain development are dampened significantly," Döring explains. Accordingly, the sensory neurons of mice in which the TRESK channel is missing react much more strongly when in contact with an inflammatory mediator than normal cells. "The TRESK channel has a dampening effect on the excitation of sensory neurons and thus protects the processes of peripheral pain development," the scientists conclude.
Connection to migraine
According to the Würzburg physiologists, their findings and conclusions are in line with the discovery that people having a mutation in the gene for the TRESK channel regularly suffer from migraine attacks with sensory symptoms. The role inflammatory processes in the brain play in migraine is the subject of the present scientific discourse. However, the new study has all but proven that the TRESK channel is a new important target protein to develop improved medication for treating different types of pain.
Activation of TRESK channels by the inflammatory mediator lysophosphtidic acid balances nociceptive signalling. Kollert S., Dombert, B., Döring, F., Wischmeyer, E. Scientific Reports, online 30.07.2015
Contact
Prof. Dr. Erhard Wischmeyer, Phone: +49 931 201-77531; E-mail: e.wischmeyer@uni-wuerzburg.de
PD Dr. Frank Döring, Phone: +49 931 201 77532; E-mail: fdoering@uni-wuerzburg.de
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