Researchers from Erlangen and Munich detect causes of painful nerve disorder
Cancer patients who are administered the drug Oxaliplatin during chemotherapy often suffer from painful nerve disorders. Researchers from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and LMU Munich have now detected the cause of this severe side effect. They recently published their results in the journal PNAS and received the German Association for the Study of Pain’s first prize in the category ‘fundamental research’.
Oxaliplatin is a drug that is used in colon cancer therapy, among other things. One of its frequent side effects is both an acute and a chronic form of nerve damage, which may be so severe that therapy has to be discontinued. The muscle cramps and extremely unpleasant sensations – a kind of tingling feeling – occur as soon as patients touch a cold object such as a beverage can. As a result, patients avoid cold drinks and low room temperatures since the effects, which can occur in all parts of the body, are unbearable. In the study, FAU scientist PD Dr. Angelika Lampert from the Institute for Physiology and Pathophysiology and her Munich colleague Dr. Ruth Sittl, assisted by their respective teams, show which part of nerve cells is responsible.
In human neurons information is transmitted in the form of electrical impulses, e.g. in the sodium channels. At one of these channels, the voltage-sensitive sodium channel of the subtype 1.6 (Nav1.6), the drug causes the erroneous transmission of impulses – which produces the symptoms from which patients suffer. The effect is increased when nerve fibres are cooled down during treatment with Oxaliplatin: when patients touch a cold object, the normal skin temperature of 32 C° temporarily falls to 22 C°, which means that even more impulses are transmitted and the painful symptoms become more intense. In an experiment, the researchers studied mice that do not have a functional Nav1.6 channel. They found that Oxaliplatin did not lead to more impulses irrespective of temperature. They concluded that the symptoms can be effectively treated by an active agent that blocks the sodium channel.
If the scientists succeed in developing this kind of agent, the often lifesaving chemotherapy treatments will no longer have to be discontinued because of severe side effects. At present the researchers are studying the molecular basis of this characteristic of the sodium channel to lay the foundation for the development of new therapeutic agents.
PD Dr. Angelika Lampert
Phone: +49 (0)9131 85 22888