Scientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Heidelberg University Scientists discover a metabolic poison which causes nerve damage:
Damage to the peripheral nerves is found in 60% of individuals with diabetes. Diabetic neuropathy paradoxically causes sporadic pain and increased sensitivity on the one hand, and impaired perception of external pain sources on the other hand. The scientists have now discovered one of the causes for impaired pain perception in an international research project: a naturally occurring metabolic poison which is produced in greater quantities in patients with diabetes and cannot be broken down effectively. The results of the study have now been published in the respected scientific Journal Nature Medicine.
“It is the long axons which supply the skin on the feet and hands as well as the stomach organs in particular that are damaged by diabetic neuropathy,” explains Prof. Dr. Susanne Sauer from the Institute for Physiology and Pathophysiology at FAU, who is one of the participants in the research project. “This causes paradoxical symptoms: the patient suffers from paraethesia such as ‘pins and needles’, feeling cold despite having warm skin, a burning sensation in the foot or cramp-like pain in the gastrocnemius muscle. Yet, at the same time, the patient becomes less able to perceive warmth and cold and their ability to feel pain caused by external sources declines. “Reduced perception of pain can be dangerous as the patient may not notice minor wounds which can develop into ulcers which do not heal properly as diabetes causes poor blood circulation.” This can lead to doctors having to carry out an amputation on the affected patient.
“The causes of nerve damage in diabetic neuropathy can be traced back to the increased blood sugar (glucose levels) but is not actually caused by the glucose itself,” explains Professor Sauer. Prof. Dr. Peter Nawroth’s team of diabetologists from Heidelberg University have shown that methylglyoxal, which is produced when glucose is broken down, is responsible for poisoning nerves. In healthy subjects, this enzyme is broken down and neutralised by the body. However, high levels of sugar in diabetic patients result in the increased production of methylglyoxal, which becomes more difficult to break down and thus accumulates and poisons nerves. This affects nociceptors, which were a particular focus of the research project of the team of researchers from Erlangen and their partners from Hanover and Bucharest.
Nociceptors are special axons which are found throughout the body for detecting potentially damaging external sensations which are triggered by thermal, mechanical or chemical influences. Nociceptors have several sensors and various sodium channels for this purpose. These sodium channels form nervous impulses which are transmitted to the brain to trigger a sensation of pain. “Methylglyoxal alters at least two of these sodium channels and impairs their function,” explains Prof. Dr. Susanne Sauer. “Methylglyoxal increases the receptivity of the axons by altering the biophysical properties of one of the sodium channels. This results in painful hypersensitivity, for example to thermal or mechanical stimuli.” In the other sodium channel, which is also found in the neurons in the autonomous nervous system, methylglyoxal reduces receptivity drastically. This could, among other things, also explain weaknesses in the stomach, intestinal, and bladder muscles in diabetic patients.
The diabetologists at Heidelberg University and FAU have discovered that methylglyoxal levels can be reduced therapeutically. Preliminary experiments have shown that artificial binding molecules (scavengers) can be used to fight pain for this purpose.
The international research project has been funded by several institutions including the German Research Foundation (DFG), the Juvenile Diabetes Research Foundation in the USA, the German Diabetes Association and the Alexander-von-Humboldt Foundation.
Prof. Dr. Susanne Sauer
sauer (at) physiologie1.uni-erlangen.de