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“Nerves cannot be compared with telephone wires“

Neuropathic Pain: “Nerves cannot be compared with telephone wires“


Photo: Christian Maihöfner

Professor Christian Maihöfner; © private

Chronic neuropathic pain has many reasons and is often poorly diagnosed - at the same time, the origin of the pain has not been fully understood. Therefore scientific pain research has been trying to analyse specific neuropathic pain for some time. In this way, treatment options for chronic pain can be improved. In Europe, the USA and Japan 3.7 million people suffer from chronic neuropathic pain as a result of diabetes. asked pain researcher Professor Christian Maihöfner, senior physician at the University of Erlangen, Germany, how the research of this pain syndrome develops, which results are already on hand and which further issues have to be answered. Professor Maihöfner, how does neuropathic pain differ from other pain?

Christian Maihöfner: Neuropathic pain can develop after injuries and affections of the peripheral or central pain conducting system. Nociceptive pain, where the peripheral and central structures of pain conduction are intact, needs to be distinguished from this. Patients for the most part perceive neuropathic pain as very severe and describe it with attributes such as electrifying, tingling and burning. Neuropathic pain is typically limited to one nerve innervation area. After a stroke for example this often is hemiplegic pain. Is the origin and development of this pain in the body already well known in research?

Maihöfner: We were able to gain amazing findings in research over the past few years. We have learned for instance that nerves cannot be compared with telephone wires. This means: if nerves are injured, they are not silent, but instead often start to spontaneously fire. They react more sensitively to heat or mechanical stimuli. By now we also understand the complex mechanisms that play a role in the pain transmission in the spinal cord. In addition, certain cell types (so-called glial cells) can influence the pain experience. The mosaic of mechanisms is therefore large. Nonetheless, until now we have only inadequately understood the large variability of neuropathic pain. Some patients who suffer from nerve damage or polyneuropathy, can develop neuralgia (nerve pain), while others do not. So far we have only insufficiently comprehended this. This probably in part has still unclear genetic causes. What triggers for these pains are the focus of your nationwide German research project?

Maihöfner:On the one hand we are researching the peripheral causes, for example pain from diabetes mellitus, zoster neuralgia, traumatic nerve injury or the so-called complex regional pain syndrome (CRPS). On the other hand, the central nervous system can be affected, particularly in the case of a spinal cord injury. In stroke cases, neuropathic pain occurs through the destruction of brain structures.

Photo: Neural cells

Scientists particularly measure how the functions in terms of neuropathic pain have changed for the individual patient; © krishnan In the scope of this research project, patients are categorized into different neuropathic pain syndromes. How exactly does this analysis take place?

Maihöfner: In this case we try to understand the function of the different nerve fibers. We particularly measure how the functions in terms of neuropathic pain have changed for the individual patient. During the research we use natural stimulus materials. Our test is therefore made up of a thermal and a mechanical part. During the thermal part we determine the hot and cold sensitive spots. In the mechanical part we pay attention to the tactile detection thresholds.

Here the main focus is on the relative touch sensation and the mechanical pain threshold. We check whether the patients experience pain during a soft touch, this meaning they have developed so-called allodynia and whether hypersensitivity to pressure and vibration stimuli can be detected. In doing so we can specifically determine which part of the nervous system is affected in its function. The interconnections of pain sensation, for example the complex regional pain syndrome (CRPS), are not entirely deciphered yet. Which findings are currently being discussed?

Maihöfner: One aspect that’s being discussed is that an abnormally increased inflammatory tendency, a so-called neurogenic inflammation plays a role in the peripheral nervous system. An interconnection between the sympathetic nervous system and the pain conduction system could also be possible. The latest theories hold central changes in the nervous system responsible for the disease. This includes changes of particular body maps in the brain that make it possible to explain the complex, sensitive and motor malfunctioning as well as the neglect symptomatology. Herpes zoster, commonly known as shingles, can cause postherpetic neuralgia (PHN). What makes this disease so special with regard to neuropathic pain?

Maihöfner: In many authorization safety studies for new drugs in the field of neuropathic pain, an analysis is made for patients with postherpetic neuralgia. Herpes zoster is an inflammatory neuropathy. Three mechanisms can cause pain in this case: the patient can develop a loss of nerve function, since areas of the system for pain conduction are destroyed by infection. Other patients show symptoms of nerve hypersensitivity and react significantly more to pressure to the skin, warmth and heat stimuli. The third subgroup show symptoms of central sensitization, i.e. they sense light touch stimulus as being painful.

Photo: Brain regions

In the future the scientists would like to study what functions the different brain regions of pain processing assume in chronic pain; © Paul Hakimata In your research study imaging techniques play an important role. Which findings were you already able to derive from your analysis?

Maihöfner: We were particularly able to observe that one and the same pain stimulus can be unbelievably dynamically processed. This is fascinating. At this point, imaging techniques provide us with detailed insights into the central mechanisms of neuropathic pain, the change of body maps like for instance in the case of complex regional pain syndrome (CRPS) or phantom pain. Normally our entire body scheme is stored in a single convolution of the brain – and precisely this representation can be distorted with neuropathic pain. In addition we have modulating brain networks, which can decrease or also increase pain. In the case of neuropathic pain these networks appear to malfunction. What will research look like in the future?

Maihöfner: In the future we would especially like to study what functions the different brain regions of pain processing assume in chronic pain. Alongside that we have learned by now how therapy treatments with or without drugs can strongly influence central pain processing. Since pain is differently perceived in different contexts, we have to also increasingly incorporate these new findings into multimodal therapy for patients suffering from chronic pain.

The interview was conducted by Diana Posth and translated by Elena O’Meara.