Neuropathy Research In Germany

Today's post from neuro.med.tu-muenchen.de (see link below) is a technical one, in that it uses language with which not everyone will be familiar. However, it does show the sort of research that is being done in the field of neuropathy across the world and how solutions are being seriously investigated in every area of the disease. Five million people are affected by neuropathy in Germany (roughly 6% of the population) and that just goes to show how widespread a medical problem it is (20 million in the United States) and yet only now is the medical world seemingly waking up to the fact that this is a world-wide problem.

German Research Network On Neuropathic Pain
Pathophysiology, prevention and therapy
Friday, 15. February 2013: German Research Network on Neuropathic Pain
Speakers: R.Baron and T.R. Tölle

Classification of neuropathic pain has been based on disease entities, anatomical localization and histological observations. Treatment algorithms have been almost entirely empirical and disease-oriented. In the past decade, studies in animals and humans have shown that neuropathic pain is probably not a result of a single pathophysiological mechanism, but the end product of an altered peripheral, spinal and supraspinal processing. Since sensory symptoms and special pain types are closely related to the underlying mechanisms, clinical assessment of the symptoms can give a clue of the distinct mechanisms that operate in one individual patient.

The main concept of the German Research Network on Neuropathic Pain (DFNS) focuses on the idea of a mechanism-based and symptom-oriented approach of neuropathic pain. In order to derive a more rational treatment of neuropathic pain, the DFNS proposes the following strategy:
to establish a data base of patients including psychological and quantitative sensory evaluation,
to define pathophysiological mechanisms of pain and associated symptoms as well as the development of chronic neuropathic pain,and
to introduce new and to evaluate available interventions to prevent and treat neuropathic pain on the basis of a mechanism-based and symptom-oriented approach.

Germany has already developed a solid international reputation in basic as well as clinical research on neuropathic pain. The DFNS fosters research in the field of neuropathic pain by integrating the resources of the leading centers in Germany actively involved in neuropathic pain research. Since its foundation in 2002 the DFNS is funded by the German Federal Ministry of Education and Research (BMBF).

The central Integrative Network Project of the German Research Network on Neuropathic Pain is a Neuropathic Pain Data Bank. All network participants subserve the data bank with standardized information of each patient regarding socio-economic, psycho-social, psychological data and results of quantitative sensory testing (QST). Moreover, a blood sample and imaging data bank have been initiated. The data is centrally coordinated by a data management system for documentation and quality assurance.

Patient variables are used for epidemiological, cost-effectiveness and cost-utility analyses, symptom description in relation to disease entities, psychological co-morbidity and stratification for one Primary and one Secondary Prevention Study. In these multicenter-studies the efficacy of several compounds in preventing and treating chronic neuropathic pain will be evaluated. Based on current evidence, the RC-trials have now been focused on pregabalin, NMDA-antagonists and opioids.

Furthermore, the data bank gives access to patients to be investigated in Special Network Projects. Suitable patients with particular profiles of pain and sensory symptoms are included and exchanged between all Special Network Projects to assess pathophysiological mechanisms. On this research level three subgroups have been established that comprise complementary and overlapping fields of interest:
Pathophysiological mechanisms after compression, degeneration and regeneration of peripheral nerves
Central integration of nociceptive processing
Physiological and psychological influences on cortical reorganisation in complex regional pain syndromes

Overall, the integration of research and service will improve the understanding of the pathophysiology and foster the development of new and the appropriate usage of established interventions for the treatment and the prevention of neuropathic pain. The ultimate goal is to prevent the development of chronic pain by an early intervention or to extinguish chronic pain by a thoughtful combination of multiple treatment options.

The German Research Network on Neuropathic Pain (DFNS) includes the major institutions, authorities and medical disciplines engaged in therapy and research on neuropathic pain. The central Integrative Network Project of the DFNS is a Neuropathic Pain Data Bank. Virtually all network participants (interdisciplinary pain clinics, clinical research, basic science research) subserve the data bank with standardized information including more than 500 parameters of each patient/ volunteer regarding socio-economic, psycho-social and psychological data as well as results of quantitative sensory testing (QST) in order to describe the variety of symptoms and the underlying mechanisms as precisely as possible. A standardized and comprehensive QST protocol was successfully developed and implemented during the first year of the DFNS funding. Till July 2007 about 1200 neuropathic pain patients have been tested with this QST battery and enclosed in the Neuropathic Pain Data Bank. In order to have data for comparison QST reference values from about 180 healthy volunteers from 10 participating centers have been obtained.

Moreover, a blood sample bank and an imaging data bank have been initiated. All clinical data are centrally managed by a data management system for documentation and quality assurance in pain treatment (QUAST "Qualitätssicherung in der Schmerztherapie"). Beside permanent access to the central data bank, every participant is supplied with a local data management system (QUAST) for monitoring the individual data base.

This approach allows:
to delineate epidemiological data from a high number of patients,
to stratify patient variables for Primary and Secondary Prevention Studies,
to lend access to patients with particular profiles of pain and sensory symptoms from other centers and
to deduce the representativeness of patient/ volunteer collections investigated in Special Network Projects in comparison to the whole study population.

The Special Network Projects cooperate (horizontal networking). Additionally, participants at the research level cooperate in varying intensity with the service level (data collection-level, prevention study-level) depending on the particular scientific task (vertical networking). The objective of top-down and bottom-up information flow is continuously examined by the Network Board to assure early strategy changes in data collection or research planning. The participants working together on Integrative and Special Network Projects are coordinated by the Network Board involving the speakers of DFNS and the principal investigators of the Special Network Projects as well as representatives of the cooperating partners involved at the service level (Interdisciplinary Pain Clinics).

Beyond the coordination of Integrative and Special Network Projects, the Network Board deals, supported by the Network Head Office, with principal network subjects, such as internal quality management, contact to other pain networks, health economy, public relations, postgraduate training, medical education and relations to industry.

The participants of the Integrative Network Projects represent major Interdisciplinary Pain Clinics with a long-standing experience in the management of neuropathic pain patients. The centers are located at Universities as well as Municipal and Rehabilitation Hospitals all over Germany.

At the service level, many of these centers treat between 300 to 1000 new outpatients with acute and chronic pain a year, a huge number of them presenting with neuropathic pain. Horizontally, all of the centers have contacts with a broad group of general practitioners, which will further support the recruitment of study patients to a considerable extent upon request.

All participants use standardized patient inventories (somatic, psychological), apply a standardized battery for "Quantitative Sensory Testing" (QST) and are trained for adequate usage. All basic science researchers (see Special Network Projects) have access to the same instruments, either from own resources, or through their local Interdisciplinary Pain Clinics.

The structure of GNNP allows to achieve maximum synergism between basic research and clinics, provides ample interaction between multiple clinical disciplines and, together with the fact of participating centers all over Germany, will guarantee a straight-forward transfer into clinical practice in the whole country.

Neuropathic pain is defined as a pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Several traumatic, inflammatory, ischemic and metabolic disorders can cause nerve damage and lead to neuropathic pain. The most frequent neuropathic pain states are painful diabetic neuropathy, acute herpetic and postherpetic neuralgia, phantom limb pain, central post stroke pain as well as complex regional pain syndromes. Neuropathic pain tends to be chronic. It frequently results in a burning, ongoing and shock-like sensation. Neuropathic pain can be associated with negative sensory symptoms (like hypoesthesia or hypoalgesia) as well as with positive ones (e.g. allodynia or dysesthesia).

6 percent of the German population suffer from neuropathic pain, that affects about 5 million people. Furthermore in Germany, in specialized pain clinics about 20% of all pain patients present with previously insufficiently controlled symptoms of neuropathic pain. Patients with neuropathic pain are seen for their symptoms by 8 different doctors on average over a period of ten years and are hospitalized for 72 days during this time. A recent survey on pain medicine education among American neurologists revealed that only 30% of practicing neurologists felt adequately trained to diagnose and 20% to treat pain disorders. A German survey among neurologists on the structures and standards of evaluation showed that only 22% performed a standardised evaluation of somatic aspects of pain, whereas psychic aspects are assessed in not more than 15% of the departments.

In economic terms, there are no estimations of the direct, indirect and intangible costs. The prevalence of neuropathic pain and the long-lasting, intensive use of medical services make it reasonable to suggest that diagnosis and treatment of neuropathic pain occupies considerable medical resources and creates substantial costs.

The current treatment algorithms of neuropathic pain take into consideration (1) to cure the original cause of the pain, (2) to achieve complete or at least partial analgesia by pharmacological and non-pharmacological strategies and (3) to improve pain coping by psychological treatment strategies. Traditionally pharmacological studies have been directed towards a specific disease entity rather than specific signs or symptoms. Management of patients based on their disease state, however, is probably not the most effective way to address specific neuropathic pain signs and symptoms.

Various different pathophysiological mechanisms can coexist in one disease entity in various combinations and may also be present in one single individual. Thus, drug regimens should be targeted towards the underlying mechanism responsible for the observed and reported findings. For example, patients with allodynia would be expected to respond to similar treatment, although the pathogenesis giving rise to it may reflect a multitude of diverse disorders such as diabetic neuropathy, post-herpetic neuralgia, or nerve entrapment. This approach is appropriate since precipitating changes in the nervous system would be expected to be similar for those suffering from allodynia and therefore therapy should likewise be comparable.

Thus it is an important step to establish a future mechanism-based drug therapy of neuropathic pain. If it would be possible to characterize the concert of the distinct mechanisms that operate in one individual patient, an optimal polypharmacotherapy that addresses the specific combination of mechanisms may be established for each patient. This concept is realized in the development of the Neuropathic Pain Data Bank of the DFNS: it defines neuropathic pain symptoms - independent of the etiology - and will then proceed to treat these symptoms with combinations of various substance classes.

http://www.neuro.med.tu-muenchen.de/dfns/uns/e_portrait.html#oben