LIVE Pro & Con Debate: The Hot Topic in Clinical Research - Is sensory profiling with QST the appropriate procedure to identify the mechanisms that drive neuropathic pain? PRO

Quantitative Sensory Testing can assess multiple aspects of the sensory nervous system, including peripheral and central aspects, sensation and pain thresholds, and integrity of various pathways. Using comprehensive protocols in a standardized way, QST can thus paint a picture of the individual sensory alterations of each patient. Some of the emerging patterns have been linked to well-characterized surrogate models, indicating a link between patterns seen in patients and mechanistic studies. Although only few studies have been prospectively designed to test differential treatment response, the existing evidence points towards that specific treatments will be more efficient for patient groups with certain sensory patterns. It has also been shown that QST profiles change in response to worsening of the condition or improvement due to disease-modifying treatment. Thus, QST has demonstrated all elements of a biomarker: differentially responsive to treatment, linked to plausible mechanisms of disease, and responsive to changes in disease.

 LIVE Pro & Con Debate: The Hot Topic in Clinical Research Is sensory profiling with QST the appropriate procedure to identify the mechanisms that drive neuropathic pain? CON

Evoked pain responses are excellent tests to assess small fiber function and are highly valuable to diagnose small fiber neuropathy. Thus, in chronic pain patients QST is an important tool for the diagnosis of neuropathy. However, only a minority of patients with peripheral neuropathy develop chronic pain and therefore it is crucial to understand the mechanisms that differentiate between painful and painless neuropathy. Unfortunately, QST profiling does not contribute to this differentiation. Moreover, neuropathic pain patients with hyperexcitable nociceptors (NaV1.7 mutations) do not show a hyperexcitable nociceptor QST profile, whereas such a hyperexcitable nociceptor profile is found in the same percentage of about 10% in patients with strong neuropathic pain and painless neuropathy. These examples through serious doubts on the idea that QST profiles are linked to certain pain mechanisms. Recent data on painful carpal tunnel syndrome even found that QST thresholds in the neighboring non-affected skin are reversibly impaired by the ongoing pain; such impact of ongoing pain on QST results would even reverse the suggested mechanistic chain. Obviously, QST results do not correlate to the clinically most relevant ongoing pain and suprathreshold pain responses. In animal research, enormous efforts are being undertaken to generate parameters allowing quantification of ongoing pain and suprathreshold pain responses. We should avoid transferring the limitations from animal behavior to clinical research. Rather, we crucially need to develop and validate tests for phenotyping patients that correlate to clinically relevant aspects of their pain and suffering.

LIVE Panel Discussion/Q&A

Dr. Jan Vollert is a bioinformatician with a PhD in Neurophysiology from the Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Germany. His research focuses on the application of statistical and computational models in pain research, mainly in Quantitative Sensory Testing. He has conducted analyses of quantitative sensory testing data of patients suffering from neuropathic pain that have been largely acknowledged in the field.

He is a member of the International Association for the Study of Pain (IASP) and its Neuropathic Pain Special Interest Group, where he works on public outreach and trainee representation. He was invited speaker at congresses of the IASP, the NeupSIG, and the European Pain Federation. He published  over 50 peer-reviewed papers, and his h-index is 16.

Solomon Tesfaye is a Consultant Physician/Endocrinologist at Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield, UK. He qualified as a doctor at the University of Bristol in 1984 and trained in diabetes and diabetic neuropathy under Professor JD Ward. His research projects include the epidemiology, risk factors, pathogenesis, central nervous system involvement and treatment of diabetic neuropathy and neuropathic pain. He has published a book, over 150 original articles, reviews and book chapters in the field of diabetic neuropathy including a landmark study in the New England Journal of Medicine. He has received research funding from Diabetes UK, the US National Institute of Health (NIH), Juvenile Diabetes Research Foundation (JDRF), European Foundation for the Study of Diabetes and the UK National Institute for Health Research.

Professor Tesfaye was awarded the Prestigious Camillo Golgi Prize of the European Association for the Study of Diabetes (EASD) in 2014 for major scientific contributions in Diabetic Neuropathy. Professor Tesfaye has had international leadership roles including chairmanship of the International Expert Group on Diabetic Neuropathy that published 7 consensus recommendation papers in 2010/11, and of NEURODIAB (2006-9) which is the largest diabetic neuropathy scientific group in the world. He is also the current Vice Chairman of the Science and Research Committee of Diabetes UK; a Board Member of the Global Quantitative Sensation Testing Society; a member of the Advisory Council of the Neuropathy Trust and Secretary of International Insulin Foundation. He is currently the Associate Editor of Experimental Diabetes Research, Frontiers in Endocrinology, European Endocrinology and Diabetes Management and was previous Associate Editor of Diabetologia. Professor Tesfaye has served as a member of the JDRF, NIDDK, UK MRC and UK NIHR scientific review panels and as a member of a Diabetes & Neuropathic pain Review Group for the National Institute for Clinical Excellence (NICE).

Charles E. Argoff, MD, is professor of neurology and director of the Comprehensive Pain Program at Albany Medical Center in New York. Dr. Argoff received his medical degree from Northwestern University’s Feinberg School of Medicine in Chicago, Illinois. He completed an internship in the Department of Medicine and a residency in the Department of Neurology at the State University of New York in Stony Brook and a fellowship in developmental and metabolic neurology at the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS).

Dr. Argoff is a member of the International Association for the Study of Pain and the American Academy of Neurology, among other professional organizations. He has served as a guest editor for and published articles in the Clinical Journal of Pain and Current Pain and Headache Reports, among other peer-reviewed journals. Dr. Argoff had an active role in the development of the diabetic peripheral neuropathic pain guidelines published in Mayo Clinic Proceedings, and he has contributed to other published neuropathic pain treatment guidelines. He is one of the editors of the textbook Raj’s Practical Management of Pain, Fourth Edition. He has also published the third edition of Pain Management Secrets.

Neuropathic pain affects 7–10% of the population and is often ineffectively and incompletely treated. Although the gold standard for treatment of neuropathic pain includes tricyclic antidepressants (TCAs), serotonin-noradrenaline reuptake inhibitors, and anticonvulsants, patients suffering from neuropathic pain are increasingly turning to nonpharmacologic treatments, including nutritional supplements for analgesia. So-called “nutraceuticals” have garnered significant interest among patients seeking to self-treat their neuropathic pain conditions including disorders such as  diabetic neuropathy, chemotherapy related neuropathic pain, and fibromyalgia amongst many others with readily available supplements. The supplements most often used by patients include vitamins such as vitamin B and vitamin D, trace minerals zinc and magnesium, and herbal remedies such as curcumin and St. John’s Wort. However, evidence surrounding the efficacy and mechanisms of these supplements in neuropathic pain is limited, and the scientific literature consists primarily of preclinical animal models, case studies, and small randomized controlled trials (RCTs).  We will discuss the evidence behind the use of these agents as well as discuss needs for large randomized controlled trials to more fully inform patients and physicians on the utility of these supplements in neuropathic pain.

Kevin Hackshaw, M.D., is an associate professor and chief of the Division of Rheumatology in the Department of Internal Medicine.

Hackshaw is pleased to return to the state of Texas and is excited about the opportunities offered at The University of Texas at Austin and Dell Medical School. A native of Brooklyn, New York, he left NYC after graduating from Brooklyn College to attend Baylor College of Medicine. After four years in Houston, he returned to New York and trained in internal medicine at Harlem Hospital Center (Columbia University College of Physicians and Surgeons).

After three years of internal medicine, he served a year as chief resident at Harlem and then relocated for three years as a clinical research fellow in rheumatology at University of Colorado Health Sciences Center. His research focus in Denver was membrane biochemistry, and his initial areas of research interest involved focus on fatty acid metabolism in autoimmune murine models.

After completing his rheumatology fellowship, he accepted a faculty position at The Ohio State University in Columbus, joining the faculty in 1990. His basic research involved fatty acid membrane composition as it relates to promoting inflammation; molecular cloning and characterization of mouse acidic fibroblast growth factors; and evaluation of neurotrophins in experimental pain models with a specific focus on fibroblast growth factors. These studies were conducted over nearly two decades and supported by multiple National Institutes of Health, private foundation and pharmaceutical support.

Following these studies, Hackshaw evolved from utilizing experimental pain models to the human analogues of neuropathic pain, for which fibromyalgia is the prototypical disorder. His current NIH proposal seeks to develop reliable biomarkers that can be utilized to identify and characterize patients with fibromyalgia and hopefully provide a roadmap for identifying targeted therapies for this highly common but poorly understood disorder.

Hackshaw’s specialty interests are fibromyalgia, chronic pain, rheumatoid arthritis, systemic lupus erythematosus and vasculitis. His research interests center around the mechanisms of neurotrophins in propagating chronic pain states.

Time away from work is spent with his wife (Dawn Hackshaw, M.D., a pediatrician) and his children. Leisure pursuits include biking, exercising and avidly following New York Yankee baseball.

Professor Rainer Freynhagen is a specialist in anaesthesiology, intensive care, pain management, palliative care and sports medicine. He studied medicine in Germany, Switzerland and Great Britain and completed his studies 1992 at the Heinrich-Heine-University in Düsseldorf. After obtaining the status as Diplomate by the European Academy of Anaesthesiology and Intensive Care (DEAA) in 1999, he additionally completed a study in Health Management in Cologne in the following years.

For more than 10 years Professor Freynhagen led the Division of Pain Management and Palliative Medicine, Department of Anaesthesiology at the University Hospital Düsseldorf. In 2007 he was jointly awarded the Prize for Pain Research from the German Society for the Study of Pain (DGSS). Since April 2009 he is the elected head of the Department of Anaesthesiology, Critical Care Medicine, Pain Therapy & Palliative Care at the Benedictus Hospital Tutzing, Germany, an Academic Teaching Hospital of the Technical University Munich, which is at the same time one of the largest and renowned Pain Centres in Europe (Pain Centre Lake Starnberg). He holds his professorship, research and teaching assignment at the medical faculty of the Technische Universität München.

Professor Freynhagen is an elected member of the European Society of Anaesthesiology, member of the International Association for the Study of Pain and many other national and international scientific associations. He is specialized in the diagnosis and treatment of neuropathic pain, back pain and the fibromyalgia syndrome. His main research interests focus on pharmacologic mechanisms, treatment, epidemiology and phenotyping of neuropathic pain. He and his co-workers developed painDETECT, a worldwide used screening tool to discriminate between neuropathic and non-neuropathic pain.

Rainer Freynhagen serves as scientific grant reviewer for the Ministry of Health in several countries and an authorized expert for the German Federal Government. He has published numerous research articles, book chapters and reviews in different prestigious international top journals in the field of pain medicine, Anaesthesiology and palliative care and he has delivered globally several hundred invited scientific lectures.