Ralf Baron's research while affiliated with University Medical Center Schleswig-Holstein and other places

Publications (364)

Article
Treatment of neuropathic pain remains inadequate despite the elucidation of multiple pathophysiological mechanisms and the development of promising therapeutic compounds. The lack of success in translating knowledge into clinical practice has discouraged pharmaceutical companies from investing in pain medicine; however, new patient stratification a...
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Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (i.e., “precision pain medicine”). Precision pain medicine, currently an aspirational goal, would consist of empirically-based algorithms t...
Article
Treatment of neuropathic pain (NP) is challenging. Interest in real-world evidence (RWE) for benefit-risk assessments of NP treatments increases given the paucity of drugs showing efficacy in randomized controlled trials and restricted labels of available medicines. To provide further context, a literature review regarding regulatory use of RWE and...
Preprint
BACKGROUND Turning during walking is a relevant and common everyday movement and it depends on a correct top-down intersegmental coordination. This could be reduced in several conditions (en-block turning), and lead to increased risk of falls. Smartphone use has been associated with poorer balance and gait, however its effect on turning-while-walki...
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Neuropathic pain causes substantial morbidity and healthcare utilization. Monotherapy with antidepressants or anticonvulsants often fails to provide relief. Combining different drugs sometimes provides improved analgesia and/or tolerability. Over half of patients receive 2 or more analgesics and combination trials continue to emerge. This review co...
Article
Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus...
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Hereditary transthyretin amyloidosis is caused by pathogenic variants (ATTRv) in the TTR gene. Alongside cardiac dysfunction, the disease typically manifests with a severely progressive sensorimotor and autonomic polyneuropathy. Three different drugs, tafamidis, patisiran, and inotersen, are approved in several countries, including the European Uni...
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Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype...
Article
Objective We aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system. Methods In order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were sync...
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Healthy adults and neurological patients show unique mobility patterns over the course of their lifespan and disease. Quantifying these mobility patterns could support diagnosing, tracking disease progression and measuring response to treatment. This quantification can be done with wearable technology, such as inertial measurement units (IMUs). Bef...
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Background and Objectives Reduced laser evoked potential (LEP) habituation indicates abnormal central pain processing. But the paradigm (4 stimulation blocks a 25 stimuli) is time-consuming and potentially omits important information on the exact habituation time course. This study examined whether a high temporal resolution (HTR) analysis (dividin...
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Cancer diagnosis and treatment are drastic events for patients and their families. Besides psychological aspects of the disease, patients are often affected by severe side effects related to the cancer itself or as a result of therapeutic interventions. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurologic...
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Objective For many medical professionals dealing with patients with persistent pain following spine surgery, the term failed back surgery syndrome (FBSS) as a diagnostic label is inadequate, misleading and potentially troublesome. It misrepresents causation. Alternative terms have been suggested but none has replaced FBSS. The International Associa...
Article
There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for “precision medicine” or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment...
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Pregabalin is one of the first-line treatments approved for the management of neuropathic pain (NeP). While many patients benefit from treatment with pregabalin, they are often treated with suboptimal doses, possibly due to unfamiliarity around prescribing the drug and/or side effects that can occur with up-titration. This narrative review discusse...
Article
To ensure an adequate pain therapy with high patient adherence, it is necessary to know and consider patient preferences. A discrete choice experiment (DCE) was used to obtain patients’ preferences regarding treatment with systemic or topical pain medication. Patients with peripheral neuropathic pain (pNP) were recruited in two pain‐focused practic...
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Background Localised Neuropathic Pain (LNP) is challenging to diagnose and manage in primary care. Objective To describe clinical characteristics, treatment patterns, quality of life and sleep performance of patients with LNP and estimate its prevalence in primary care. Methods Cross-sectional study in 4 European countries. Patients were identifi...
Article
The pathophysiology of pain in neuropathy is complex and may be linked to sensory phenotypes. Quantitative sensory testing, a standardized method to evaluate sensory profiles in response to defined stimuli, assesses functional integrity of small and large nerve fiber afferents and central somatosensory pathways. It has revealed detailed insights in...
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Central disinhibition (CD), as applied to pain, decreases thresholds of endogenous systems. This provokes onset of spontaneous or evoked pain in an individual beyond the ability of the nervous system to inhibit pain resulting from a disease or tissue damage. The original CD concept as proposed by Craig entails a shift from the lateral pain pathway...
Article
Die Synkope ist eine plötzlich eintretende, kurzzeitige Bewusstseinsstörung mit Tonusverlust, die ohne weitere Intervention vollständig reversibel ist. Eine Abgrenzung von anderen kurzzeitigen Veränderungen des Bewusstseins wie bei Epilepsien, Durchblutungsstörungen des Hirnstamms, metabolischen Störungen, Intoxikationen, psychogenen Anfällen und t...
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PurposeFabry disease frequently includes pain as an early disease feature, which was characterized as a dysfunctional processing of somatosensory information in various studies. The pathomechanism involves the mutation in the x-chromosomal GLA-gene and a consequent reduction of the α-galactosidase. This results in an insufficient reduction of globo...
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Introduction: Stratification of patients according to the individual sensory phenotype has been suggested a promising method to identify responders for pain treatment. However, many state-of-the-art sensory testing procedures are expensive or time-consuming. Objectives: Therefore, this study aimed to present a selection of easy-to-use bedside de...
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Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson’s disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly fre...
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To investigate sensory changes, physical function (pF), quality of life (QoL) and pain intensity of patients with osteoarthritis (OA) in the natural course of disease, and patients undergoing total joint replacement therapy (TJR) 31 (20 females, mean age 64.6 ± 10.4 years), patients with OA were investigated with questionnaires and quantitative sen...
Article
Background and aims: Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entit...
Article
Aim To investigate whether the self-treatment of migraine among neurologists and pain specialists corresponds to national medical guidelines and treatment of patients. Methods An email cross-sectional survey was sent to members of the German Society for Neurology, German Pain Society and German Migraine and Headache Society containing questions on...
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Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative...
Article
Neuropathic pain (NeP) can result from sources as varied as nerve compression, channelopathies, autoimmune disease, and incision. By identifying the neurobiological changes that underlie the pain state, it will be clinically possible to exploit mechanism-based therapeutics for maximum analgesic effect as diagnostic accuracy is optimized. Obtaining...
Chapter
Synopsis Neuropathic pain is a common disease characterized by both positive (hyperalgesia) and negative (hypesthesia, hypoalgesia) somatosensory symptoms and signs. Numerous pathophysiological mechanisms are involved in the development of neuropathic pain. Therapeutic options are often insufficient due to common adverse events and limited efficacy...
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Purpose: Allodynia refers to pain evoked by physiologically innocuous stimuli. It is a disabling symptom of neuropathic pain following a lesion within the peripheral or central nervous system. In fact, two different pathophysiological mechanisms of cold allodynia (ie, hypersensitivity to innocuous cold) have been proposed. The peripheral sensitiza...
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Purpose: High dose monotherapies or drug combinations are used to achieve sufficient analgesia for the treatment of severe chronic low back pain, before invasive therapy options are considered. In order to demonstrate an alternative for an empirical treatment approach, the authors' primary aim was to present an algorithm for the objective identific...
Chapter
Schmerzen sind im Akutstadium eine protektive Reaktion des Körpers, um sich vor potenziellen Gewebeschädigungen zu schützen. An dieser protektiven Reaktion sind sowohl sensorische Afferenzen als auch somatische und vegetative motorische Efferenzen beteiligt. Daneben spielen assoziierte kognitive, affektive und endokrine Komponenten eine Rolle. Akut...
Chapter
Chronische neuropathische Schmerzen sind in der klinischen Praxis häufig. Sie stellen eine großes ökonomisches Problem im Gesundheitswesen dar und führen meist zu einem enormen Leidensdruck der Patienten. Die Prävalenz neuropathischer Schmerzen in der Bevölkerung liegt bei ca. 5 %. Die Therapie sollte, wenn möglich, kausal erfolgen. Häufig ist jedo...
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Purpose: Fabry disease belongs to lysosomal storage disorders and can be successfully treated today. On the contrary, the correct diagnostic classification of its symptoms can be challenging and most patients suffer from pain for years, until they are diagnosed correctly. The aim of this project was to characterize patients with unclassified extre...
Article
Hyperalgesia and allodynia are frequent in neuropathic pain. Some pain questionnaires like the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and the Neuropathic Pain Scale (NPS) include self-assessment or bedside-testing of hyperalgesia/allodynia. The aim of this study was to determine to what extent LANSS and NPS data are congruent wi...
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Background Previous studies investigated cold‐evoked potentials (CEPs) for the assessment of the integrity of cold mediating A‐delta fibres and the spino‐thalamic tract. Nevertheless, several methodological questions remained unanswered to proceed to clinical application. How do latencies and amplitudes vary between CEPs and contact heat evoked pot...
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Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in...
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Introduction Multiple mechanisms are involved in the development and persistence of neuropathic pain. Some patients with nerve damage will remain painless and develop a “loss of function” phenotype, whereas others develop painful neuropathies. Objectives The aim of this study is to investigate the role of a peripheral nervous system sensitization...
Chapter
Neurogeriatrische Patienten mit Schmerz als Komorbidität werden häufig nur unzureichend behandelt. Eine gezielte Schmerzdiagnostik und -therapie wird besonders anspruchsvoll, wenn kognitive Fähigkeiten eingeschränkt sind. Im diagnostischen schmerzmedizinischen Fokus steht eine strukturierte Anamnese, welche gemäß ICF-Modell zusätzlich zu Organ-bezo...
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The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary...
Article
Peripheral neuropathic pain is among the most prevalent types of neuropathic pain. No comprehensive peripheral neuropathic pain classification system that incorporates contemporary clinical, diagnostic, biological, and psychological information exists. To address this need, this article covers the taxonomy for 4 focal or segmental peripheral neurop...
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Introduction In postherpetic neuralgia (PHN) different types of patients can be distinguished regarding their predominant peripheral nociceptor function. Objective The aim was to examine somatosensory profiles in the course of disease with special regard to the different subtypes existing in PHN. Methods Twenty patients with PHN (7 men and 13 wom...
Article
Patients with postherpetic neuralgia may experience various sensory signs and symptoms of pain. Despite this, the recommendations for medicinal treatment do not differ accordingly. In order to find the appropriate treatment options for postherpetic neuralgia, several attempts have been made in the past. The crucial obstacle to these attempts was in...
Article
Pain sensitivity is characterized by inter-individual variability, determined by factors including genetic variation of nociceptive receptors and pathways. The sigma-1 receptor (SIGMAR1) is involved in pain modulation especially under pre-sensitized conditions. However, the contribution of SIGMAR1 genetic variants to pain generation and sensitivity...
Article
Neuropathische Schmerzen sind durch eine Vielzahl positiver und negativer somatosensorischer Symptome der Patienten gekennzeichnet. Dazu zählen beispielsweise thermische und mechanische Hypoästhesie, Hypo- oder Hyperalgesie sowie Allodynie. Derlei Symptome können anamnestisch erfragt und mittels der klinisch-neurologischen Untersuchung oder auch st...
Article
Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here we analyze time-dependent changes in estimated tr...
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Purpose of review: It has been demonstrated that within one pain entity, patients may report highly heterogenic sensory signs and symptoms. Although mechanism might differ fundamentally between those patients, yet the treatment recommendations are uniform throughout all phenotypes. Therefore, the introduction of new stratification tools could pave...
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PurposeNegative cerebrovascular effects can be expected by compressing jugular veins and carotids by a necktie. It was already demonstrated that a necktie increases intraocular pressure. In many professions, a special dress code including a necktie and a collared shirt is mandatory although little is known about the effect of this “socially desirab...
Article
Here, we examine the stark contrast between the successes and failures of the clinical development of analgesics for different types of chronic low back pain (CLBP) syndrome over the past three decades. Multiple drugs with differing mechanisms of action have been developed for nonspecific axial-predominant low back syndromes and yet not a single th...
Article
Background: Fabry disease, an inherited lysosomal storage disorder, causes multi-organ pathology resulting in substantial morbidity and a reduced life expectancy. Although Fabry disease is an X-linked disorder, both genders may be affected, but generally to a lesser extent in females. The disease spectrum ranges from classic early-onset disease to...
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Full-text available
Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in...
Article
Background Human experimental pain models in healthy subjects offer unique possibilities to study mechanisms of pain within a defined setting of expected pain symptoms, signs and mechanisms. Previous trials in healthy subjects demonstrated that topical application of 40% menthol is suitable to induce cold hyperalgesia. The objective of this study w...
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Referred and projecting pain can be observed in acute and chronic pain states. We present the case of a 69-year-old female patient with postherpetic neuralgia (PHN) in dermatome Th2/3 who reported that touching the ipsilateral earlap (dermatome C2) would enhance pain and dynamic mechanical allodynia (DMA) in the affected Th2/3-dermatome. The aim wa...
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Background Low back pain is major health care problem causing tremendous economic cots. Methods Clinical manifestation of low back pain (LBP) was characterized in 35,446 patients. We focused on the comparison of the acute, subacute, and chronic LBP stage with regard to patients’ age, based on epidemiological and clinical questionnaires (e.g. painD...
Article
Objective: Successful treatment of chronic low back pain (LBP) is difficult in clinical practice and hard to measure in trials. One reason might be the use of insufficient outcome parameters. The aim was to investigate the importance of typical clinical characteristics of chronic LBP on QoL and functionality. Methods: A total of 51 patients with ch...
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Background Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease...
Article
Neuropathic pain-pain caused by a lesion or disease of the somatosensory nervous system-is underdiagnosed and difficult to treat. However, development of easy-to-use questionnaires based mainly on self-reports of symptoms has improved diagnosis and management. Two types of questionnaires (screening and assessment) have been validated, and rapidly t...
Article
Chronic injury of limb nerves leading to neuropathic pain affects deep somatic nerves. Here the functional properties of injured afferent fibers in the lateral gastrocnemius-soleus nerve were investigated 20 days and 80 days after suturing the central stump of this muscle nerve to the distal stump of the sural nerve in anesthetized rats. Neurophysi...
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Introduction Animal experimental evidence suggests that mechanisms of pain generation and response to treatment differ between neuropathic pain in the cephalic and the extracephalic innervation territories. Objectives The objective of the study was to examine whether in humans an identical peripheral painful neuropathy is associated with different...
Article
As an indirect approach to relate previously identified sensory phenotypes of patients suffering from peripheral neuropathic pain to underlying mechanisms, we used a published sorting algorithm to estimate the prevalence of denervation, peripheral and central sensitization in 657 healthy subjects undergoing experimental models of nerve block (compr...
Chapter
Schmerzen sind im Akutstadium eine protektive Reaktion des Körpers, um sich vor potenziellen Gewebeschädigungen zu schützen. An dieser protektiven Reaktion sind sowohl sensorische Afferenzen als auch somatische und vegetative motorische Efferenzen beteiligt. Daneben spielen assoziierte kognitive, affektive und endokrine Komponenten eine Rolle. Akut...
Article
Full-text available
Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin‐induced acute neuropathy with (n = 6) and without (n = 7) cold hyperalgesia were tested by applying a pre...
Article
Objectives: Hyperalgesia and allodynia are typical signs of neuropathic pain. Quantitative sensory testing (QST) is a validated tool to clinically assess these phenomena. However, whether QST reveals findings that are reported by the patients is unclear. The aim of this study was therefore to investigate the association between self-reported sympt...
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Patients with the same neuropathic pain disorder may have completely different sensory signs and symptoms yet receive the same medicinal treatment. New concepts suggest that patient stratification according to their pain mechanisms, reflected in their sensory phenotype, could be promising to implement an individualized therapy in neuropathic pain....
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Background C-fibers express transient receptor potential (TRP) channels. These high-voltage gated channels function as integrators of different physical stresses (e.g. heat, protons, ATP). Additionally channel activation can be induced by capsaicin. Topically applied, capsaicin elicits burning pain, heat and mechanical hyperalgesia and serves as a...
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In a recent cluster analysis, it has been shown that patients with peripheral neuropathic pain can be grouped into 3 sensory phenotypes based on quantitative sensory testing profiles, which are mainly characterized by either sensory loss, intact sensory function and mild thermal hyperalgesia and/or allodynia, or loss of thermal detection and mild m...