Gunnar Wasner - Profile on Academia.edu (original) (raw)
Papers by Gunnar Wasner
PLOS ONE, 2017
Background C-fibers express transient receptor potential (TRP) channels. These high-voltage gated... more 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 human surrogate model for pain. It was suggested that the TRPV1-variant rs8065080 (1911A>G) plays a pivotal role in patients with neuropathic pain syndromes. We investigated the effect of this TRPV1-SNP on thermal sensitivity and superficial skin perfusion in 25 healthy subjects. Methods and findings Nine subjects being homozygous TRPV1 wild type (AA), 8 heterozygous (AG) and 8 homozygous variant (GG) carriers were selected out of a pool of genotyped healthy individuals. Under physiological conditions (no capsaicin application), there was no statistical significant difference in thermal thresholds or skin perfusion between carriers of different TRPV1 1199A>G genotypes. However, intra-individual calculations (Δ% pre vs. post capsaicin) revealed (1) less warm-detection in AA/AG (-82.1%) compared to GG (-13.1%) and (2) a gain of heat pain sensitivity in AA/AG (+22.2%) compared to GG carriers (+15.6%) after adjustment for perfusion measurements ((1)p = 0.009, (2)p = 0.021). Conclusion Presence of homozygous variant TRPV1 genotype (GG) demonstrated less capsaicininduced warm hypoesthesia in warm-detection and less capsaicin-induced heat pain sensitivity suggesting an altered channel function. This demonstrates not only the functional influence of TRPV1 rs8065080 polymorphism itself; it further more underpins the relevance of
Somatotopic mismatch following stroke: a pathophysiological condition escaping detection
Case Reports, 2012
Clinical evaluation of somatosensory deficits in stroke patients is very limited and usually does... more Clinical evaluation of somatosensory deficits in stroke patients is very limited and usually does not include testing of somatotopic organisation, which is a prerequisite for meaningful interpretation of sensory input and sensorimotor control. Detailed tactile testing of the left hand of a 54-year-old patient suffering from sensory deficit and central pain after a right-sided stroke revealed severe distortion of somatotopic sensory maps as evidenced by incorrect localisation of the point stimuli. Unlike previously reported gross somatotopic remapping taking place within reduced representational space after lesion, this is the first case report revealing chaotic scrambled somatosensory maps. While the incidence of such scrambled somatotopic representation of tactile input is not yet known in stroke patients, current observations indicate that in-depth investigations of somatotopic organisation of affected area may reveal the underlying cause for various functional deficits including central pain. Thus, new rehabilitation strategies may need to be developed specifically for such patients.
9 Herzfrequenzvariabilität
Die physiologische Variation der Herzfrequenz wird durch die autonome Innervation des Herzens ver... more Die physiologische Variation der Herzfrequenz wird durch die autonome Innervation des Herzens vermittelt. Eine quantitative Analyse dieser Variation gibt Aufschluss über die Funktion dieser Innervation. 19.1 Anatomie und Physiologie 19.1.1 Autonome Innervation des Herzens Sowohl postganglionäre adrenerge sympathische als auch cholinerge parasympathische Neuronen innervieren das Herz und beeinflussen die Chronotropie, Inotropie und Dromotropie. Der hemmende parasympathische Einfluss auf diese Herzfunktionen überwiegt im Liegen unter Ruhe-bedingungen, sympathische Regulationen sind minimal. 19.1.2 Herzfrequenzvariabilität während normaler Aktivität Physiologisch variiert während normaler täglicher Aktivi-täten der zeitliche Abstand zwischen den Herzschlägen ständig. Die intrinsische autonome Frequenz des kardialen Schrittmachers wird durch die negativ-chronotrope Wir-kung der parasympathischen und die positiv-chronotrope Wirkung der sympathischen Innervation sowie durch hu-morale Mech...
[The symptom sympathetic maintained pain]
Der Schmerz
Sympathetically maintained pain is a symptom which occurs in neuropathic pain syndromes of differ... more Sympathetically maintained pain is a symptom which occurs in neuropathic pain syndromes of different etiologies. From animal experiments it is known that nociceptive afferents after partial nerve lesions develop adrenergic sensitivity at the site of the injury. In addition, a sympathetic-afferent coupling takes place in the dorsal root ganglia. It is still controversial if these pathophysiological mechanisms are responsible for the developing of SMP in humans. Clinical studies support the idea that also in humans the application of adrenergic substances in pharmacological doses is capable to influence nociception, but a direct interaction between the sympathetic system and the nociceptive system had not been demonstrated so far. By using a thermal suit for whole body cooling and warming, which produces low and high activity of sympathetic vasoconstrictor neurons, it was possible for the first time to demonstrate an interaction between physiological changes in sympathetic activity an...
Chapter 50 Pain in Parkinson’s disease
Handbook of Clinical Neurology
[Recent trends in understanding and therapy of complex regional pain syndromes]
Der Anaesthesist, 2003
Since the term "complex regional pain syndromes" (CRPS) was introduced based on a revis... more Since the term "complex regional pain syndromes" (CRPS) was introduced based on a revised taxonomy for disorders previously called reflex sympathetic dystrophy and causalgia in 1995, much knowledge grew up on the understanding and therapy of the disease. This review gives an overview on the clinical characteristics, pathophysiology, diagnostic tools and therapeutic options in CRPS. It will especially focus on recent findings on the role of the sympathetic nervous system, the central nervous system and peripheral inflammatory processes as underlying mechanisms. Although there is no diagnostic gold standard, careful clinical evaluation and additional apparative test procedures are very helpful for the diagnosis. An early and interdisciplinary approach is the basis for an optimal and successful treatment.
Pain, 1999
Recently, Cervero and Laird (NeuroReport, 7 (1996) 526-528; Pain, 68 (1996) 13-23) proposed a new... more Recently, Cervero and Laird (NeuroReport, 7 (1996) 526-528; Pain, 68 (1996) 13-23) proposed a new pathophysiological mechanism of dynamic mechanical allodynia in skin. Using the capsaicin pain model in humans, they showed that light mechanical stimulation within an area of secondary mechanical allodynia induces vasodilatation measured by laser-Doppler flowmetry. They suggested that the low-threshold A beta-mechanoreceptive fibres depolarize the central terminals of nociceptive primary afferent neurons via interneurons. Consequently, the vasodilatation is produced by impulses conducted antidromically in nociceptive C-axons. The allodynia was proposed to result from depolarization of central terminals of primary afferent neurons with C-fibres with activation of nociceptive dorsal horn neurons. In order to extend these findings, we used the same experimental approach but additionally stimulated the A beta-fibres electrically to evoke secondary allodynia during simultaneous monitoring s...
A case of pain, motor impairment, and swelling of the arm after acute herpes zoster infection
Pain, 2012
Complex regional pain syndrome (CRPS) and postherpetic neuralgia (PHN) represent neuropathic pain... more Complex regional pain syndrome (CRPS) and postherpetic neuralgia (PHN) represent neuropathic pain syndromes that may appear with similar clinical signs and symptoms. Medical history and clinical distribution of symptoms and signs (PHN typically at the thorax; CRPS typically at the limbs) is obvious in most cases, helping to discriminate between both disorders. Here, we present a patient suffering from CRPS II following PHN of one upper extremity. This case demonstrates that both etiology and part of the body affected by a neuropathy influence the pain phenotype.
[Quantitative thermotest - investigations of thermal and nociceptive afferents in neuropathy. Is a multicentric approach useful to investigate rare painful neuropathies?]
Schmerz (Berlin, Germany), Jan 10, 1998
Disturbances of small afferent nerve fibres play an important role in painful neuropathies. Quant... more Disturbances of small afferent nerve fibres play an important role in painful neuropathies. Quantitative thermotest offers a possibility to quantify these disturbances that can not be detected by conventional electrophysiology. It is a psychophysical method to investigate thermal and nociceptive afferents by determining thermal thresholds. Former experiences have shown that quantitative thermotest can be a helpful tool not only in daily routine but also for research work concerning pathophysiological mechanisms of neuropathy. Therefore a multicentric approach to investigate rare painful neuropathies seems to be useful.
[Sympathetic nervous system and pain--some open questions]
Schmerz (Berlin, Germany), Jan 27, 1998
Neuropathic pain syndromes may be treated by intervention at the sympathetic nervous system. The ... more Neuropathic pain syndromes may be treated by intervention at the sympathetic nervous system. The pain in these syndromes is therefore called sympathetically maintained pain (SMP). Typical disorders with a SMP component are complex regional pain syndromes (reflex sympathetic dystrophy and causalgia), traumatic neuralgias and herpes zoster. Open questions are how the efferent sympathetic nervous system is capable of influencing pain sensation and which mechanisms underly the autonomic dysregulation often observed in these syndromes.(1) Somatic afferents that project through the sympathetic trunk do not exist. Therefore, a pure sympathetic block does not block afferent information arising from the affected extremity. What alternatives are possible? Under pathophysiological conditions a functional interaction of efferent sympathetic fibers and afferent nociceptive fibers could be demonstrated in patients and animal studies. The intensity of this coupling varies considerably between indi...
Docetaxel-induced nail changes--a neurogenic mechanism: a case report
Journal of neuro-oncology, 2002
Docetaxel is a new taxoid widely used in chemotherapy for advanced breast cancer and other solid ... more Docetaxel is a new taxoid widely used in chemotherapy for advanced breast cancer and other solid malignancies. Painful nail changes with onycholysis occur in about 40% of docetaxel-treated patients as a prominent adverse effect. We report a patient with a complete peripheral palsy of the right arm due to advanced breast cancer with diffuse tumor infiltration of the brachial plexus. Treatment with docetaxel led to onycholysis at all extremities except the paretic hand. Sensory and motoric innervation measured by nerve conduction studies showed a complete loss of large nerve fiber function of the right arm. Function of deep mechanosensitive A beta-fibers (quantitative vibrametry) was severely decreased, but not absent. Sympathetic reflexes (induced by deep inspiration and measured with laser Doppler flowmetry) were absent on the right side and skin temperature was decreased consistent with a complete sympathetic denervation. Small afferent fibers investigated by quantitative thermotes...
Pain, 2008
Despite the development of the IASP criteria, diagnosing complex regional pain syndrome (CRPS) re... more Despite the development of the IASP criteria, diagnosing complex regional pain syndrome (CRPS) remains a challenge because all symptoms vary interindividually, including the vascular abnormalities. Previous studies showed that skin temperature asymmetries between the affected and contralateral extremity around 2°C are useful for diagnosing CRPS. However, they were either assessed only at one single point in time or during specific investigations including controlled thermoregulatory modulation of sympathetic activity which limits their practicability. The present study evaluated long-term skin temperature changes under everyday circumstances in 22 patients with CRPS, 18 patients with limb pain of other origin and 23 healthy controls. The asymmetries in skin temperature and oscillation number (Q Oscill ), the percentage of assessed time with a-synchron temperature changes on both body sides and the determination coefficient of the individual regression (r 2 id ) were compared between the groups. Patients with CRPS differed significantly from healthy controls in nearly all parameters. Minor differences between both patient groups were found regarding the percentage of assessed time with side difference >2°C (DT2). However, both patient groups differed significantly in parameters characterizing the skin temperature dynamics. A sum score (2ÃQ Oscill + r 2 id + DT2) allowed diagnosing CRPS with a specificity of 67% vs. patients with other painful diseases and 79% vs. healthy controls (sensitivity: 73%, respectively, 94%) and reflected the severity of the dysfunction in CRPS better than the mean skin temperature side differences alone. The applied skin temperature analysis can be easily applied in the clinical settings and serves as a further facet in the difficult diagnosis of CRPS. Ó
Traumatic neuralgias: complex regional pain syndromes (reflex sympathetic dystrophy and causalgia): clinical characteristics, pathophysiological mechanisms and therapy
Neurologic clinics, 1998
Complex regional pain syndromes (CPRS) may develop as a disproportionate consequence of a trauma ... more Complex regional pain syndromes (CPRS) may develop as a disproportionate consequence of a trauma affecting the limbs without (CRPS I, reflex sympathetic dystrophy) or with (CRPS II, causalgia) obvious nerve lesions. The clinical picture of CRPS consists of asymmetrical distal extremity pain, swelling, and autonomic (sympathetic) and motor symptoms. Changes in the peripheral and central somatosensory, autonomic and motor processing, and a pathologic interaction of sympathetic and afferent systems are discussed as underlying pathophysiologic mechanisms. Therapeutic strategies include pharmacologic pain relief, sympatholytic interventions, and rehabilitation.
Postherpetic Neuralgia: Basic Research and Clinical Implications
Reviews in Analgesia, 2007
Nature Reviews Neurology, 2012
| Pain is a nonmotor symptom that substantially affects the quality of life of at least one-third... more | Pain is a nonmotor symptom that substantially affects the quality of life of at least one-third of patients with Parkinson disease (PD). Interestingly, patients with PD frequently report different types of pain, and a successful approach to distinguish between these pains is required so that effective treatment strategies can be established. Differences between these pains are attributable to varying peripheral pain mechanisms, the role of motor symptoms in causing or amplifying pain, and the role of PD pathophysiology in pain processing. In this Review, we propose a four-tier taxonomy to improve classification of pain in PD. This taxonomy assigns nociceptive, neuropathic and miscellaneous pains to distinct categories, as well as further characterization into subcategories. Currently, treatment of pain in PD is based on empirical data only, owing to a lack of controlled studies. The facultative symptom of 'dopaminergically maintained pain' refers to pain that benefits from antiparkinson medication. Here, we also present additional pharmacological and nonpharmacological treatment approaches, which can be targeted to a specific pain following classification using our taxonomy.
Pain: Clinical pain assessment: from bedside to better treatment
Nature Reviews Neurology, 2009
Peripheral burning cold pain
Pain, 2006
Local anaesthetic sympathetic blockade for complex regional pain syndrome
Reviews, 1996
This is an update of the original Cochrane review published in The Cochrane Library, 2005, Issue ... more This is an update of the original Cochrane review published in The Cochrane Library, 2005, Issue 4, on local anaesthetic blockade (LASB) of the sympathetic chain used to treat complex regional pain syndrome (CRPS). To assess the efficacy of LASB for the treatment of pain in CRPS and to evaluate the incidence of adverse effects of the procedure. We updated searches of the Cochrane Pain, Palliative and Supportive Care Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library (Issue 11 of 12, 2012), MEDLINE (1966 to 22/11/12), EMBASE (1974 to 22/11/12), LILACS (1982 to 22/11/12), conference abstracts of the World Congresses of the International Association for the Study of Pain (1995 to 2010), and various clinical trial registers (inception to 2012). We also searched bibliographies from retrieved articles for additional studies. We considered for inclusion randomised controlled trials (RCTs) that evaluated the effect of sympathetic blockade with local anaesthetics in children or adults with CRPS. The outcomes of interest were reduction in pain intensity levels, the proportion who achieved moderate or substantial pain relief, the duration of pain relief, and the presence of adverse effects in each treatment arm. We included an additional 10 studies (combined n = 363) in this update. Overall we include 12 studies (combined n = 386). All included studies were assessed to be at high or unclear risk of bias.Three small studies compared LASB to placebo/sham. We were able to pool the results from two of these trials (intervention n = 23). Pooling did not demonstrate significant short-term benefit for LASB (in terms of the risk of a 50% reduction of pain scores).Of two studies that investigated LASB as an addition to rehabilitation treatment, the only study that reported pain outcomes demonstrated no additional benefit from LASB.Eight small randomised studies compared sympathetic blockade to another active intervention. Most studies found no difference in pain outcomes between sympathetic block and other active treatments.Only five studies reported adverse effects, all with minor effects reported. This update has found similar results to the original systematic review. There remains a scarcity of published evidence to support the use of local anaesthetic sympathetic blockade for CRPS. From the existing evidence it is not possible to draw firm conclusions regarding the efficacy or safety of this intervention but the limited data available do not suggest that LASB is effective for reducing pain in CRPS.
Spinal Cord, 2003
Complex regional pain syndromes (CRPS, formerly re¯ex sympathetic dystrophy and causalgia) are ne... more Complex regional pain syndromes (CRPS, formerly re¯ex sympathetic dystrophy and causalgia) are neuropathic pain conditions of one extremity developing inadequately after a trauma. The initiating trauma aects primarily the extremity, but can also be a central lesion (e.g., spinal cord injury, stroke). CRPS is clinically characterized by sensory, autonomic and motor disturbances. Pathophysiologically there is evidence for functional changes within the central nervous system and for involvement of peripheral in¯ammatory processes. The sympathetic nervous system plays a key role in maintaining pain and autonomic dysfunction in the aected extremity. After a primary central lesion, secondary peripheral changes in the paretic extremity are suggested to be important in initiating a CRPS. Though there is no diagnostic gold standard, careful clinical evaluation and additional test procedures should lead to an adequate diagnosis. An early diagnosis and an interdisciplinary approach are important for optimal and successful treatment.
PLoS ONE, 2011
Transient receptor potential channels are important mediators of thermal and mechanical stimuli a... more Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G.A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p = 0.03), and transient receptor potential vanilloid 1 1911A.G (rs8065080, I585V) with cold hypoalgesia (p = 0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A.G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p,0.001) and transient receptor potential vanilloid 1 1103C.G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.
PLOS ONE, 2017
Background C-fibers express transient receptor potential (TRP) channels. These high-voltage gated... more 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 human surrogate model for pain. It was suggested that the TRPV1-variant rs8065080 (1911A>G) plays a pivotal role in patients with neuropathic pain syndromes. We investigated the effect of this TRPV1-SNP on thermal sensitivity and superficial skin perfusion in 25 healthy subjects. Methods and findings Nine subjects being homozygous TRPV1 wild type (AA), 8 heterozygous (AG) and 8 homozygous variant (GG) carriers were selected out of a pool of genotyped healthy individuals. Under physiological conditions (no capsaicin application), there was no statistical significant difference in thermal thresholds or skin perfusion between carriers of different TRPV1 1199A>G genotypes. However, intra-individual calculations (Δ% pre vs. post capsaicin) revealed (1) less warm-detection in AA/AG (-82.1%) compared to GG (-13.1%) and (2) a gain of heat pain sensitivity in AA/AG (+22.2%) compared to GG carriers (+15.6%) after adjustment for perfusion measurements ((1)p = 0.009, (2)p = 0.021). Conclusion Presence of homozygous variant TRPV1 genotype (GG) demonstrated less capsaicininduced warm hypoesthesia in warm-detection and less capsaicin-induced heat pain sensitivity suggesting an altered channel function. This demonstrates not only the functional influence of TRPV1 rs8065080 polymorphism itself; it further more underpins the relevance of
Somatotopic mismatch following stroke: a pathophysiological condition escaping detection
Case Reports, 2012
Clinical evaluation of somatosensory deficits in stroke patients is very limited and usually does... more Clinical evaluation of somatosensory deficits in stroke patients is very limited and usually does not include testing of somatotopic organisation, which is a prerequisite for meaningful interpretation of sensory input and sensorimotor control. Detailed tactile testing of the left hand of a 54-year-old patient suffering from sensory deficit and central pain after a right-sided stroke revealed severe distortion of somatotopic sensory maps as evidenced by incorrect localisation of the point stimuli. Unlike previously reported gross somatotopic remapping taking place within reduced representational space after lesion, this is the first case report revealing chaotic scrambled somatosensory maps. While the incidence of such scrambled somatotopic representation of tactile input is not yet known in stroke patients, current observations indicate that in-depth investigations of somatotopic organisation of affected area may reveal the underlying cause for various functional deficits including central pain. Thus, new rehabilitation strategies may need to be developed specifically for such patients.
9 Herzfrequenzvariabilität
Die physiologische Variation der Herzfrequenz wird durch die autonome Innervation des Herzens ver... more Die physiologische Variation der Herzfrequenz wird durch die autonome Innervation des Herzens vermittelt. Eine quantitative Analyse dieser Variation gibt Aufschluss über die Funktion dieser Innervation. 19.1 Anatomie und Physiologie 19.1.1 Autonome Innervation des Herzens Sowohl postganglionäre adrenerge sympathische als auch cholinerge parasympathische Neuronen innervieren das Herz und beeinflussen die Chronotropie, Inotropie und Dromotropie. Der hemmende parasympathische Einfluss auf diese Herzfunktionen überwiegt im Liegen unter Ruhe-bedingungen, sympathische Regulationen sind minimal. 19.1.2 Herzfrequenzvariabilität während normaler Aktivität Physiologisch variiert während normaler täglicher Aktivi-täten der zeitliche Abstand zwischen den Herzschlägen ständig. Die intrinsische autonome Frequenz des kardialen Schrittmachers wird durch die negativ-chronotrope Wir-kung der parasympathischen und die positiv-chronotrope Wirkung der sympathischen Innervation sowie durch hu-morale Mech...
[The symptom sympathetic maintained pain]
Der Schmerz
Sympathetically maintained pain is a symptom which occurs in neuropathic pain syndromes of differ... more Sympathetically maintained pain is a symptom which occurs in neuropathic pain syndromes of different etiologies. From animal experiments it is known that nociceptive afferents after partial nerve lesions develop adrenergic sensitivity at the site of the injury. In addition, a sympathetic-afferent coupling takes place in the dorsal root ganglia. It is still controversial if these pathophysiological mechanisms are responsible for the developing of SMP in humans. Clinical studies support the idea that also in humans the application of adrenergic substances in pharmacological doses is capable to influence nociception, but a direct interaction between the sympathetic system and the nociceptive system had not been demonstrated so far. By using a thermal suit for whole body cooling and warming, which produces low and high activity of sympathetic vasoconstrictor neurons, it was possible for the first time to demonstrate an interaction between physiological changes in sympathetic activity an...
Chapter 50 Pain in Parkinson’s disease
Handbook of Clinical Neurology
[Recent trends in understanding and therapy of complex regional pain syndromes]
Der Anaesthesist, 2003
Since the term "complex regional pain syndromes" (CRPS) was introduced based on a revis... more Since the term "complex regional pain syndromes" (CRPS) was introduced based on a revised taxonomy for disorders previously called reflex sympathetic dystrophy and causalgia in 1995, much knowledge grew up on the understanding and therapy of the disease. This review gives an overview on the clinical characteristics, pathophysiology, diagnostic tools and therapeutic options in CRPS. It will especially focus on recent findings on the role of the sympathetic nervous system, the central nervous system and peripheral inflammatory processes as underlying mechanisms. Although there is no diagnostic gold standard, careful clinical evaluation and additional apparative test procedures are very helpful for the diagnosis. An early and interdisciplinary approach is the basis for an optimal and successful treatment.
Pain, 1999
Recently, Cervero and Laird (NeuroReport, 7 (1996) 526-528; Pain, 68 (1996) 13-23) proposed a new... more Recently, Cervero and Laird (NeuroReport, 7 (1996) 526-528; Pain, 68 (1996) 13-23) proposed a new pathophysiological mechanism of dynamic mechanical allodynia in skin. Using the capsaicin pain model in humans, they showed that light mechanical stimulation within an area of secondary mechanical allodynia induces vasodilatation measured by laser-Doppler flowmetry. They suggested that the low-threshold A beta-mechanoreceptive fibres depolarize the central terminals of nociceptive primary afferent neurons via interneurons. Consequently, the vasodilatation is produced by impulses conducted antidromically in nociceptive C-axons. The allodynia was proposed to result from depolarization of central terminals of primary afferent neurons with C-fibres with activation of nociceptive dorsal horn neurons. In order to extend these findings, we used the same experimental approach but additionally stimulated the A beta-fibres electrically to evoke secondary allodynia during simultaneous monitoring s...
A case of pain, motor impairment, and swelling of the arm after acute herpes zoster infection
Pain, 2012
Complex regional pain syndrome (CRPS) and postherpetic neuralgia (PHN) represent neuropathic pain... more Complex regional pain syndrome (CRPS) and postherpetic neuralgia (PHN) represent neuropathic pain syndromes that may appear with similar clinical signs and symptoms. Medical history and clinical distribution of symptoms and signs (PHN typically at the thorax; CRPS typically at the limbs) is obvious in most cases, helping to discriminate between both disorders. Here, we present a patient suffering from CRPS II following PHN of one upper extremity. This case demonstrates that both etiology and part of the body affected by a neuropathy influence the pain phenotype.
[Quantitative thermotest - investigations of thermal and nociceptive afferents in neuropathy. Is a multicentric approach useful to investigate rare painful neuropathies?]
Schmerz (Berlin, Germany), Jan 10, 1998
Disturbances of small afferent nerve fibres play an important role in painful neuropathies. Quant... more Disturbances of small afferent nerve fibres play an important role in painful neuropathies. Quantitative thermotest offers a possibility to quantify these disturbances that can not be detected by conventional electrophysiology. It is a psychophysical method to investigate thermal and nociceptive afferents by determining thermal thresholds. Former experiences have shown that quantitative thermotest can be a helpful tool not only in daily routine but also for research work concerning pathophysiological mechanisms of neuropathy. Therefore a multicentric approach to investigate rare painful neuropathies seems to be useful.
[Sympathetic nervous system and pain--some open questions]
Schmerz (Berlin, Germany), Jan 27, 1998
Neuropathic pain syndromes may be treated by intervention at the sympathetic nervous system. The ... more Neuropathic pain syndromes may be treated by intervention at the sympathetic nervous system. The pain in these syndromes is therefore called sympathetically maintained pain (SMP). Typical disorders with a SMP component are complex regional pain syndromes (reflex sympathetic dystrophy and causalgia), traumatic neuralgias and herpes zoster. Open questions are how the efferent sympathetic nervous system is capable of influencing pain sensation and which mechanisms underly the autonomic dysregulation often observed in these syndromes.(1) Somatic afferents that project through the sympathetic trunk do not exist. Therefore, a pure sympathetic block does not block afferent information arising from the affected extremity. What alternatives are possible? Under pathophysiological conditions a functional interaction of efferent sympathetic fibers and afferent nociceptive fibers could be demonstrated in patients and animal studies. The intensity of this coupling varies considerably between indi...
Docetaxel-induced nail changes--a neurogenic mechanism: a case report
Journal of neuro-oncology, 2002
Docetaxel is a new taxoid widely used in chemotherapy for advanced breast cancer and other solid ... more Docetaxel is a new taxoid widely used in chemotherapy for advanced breast cancer and other solid malignancies. Painful nail changes with onycholysis occur in about 40% of docetaxel-treated patients as a prominent adverse effect. We report a patient with a complete peripheral palsy of the right arm due to advanced breast cancer with diffuse tumor infiltration of the brachial plexus. Treatment with docetaxel led to onycholysis at all extremities except the paretic hand. Sensory and motoric innervation measured by nerve conduction studies showed a complete loss of large nerve fiber function of the right arm. Function of deep mechanosensitive A beta-fibers (quantitative vibrametry) was severely decreased, but not absent. Sympathetic reflexes (induced by deep inspiration and measured with laser Doppler flowmetry) were absent on the right side and skin temperature was decreased consistent with a complete sympathetic denervation. Small afferent fibers investigated by quantitative thermotes...
Pain, 2008
Despite the development of the IASP criteria, diagnosing complex regional pain syndrome (CRPS) re... more Despite the development of the IASP criteria, diagnosing complex regional pain syndrome (CRPS) remains a challenge because all symptoms vary interindividually, including the vascular abnormalities. Previous studies showed that skin temperature asymmetries between the affected and contralateral extremity around 2°C are useful for diagnosing CRPS. However, they were either assessed only at one single point in time or during specific investigations including controlled thermoregulatory modulation of sympathetic activity which limits their practicability. The present study evaluated long-term skin temperature changes under everyday circumstances in 22 patients with CRPS, 18 patients with limb pain of other origin and 23 healthy controls. The asymmetries in skin temperature and oscillation number (Q Oscill ), the percentage of assessed time with a-synchron temperature changes on both body sides and the determination coefficient of the individual regression (r 2 id ) were compared between the groups. Patients with CRPS differed significantly from healthy controls in nearly all parameters. Minor differences between both patient groups were found regarding the percentage of assessed time with side difference >2°C (DT2). However, both patient groups differed significantly in parameters characterizing the skin temperature dynamics. A sum score (2ÃQ Oscill + r 2 id + DT2) allowed diagnosing CRPS with a specificity of 67% vs. patients with other painful diseases and 79% vs. healthy controls (sensitivity: 73%, respectively, 94%) and reflected the severity of the dysfunction in CRPS better than the mean skin temperature side differences alone. The applied skin temperature analysis can be easily applied in the clinical settings and serves as a further facet in the difficult diagnosis of CRPS. Ó
Traumatic neuralgias: complex regional pain syndromes (reflex sympathetic dystrophy and causalgia): clinical characteristics, pathophysiological mechanisms and therapy
Neurologic clinics, 1998
Complex regional pain syndromes (CPRS) may develop as a disproportionate consequence of a trauma ... more Complex regional pain syndromes (CPRS) may develop as a disproportionate consequence of a trauma affecting the limbs without (CRPS I, reflex sympathetic dystrophy) or with (CRPS II, causalgia) obvious nerve lesions. The clinical picture of CRPS consists of asymmetrical distal extremity pain, swelling, and autonomic (sympathetic) and motor symptoms. Changes in the peripheral and central somatosensory, autonomic and motor processing, and a pathologic interaction of sympathetic and afferent systems are discussed as underlying pathophysiologic mechanisms. Therapeutic strategies include pharmacologic pain relief, sympatholytic interventions, and rehabilitation.
Postherpetic Neuralgia: Basic Research and Clinical Implications
Reviews in Analgesia, 2007
Nature Reviews Neurology, 2012
| Pain is a nonmotor symptom that substantially affects the quality of life of at least one-third... more | Pain is a nonmotor symptom that substantially affects the quality of life of at least one-third of patients with Parkinson disease (PD). Interestingly, patients with PD frequently report different types of pain, and a successful approach to distinguish between these pains is required so that effective treatment strategies can be established. Differences between these pains are attributable to varying peripheral pain mechanisms, the role of motor symptoms in causing or amplifying pain, and the role of PD pathophysiology in pain processing. In this Review, we propose a four-tier taxonomy to improve classification of pain in PD. This taxonomy assigns nociceptive, neuropathic and miscellaneous pains to distinct categories, as well as further characterization into subcategories. Currently, treatment of pain in PD is based on empirical data only, owing to a lack of controlled studies. The facultative symptom of 'dopaminergically maintained pain' refers to pain that benefits from antiparkinson medication. Here, we also present additional pharmacological and nonpharmacological treatment approaches, which can be targeted to a specific pain following classification using our taxonomy.
Pain: Clinical pain assessment: from bedside to better treatment
Nature Reviews Neurology, 2009
Peripheral burning cold pain
Pain, 2006
Local anaesthetic sympathetic blockade for complex regional pain syndrome
Reviews, 1996
This is an update of the original Cochrane review published in The Cochrane Library, 2005, Issue ... more This is an update of the original Cochrane review published in The Cochrane Library, 2005, Issue 4, on local anaesthetic blockade (LASB) of the sympathetic chain used to treat complex regional pain syndrome (CRPS). To assess the efficacy of LASB for the treatment of pain in CRPS and to evaluate the incidence of adverse effects of the procedure. We updated searches of the Cochrane Pain, Palliative and Supportive Care Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library (Issue 11 of 12, 2012), MEDLINE (1966 to 22/11/12), EMBASE (1974 to 22/11/12), LILACS (1982 to 22/11/12), conference abstracts of the World Congresses of the International Association for the Study of Pain (1995 to 2010), and various clinical trial registers (inception to 2012). We also searched bibliographies from retrieved articles for additional studies. We considered for inclusion randomised controlled trials (RCTs) that evaluated the effect of sympathetic blockade with local anaesthetics in children or adults with CRPS. The outcomes of interest were reduction in pain intensity levels, the proportion who achieved moderate or substantial pain relief, the duration of pain relief, and the presence of adverse effects in each treatment arm. We included an additional 10 studies (combined n = 363) in this update. Overall we include 12 studies (combined n = 386). All included studies were assessed to be at high or unclear risk of bias.Three small studies compared LASB to placebo/sham. We were able to pool the results from two of these trials (intervention n = 23). Pooling did not demonstrate significant short-term benefit for LASB (in terms of the risk of a 50% reduction of pain scores).Of two studies that investigated LASB as an addition to rehabilitation treatment, the only study that reported pain outcomes demonstrated no additional benefit from LASB.Eight small randomised studies compared sympathetic blockade to another active intervention. Most studies found no difference in pain outcomes between sympathetic block and other active treatments.Only five studies reported adverse effects, all with minor effects reported. This update has found similar results to the original systematic review. There remains a scarcity of published evidence to support the use of local anaesthetic sympathetic blockade for CRPS. From the existing evidence it is not possible to draw firm conclusions regarding the efficacy or safety of this intervention but the limited data available do not suggest that LASB is effective for reducing pain in CRPS.
Spinal Cord, 2003
Complex regional pain syndromes (CRPS, formerly re¯ex sympathetic dystrophy and causalgia) are ne... more Complex regional pain syndromes (CRPS, formerly re¯ex sympathetic dystrophy and causalgia) are neuropathic pain conditions of one extremity developing inadequately after a trauma. The initiating trauma aects primarily the extremity, but can also be a central lesion (e.g., spinal cord injury, stroke). CRPS is clinically characterized by sensory, autonomic and motor disturbances. Pathophysiologically there is evidence for functional changes within the central nervous system and for involvement of peripheral in¯ammatory processes. The sympathetic nervous system plays a key role in maintaining pain and autonomic dysfunction in the aected extremity. After a primary central lesion, secondary peripheral changes in the paretic extremity are suggested to be important in initiating a CRPS. Though there is no diagnostic gold standard, careful clinical evaluation and additional test procedures should lead to an adequate diagnosis. An early diagnosis and an interdisciplinary approach are important for optimal and successful treatment.
PLoS ONE, 2011
Transient receptor potential channels are important mediators of thermal and mechanical stimuli a... more Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G.A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p = 0.03), and transient receptor potential vanilloid 1 1911A.G (rs8065080, I585V) with cold hypoalgesia (p = 0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A.G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p,0.001) and transient receptor potential vanilloid 1 1103C.G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.