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Introduction
Skills and Expertise
Current institution
Additional affiliations
September 2010 - October 2010
Position
- Sensitization of spinal trigeminal neurons by environmental and internal factors
February 2009 - February 2009
August 2005 - December 2005
Education
October 1977 - April 1994
October 1974 - August 1981
Publications
Publications (201)
This article informs about important research results from recent years in the field of peripheral nociception. While pain is defined as a subjective phenomenon of perception, nociception comprises all peripheral and central neurophysiological mechanisms that can lead to pain. Nociception is initiated by nocisensors, which consist of afferent Aδ an...
Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been recognized as important mediators in migraine but their mechanisms of action and interaction have not been fully elucidated. Monoclonal anti-CGRP antibodies like fremanezumab are successful preventives of frequent migraine and can be used to study CGRP actions in preclinical exp...
Background
The role of calcitonin gene-related peptide (CGRP) in the cyclic pattern of cluster headache is unclear. To acquire biological insight and to comprehend why only episodic cluster headache responds to CGRP monoclonal antibodies, we examined whether plasma CGRP changes between disease states (i.e. bout, remission and chronic) and controls....
Background
Monoclonal antibodies directed against the neuropeptide calcitonin gene-related peptide (CGRP) are effective in the prevention of chronic and frequent episodic migraine. Since the antibodies do not cross the blood brain barrier, their antinociceptive effect is attributed to effects in meningeal tissues. We aimed to probe if such an antib...
Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic and frequent episodic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and aversive behaviour to noxious facial stimuli, which are characteristic pathophy...
Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and the aversive behaviour to noxious facial stimuli, which are characteristic pathophysiological changes...
Migraine pain is frequently accompanied by cranial hyperalgesia and allodynia. Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology but its role in facial hypersensitivity is not entirely clear. In this study, we investigated if the anti-CGRP monoclonal antibody fremanezumab, which is therapeutically used in chronic and...
Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved in the sex dimorphism of migraine attacks. In addition, the pituitary-derived hormone prolactin and...
Objective:
The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders.
Methods:
This is a narrative review of the literature regarding primary and secondary headache dis...
Background
Calcitonin gene related peptide (CGRP) plays a key role in the pathophysiology of migraine and is therefore considered a potential biomarker for primary headache disorders. The challenge remaining is establishing standardized protocols for its assessment in various extracellular compartments and identifying pathological situations associ...
Monoclonal antibodies directed against the neuropeptide calcitonin gene-related peptide (CGRP) belong to a new generation of therapeutics that are effective in the prevention of migraine. CGRP, a potent vasodilator, is strongly implicated in the pathophysiology of migraine, but its role remains to be fully elucidated. The hemisected rat head prepar...
Background
Migraine shows a cyclic pattern with an inter-ictal-, a pre-ictal, an ictal- and a post-ictal phase. We aimed to examine changes in psychophysical parameters during the migraine cycle.
Methods
The perception of nociceptive and non-nociceptive stimuli and an electrically induced axon-reflex-erythema were assessed in 20 healthy controls a...
Petasins are the pharmacologically active ingredients of butterbur and of therapeutic benefit in the treatment of migraine and tension headaches. Here, we summarize the pharmacology, safety and clinical efficacy of butterbur in the prevention of migraine attacks and present new data on its mode of action. We review published literature and study re...
The role of TRPA1 receptor channels in meningeal nociception underlying the generation of headaches is still unclear. Activating as well as inhibitory effects of TRPA1 agonists have been reported in animal models of headache. The aim of the present study was to clarify the effect of the TRPA1 agonist nitroxyl (HNO) delivered by Angeli’s salt in two...
Background
Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins...
Background
Calcitonin gene-related peptide (CGRP) is released from activated meningeal afferent fibres in the cranial dura mater, which likely accompanies severe headache attacks. Increased CGRP levels have been observed in different extracellular fluid compartments during primary headaches such as migraine but it is not entirely clear how CGRP is...
Clinical publications show consistently that headache is a common symptom in the coronavirus disease of 2019 (COVID-19). Several studies specifically investigated headache symptomatology and associated features in patients with COVID-19. The headache is frequently debilitating with manifold characters including migraine-like characteristics. Studie...
Background
Calcitonin gene-related peptide plasma levels have frequently been determined as a biomarker for primary headaches. However, published data is often inconsistent resulting from different methods that are not precisely described in most studies.
Methods
We applied a well-proven enzyme-linked immunosorbent assay to measure calcitonin gene...
The neuromodulator calcitonin gene-related peptide (CGRP) is known to facilitate nociceptive transmission in the superficial laminae of the spinal trigeminal nucleus caudalis (Sp5C). The central effects of CGRP in the Sp5C are very likely to contribute to the activation of central nociceptive pathways leading to attacks of severe headaches like mig...
The excellent craftsmanship of ancient Oriental and Central Asian textile dyers is already demonstrated in the remarkable brilliance and fastness of the colours of the so-called Pazyryk carpet, the by far oldest pile carpet found to date. This specimen resembles the advanced craftsmanship of Iron Age Central Asian textile production. We have employ...
Background
Changes in atmospheric pressure are suggested to trigger headaches. This pilot study was made to determine craniofacial sensations accompanying short phases of changing barometric pressure.
Methods
In a crossover design, 15 adult healthy subjects were exposed in a climate chamber to 8 min phases of barometric pressure lowering by 0, 20...
Background: Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins...
Background
The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses.
Methods
In isoflurane...
The mechanisms underlying headaches attributed to hypoxia are poorly known. The activation of spinal trigeminal neurons with meningeal afferent input is believed to be responsible for the generation of headaches. In the caudal spinal trigeminal nucleus of anaesthetized and ventilated rats, the spontaneous firing of neurons with input from the expos...
The trigeminal ganglion with its three trigeminal nerve tracts consists mainly of clusters of sensory neurons with their peripheral and central processes. Most neurons are surrounded by satellite glial cells and the axons are wrapped by myelinating and non-myelinating Schwann cells. Trigeminal neurons express various neuropeptides, most notably, ca...
The plasma of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated imm...
Calcitonin gene-related peptide (CGRP) is released from trigeminal afferents during migraine and cluster headache attacks and can be detected in the jugular plasma. Infusion of CGRP can induce headache attacks in migraine and cluster patients. Inhibition of the CGRP signal system is therapeutic in migraine and cluster headache. CGRP is a potent dil...
Pain in trigeminal areas is driven by nociceptive trigeminal afferents. Transduction molecules, among them the nonspecific cation channels transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), which are activated by endogenous and exogenous ligands, are expressed by a significant population of trigeminal nociceptors innervating me...
Background:
The α1 -adrenoceptor agonist, phenylephrine, is used at high concentrations as a mydriatic agent and for the treatment of nasal congestion. Among its adverse side effects transient burning sensations are reported indicating activation of the trigeminal nociceptive system.
Methods:
Neuropeptide release, calcium imaging and meningeal b...
In randomised controlled trials (RCTs) of oral drug treatment of migraine attacks, efficacy is evaluated after 2 hours. The effect of oral naratriptan 2.5 mg with a maximum blood concentration (Tmax) at 2 hours increases from 2 to 4 hours in RCTs. To check whether such a delayed effect is also present for other oral antimigraine drugs, we hand‐sear...
Olfactory and trigeminal chemosensory systems reside in parallel within the mammalian nose. Psychophysical studies in people indicate that these two systems interact at a perceptual level. Trigeminal sensations of pungency mask odour perception, while olfactory stimuli can influence trigeminal signal processing tasks such as odour localization. Whi...
Neben den anatomischen Grundlagen ist das Verständnis der Physiologie der Erregungsleitung (ins-besondere im trigeminalen System), des Schmerzes und der Wundheilung von Bedeutung für den zahnärztlichen Alltag. Verschiedene Botenstoffe dienen der Weiterleitung der nozizeptiven Signale, die dann zentral verarbeitet und im Gehirn zum Schmerzempfinden...
Background
Migraine therapy with sumatriptan may cause adverse side effects like pain at the injection site, muscle pain, and transient aggravation of headaches. In animal experiments, sumatriptan excited or sensitized slowly conducting meningeal afferents. We hypothesized that sumatriptan may activate transduction channels of the “irritant recepto...
Olfactory and trigeminal chemosensory systems reside in parallel within the mammalian nose. Psychophysical studies in people indicate that these two systems interact at a perceptual level. Trigeminal sensations of pungency mask odour perception, while olfactory stimuli can influence trigeminal signal processing tasks such as odour localization. Whi...
Introduction:
Migraine is characterized by cycling phases (interictal, preictal, ictal and postictal) with differing symptoms, while in chronic tension type headache pain phases are fluctuating. The question we asked is whether these phases are associated with changes in parameters of somatosensation and axon-reflex erythema.
Methods:
Patients w...
Background:
Meningiomas are generally slowly growing intracranial tumors. They are often incidentally diagnosed, given that symptoms may be absent even in cases of an enormous tumor size. Headache is a frequent but not consistent symptom. Therefore, we examined the association between structural, biochemical and histochemical tumor parameters with...
Introduction:
The trigeminal ganglion is unique among the somatosensory ganglia regarding its topography, structure, composition and possibly some functional properties of its cellular components. Being mainly responsible for the sensory innervation of the anterior regions of the head, it is a major target for headache research. One intriguing que...
Cutaneous afferent nerves convey sensory information from the external, visceral nerves from the internal environment. The saphenous nerve arising from lumbar dorsal root ganglia and the vagus nerve originating in the nodosum ganglia are prototypic examples of such cutaneous and visceral nerves. Despite a common sensory role, these two nerves have...
Adriamycin is a potent anthracycline-type antitumor agent, but it also exerts potentially serious side effects due to its cardiotoxic and neurotoxic propensity. Multiple impairments in sensory nerve functions have been recently reported in various rat models. The present experiments were initiated in an attempt to reveal adriamycin-induced changes...
Background:
Calcitonin gene-related peptide (CGRP) has long been a focus of migraine research, since it turned out that inhibition of CGRP or CGRP receptors by antagonists or monoclonal IgG antibodies was therapeutic in frequent and chronic migraine. This contribution deals with the questions, from which sites CGRP is released, where it is drained...
Background
Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors...
Retrograde fluorescent labeling of dental primary afferent neurons (DPANs) has been described in rats through crystalline fluorescent DiI, while in the mouse, this technique was achieved with only Fluoro-Gold, a neurotoxic fluorescent dye with membrane penetration characteristics superior to the carbocyanine dyes. We reevaluated this technique in t...
Background/purpose
Hydrogen sulfide (H2S) is a neuromodulator acting through nitroxyl (HNO) when it reacts with nitric oxide (NO). HNO activates transient receptor potential channels of the ankyrin type 1 (TRPA1) causing release of calcitonin gene-related peptide from primary afferents. Activation of meningeal nociceptors projecting to the human sp...
The trigeminal system conveys sensory information from extra- and intracranial structures to the central nervous system via the fifth cranial nerve. The trigeminal ganglion is located extracranially in the Meckel's space. It is subdivided into the ophthalmic (V1), maxillary (V2) and mandibular (V3) division, and contains the cell bodies of the resp...
Pathophysiological concepts of primary headache diseases have been developed significantly in the last decades. Nevertheless pathophysiology of single diseases is unexplained. Migraine headache arises from activation and sensibilization of trigeminal nociceptors, essential processes are located at the meninges and the meningeal vessels. Calcitonin...
Primary headaches may be accompanied by increased intracranial blood flow induced by the release of the potent vasodilator calcitonin gene-related peptide (CGRP) from activated meningeal afferents. We aimed to record meningeal and medullary blood flow simultaneously and to localize the sites of CGRP release in rodent preparations in vivo and ex viv...
Many handmade ancient and recent oriental wool carpets show outstanding brilliance and persistence of colour that is not achieved by common industrial dyeing procedures. Anthropologists have suggested the influence of wool fermentation prior to dyeing as key technique to achieve the high dyeing quality. By means of μ -XRF elemental mapping of morda...
Background
The TRP channel ankyrin type 1 (TRPA1) is a nonselective cation channel known to be activated by environmental irritants, cold and endogenous mediators of inflammation. Activation of TRPA1 in trigeminal afferents innervating meningeal structures has recently been suggested to be involved in the generation of headaches.
Methods
Two in vi...
Chemosensation in the mammalian nose comprises detection of odorants, irritants and pheromones. While the traditional view assigned one distinct sub-system to each stimulus type, recent research has produced a more complex picture. Odorants are not only detected by olfactory sensory neurons but also by the trigeminal system. Irritants, in turn, may...
Background
Tension-type headache and other primary headaches may be triggered or aggravated by disorders of pericranial muscles, which is possibly due to convergent or collateral afferent input from meningeal and muscular receptive areas. In rodent models high extracellular concentrations of ATP caused muscle nociception and central sensitization o...
Headaches are believed to arise from the cranial dura mater and large cerebral arteries because stimuli applied to these structures cause exclusively headache-like sensations. The contribution of extracranial structures like head and neck muscles with their trigger points has also been discussed. The convergence of afferent input to the trigemino-c...
Objective:
In this review we attempt to characterize the acute and chronic role of 5-HT2B receptors with regard to meningeal nociception in animal experiments and clinical data targeting migraine therapy.
Background:
Migraine is a common disabling neurovascular primary headache disease, the pathomechanism of which is still unclear. Serotonin (5-...
Das Skelettsystem ist das Hauptstützgewebe des menschlichen Körpers, das sowohl physikalische Funktionen übernimmt (Schutz innerer Organe, Lokomotion) als auch das das zentrale Speicherorgan für Kalzium und Phosphat darstellt. Die Funktionen des Skeletts ergeben sich als komplexes Zusammenspiel zahlreicher individuell geformter Knochen. Trotz der g...
Pharmacotherapy of migraine pain has largely been focused on calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide mainly released from activated primary afferents. CGRP has multiple effects in different central and peripheral systems but its migraine promoting actions are largely unclear. Current clinical and experimental principles ar...
Zusammenfassung
Calcitonin gene-related peptide (CGRP), ein von primären Afferenzen freigesetztes vasoaktives Neuropeptid, steht im Fokus der pharmakologischen Migränetherapie. CGRP hat Wirkungen auf viele zentrale und periphere Funktionen, aber der migränefördernde Wirkungsmechanismus ist unklar. Derzeitige klinische und experimentelle Therapiepri...
Pain research is based broadly on physiological disciplines and its development follows the methodological progress of the era, from classical psychophysiology to electrophysiological investigations at peripheral and central nociceptive systems, single cells and ion channels to modern imaging of nociceptive processing. Physiological pain research i...
Pharmacotherapy of migraine pain has largely been focused on calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide mainly released from activated primary afferents. CGRP has multiple effects in different central and peripheral systems but its migraine promoting actions are widely unclear. Current clinical and experimental principles are...
Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all p...
Meningeal blood flow is controlled by calcitonin gene-related peptide (CGRP) released from trigeminal afferents and nitric oxide (NO) mainly produced in arterial endothelium. The vasodilatory effect of NO may be due to the NO sibling nitroxyl (HNO), generated through the reaction with hydrogen sulfide (H2 S). We investigated the involvement of HNO...
Clinical human and experimental animal studies have facilitated our understanding of the essential structures in the initiation, transmission, modulation, and maintenance of headache. Pain-sensitive cranial structures, such as the dura mater encephali and large intracerebral blood vessels, and the cranial and cervical muscles and ligaments, which a...
Activity-dependent processes in slowly conducting afferents have been shown to modulate conduction and receptive properties but it is not known how the frequency of action potential firing determines the responses of such fibres to mechanical stimulation. We examined the responses of slowly conducting meningeal afferents to mechanical stimuli and t...
Nitroxyl (HNO) is a redox sibling of nitric oxide (NO) that targets distinct signalling pathways with pharmacological endpoints of high significance in the treatment of heart failure. Beneficial HNO effects depend, in part, on its ability to release calcitonin gene-related peptide (CGRP) through an unidentified mechanism. Here we propose that HNO i...
Objective:
To investigate the efficacy of conservative dental treatment (occlusal splint and pharmacologic therapy) and invasive therapy (prosthetic restorations) in the treatment of tension-type headache (TTH).
Method and materials:
The study sample was composed of 70 patients who presented with symptomatic TTH and were assigned to three treatm...
Objective
To re-investigate the innervation pattern of the dura mater of rat and human middle cranial fossa, the morpho-functional substrate of headache generation, including adjacent extracranial tissues using neuronal in vitro tracing.Background
This study was initiated by recent structural and functional findings of meningeal afferent fibers tha...
CGRP is contained in a substantial proportion of unmyelinated trigeminal neurons innervating intracranial tissues. Previously, we have described a hemisected rodent scull preparation and later the intact trigeminal ganglion to measure stimulated CGRP release from trigeminal afferents.
Here, we establish a preparation for examining CGRP release from...
Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin i...
The calcitonin-gene-related peptide (CGRP) receptor is a heterodimer of calcitonin-receptor-like receptor (CLR) and receptor-activity-modifying protein 1 (RAMP1). Despite the importance of CGRP in regulating gastrointestinal functions, nothing is known about the distribution and function of CLR/RAMP1 in the esophagus, where up to 90 % of spinal aff...
Purpose:
The aim of this study was to assess the long-term reliability of Locator-retained mandibular or maxillary overdentures and to examine clinical and radiographic parameters of the supporting implants.
Materials and methods:
The authors performed a retrospective analysis of a case series. After implant placement and a submerged healing pha...
Cutaneous mastocytosis (CM) has been associated with urticaria, itching, and pain of the affected regions. Although the occurrence of CM in the facial skin is rare, it may be a cause of chronic facial pain, and pain characteristics may mistakenly be interpreted as trigeminal nerve pathology. However, the dermatological appearance of the different v...
Nitric oxide (NO) is thought to play an important role in the pathophysiology of migraine. Infusion of the nitrovasodilator glyceroltrinitrate (nitroglycerin, GTN), which mobilizes NO in the organism, is an approved migraine model in humans. Calcitonin gene-related peptide (CGRP) is regarded as another key mediator in migraine. Increased plasma lev...
Hydrogen sulfide (H2S) emerged recently as an important signaling molecule involved in regulation of blood pressure and neuronal activity. Additionally, H2S and its donors possess huge pharmacological potential to prevent ischemia-reperfusion injuries and, as it has been speculated, to induce suspended animation-like state in small animals. However...
Headaches can be evoked by activation of meningeal nociceptors but an involvement of pericranial tissues is debated. We aimed to examine a possible extracranial innervation by meningeal afferents in the rat. For in vivo neuronal tracing dextran amines were applied to the periosteum underlying the temporal muscle. Labeling was observed two days late...
Patients undergoing cancer chemotherapy are living longer and with better quality of life, and they require dental care both during and after their treatments. Bisphosphonates have been associated with drug-related osteonecrosis of the jaw (ONJ) since the discoveries of Marx in 2003 and Ruggiero and Woo in 2008. Recent literature has indicated a si...
Calcitonin gene‐related peptide (CGRP) and metabolic products of nitric oxide (NO) are increased in jugular venous plasma during migraine attacks and other primary headaches. Patients suffering from primary headaches are particularly sensitive to CGRP and NO donors responding with delayed headaches to an infusion of either of these substances. Acco...
Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. Activation and inhibition of CGRP receptors in the...
The passage of an action potential along a peripheral axon modulates the conduction velocity of subsequent action potentials. In C-neurones with unmyelinated axons repetitive activity progressively slows axonal conduction velocity and in microneurographic recordings from healthy human subjects the magnitude of this slowing can be used to predict th...
Neuropeptides, such as calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) are considered important mediators in primary headaches. Increased concentrations of CGRP have been found in jugular venous plasma during attacks of migraine and, concomitant with VIP elevation, during cluster headache. Substance P...
Although an interaction of malocclusion, parafunction, and temporomandibular joint disorders (TMD) can be inferred from the experience of daily practice, scientific evidence to corroborate this hypothesis does not exist. However, there are indications that TMD and headaches may be intertwined.
The purpose of this study was to identify the presence...
The neuropeptides substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) have been considered as important mediators in migraine and other primary headaches. CGRP and VIP have been found at increased concentrations in jugular venous plasma during attacks of migraine or cluster headache, and CGRP receptor ant...
