A5053573871- Pain Mechanisms and Treatments
- Ion Channels and Receptors
- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Neuropeptides and Animal Physiology
- Nerve injury and regeneration
- Olfactory and Sensory Function Studies
- Botulinum Toxin and Related Neurological Disorders
- Acupuncture Treatment Research Studies
- Enhanced Recovery After Surgery
- Gastrointestinal motility and disorders
- Barrier Structure and Function Studies
- Postharvest Quality and Shelf Life Management
- Nicotinic Acetylcholine Receptors Study
- Dermatology and Skin Diseases
- Cardiac electrophysiology and arrhythmias
- Vagus Nerve Stimulation Research
- Music Therapy and Health
- Exercise and Physiological Responses
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Anesthesia and Pain Management
- Pain Management and Placebo Effect
- Neuroscience of respiration and sleep
- Plant Reproductive Biology
Friedrich-Alexander-Universität Erlangen-Nürnberg
2011-2022
University of Oxford
1997
Loss-of-function mutations of NaV1.7 lead to congenital insensitivity pain, a rare condition resulting in individuals who are otherwise normal except for the inability sense making pharmacological inhibition promising therapeutic strategy treatment pain. We characterized novel mouse model NaV1.7-mediated pain based on intraplantar injection scorpion toxin OD1, which is suitable rapid vivo profiling inhibitors. Intraplantar OD1 caused spontaneous behaviors, were reversed by co-injection with...
Selective targeting of sensory or nociceptive neurons in peripheral nerves remains a clinically desirable goal. Delivery promising analgesic drugs is often impeded by the perineurium, which functions as diffusion barrier attributable to tight junctions. We used perineurial injection hypertonic saline tool open transiently rats and elucidated molecular action principle mechanistic detail: Hypertonic acts via metalloproteinase 9 (MMP9). The noncatalytic hemopexin domain MMP9 binds low-density...
Abstract Background Two transient receptor potential ( TRP ) channels, TRPV1 and TRPA1 , have been physiologically studied with regard to noxious heat transduction. Evidence argues against these channels as sole transducers of or cold, respectively. Moreover, in submammalian species the orthologue shows sensitivity. Methods In vitro single‐fibre compound action recordings from C ‐fibres well measurements stimulated cutaneous CGRP release are combined behavioural experiments assess...
The most widely used formalin test to screen antinociceptive drug candidates is still apostrophized as targeting inflammatory pain, in spite of strong opposing evidence published. In our rat skin-nerve preparation ex vivo, recording from all classes sensory single-fibers (n = 32), 30 units were transiently excited by formaldehyde concentrations 1-100 mM applied receptive fields (RFs) for 3 min, C and Aδ-fibers being more sensitive (1-30 mM) than Aβ-fibers. From on, ~1% the concentration...
Sensory properties of unmyelinated axons in the isolated rat sciatic nerve have been revealed previously by measuring stimulated neuropeptide release response to noxious stimuli. In addition, axonal sensitization inflammatory mediators has demonstrated and shown depend on heat- proton-activated ion channel transient receptor potential vanilloid receptor-1. It was unclear whether this responsiveness is accompanied ectopic generation action potentials, which may play a crucial role painful...
Background: Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme disorder (PEPD). One characteristic these is slowed fast-inactivation kinetics, which may give rise resurgent currents. It long known that toxins from Anemonia sulcata, ATX-II, slow fast inactivation and skin contact for example during diving leads various symptoms itch. Here, we investigated if ATX-II induces currents in sensory neurons...
The sodium channel NaV1.7 contributes to action potential (AP) generation and propagation. Loss-of-function mutations in patients lead congenital indifference pain, though it remains unclear where on the way from sensory terminals central nervous system signalling is disrupted. We confirm that conditional deletion of advillin-expressing neurons leads impaired heat mechanical nociception behavioural tests. With single-fiber recordings isolated skin, we found (1) a significantly lower...
Abstract The upregulation of the tetrodotoxin-resistant voltage-gated sodium channel Na V 1.9 has previously been associated with inflammatory hyperalgesia. Na1.9 knockout (KO) mice, however, did not seem insensitive in conventional tests acute nociception. Using electrophysiological, neurochemical, and behavioral techniques, we now show 1.9-null mice exhibit impaired mechanical thermal sensory capacities reduced electrical excitability nociceptors. In single-fiber recordings from isolated...
GABA depolarized sural nerve axons and increased the electrical excitability of C-fibres via GABAA receptor. Axonal responses to monotonically with rate action potential firing. Action activity in unmyelinated is coupled Na-K-Cl cotransporter type 1 (NKCC1) loading axonal chloride. Activation receptor stabilized C-fibre during prolonged low frequency (2.5 Hz) NKCC1 maintains intra-axonal chloride provide feed-forward stabilization thus support sustained firing.GABAA (GABAA R)-mediated...
Post-operative ileus (POI) is a transient impairment of gastrointestinal (GI) transit that develops after abdominal surgery. The goal this study was to investigate the effect spinal cord stimulation (SCS) on gastric emptying and upper GI in rat model POI. All rats had an electrode placed dorsal surface between T(5) T(8) segments. After recovery, (geometric centre head meal) were assessed using radiolabelled meal fed each via oral gavage. In unanaesthetized rats, SCS (15, 25, 50, 100, 200 Hz,...
Abstract Loss-of-function mutations in the enzyme 7-dehydrocholesterol reductase are responsible for Smith–Lemli–Opitz syndrome, which (7-DHC) levels markedly increased plasma and tissues of patients. This increase 7-DHC is probably associated with painful itchy photosensitivity reported by majority patients syndrome. To identify molecular targets involved activation photosensitization primary afferents 7-DHC, we focused on TRPA1 TRPV1, two ion channels expressed nociceptive nerve endings...
ABSTRACT Distinct sensory properties of unmyelinated axons in the isolated rat sciatic nerve have previously been revealed by measuring stimulated neuropeptide (CGRP) release response to noxious stimuli. Axonal sensitization heat inflammatory mediators has demonstrated and shown depend on heat‐ proton‐activated ion channel TRPV1. Recently, we vitro that stimulation nociceptive generates ectopic action potential discharge which resembles corresponding cutaneous endings. It remained however,...
Key points This study examines conduction in peripheral nerves and its use dependence tetrodotoxin‐resistant (TTXr) sodium channel (Na v 1.8, Na 1.9) knockout wildtype animals. We observed use‐dependent decreases of single fibre compound action potential amplitude mouse C‐fibres (wildtype). matches the previously published hypothesis that increased Na/K‐pump activity is not underlying mechanism for changes neural conduction. Knocking out TTXr channels influences conductive properties (action...
Abstract Background Injection of the noxious peptide Bv8 has previously been shown to induce a biphasic thermal hyperalgesia in rodents, first peak presumably due peripheral sensitization. This hypothesis never directly confirmed. We have assessed whether can indeed sensitize nerve fibres mouse heat. Methods used recordings from single cutaneous fibres, calcitonin gene‐related (CGRP) release and immunostaining nerves plantar skin evaluate effects on nerves. Results Application at nanomolar...
Abstract Cutaneous afferent nerves convey sensory information from the external, visceral internal environment. The saphenous nerve arising lumbar dorsal root ganglia and vagus originating in nodosum are prototypic examples of such cutaneous nerves. Despite a common role, these two have distinct embryonic origin vary neuropeptide expression. Because their physiological roles, it is plausible that they differ also conductive properties. We tested calcitonin gene‐related peptide (CGRP) release...
Fragestellung Musiktherapie (MT) ist in der Palliativmedizin weit verbreitet, unter anderem zu Verringerung Schmerzwahrnehmung u. Steigerung von Wohlbefinden. Die Analyse Herzraten-Variabilität (HRV) gibt Einblick physiologische Reaktionen, die Surrogatparameter für Schmerz oder Angst deren Beeinflussung z. B. durch MT sind.