A5089345616- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Neuropeptides and Animal Physiology
- Neuroendocrine regulation and behavior
- Ion channel regulation and function
- Musculoskeletal pain and rehabilitation
- Veterinary Pharmacology and Anesthesia
- Ion Channels and Receptors
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Nerve injury and regeneration
- Exercise and Physiological Responses
- Botulinum Toxin and Related Neurological Disorders
- Cannabis and Cannabinoid Research
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Protein Degradation and Inhibitors
- Genetics and Neurodevelopmental Disorders
- Neuroscience of respiration and sleep
- Myofascial pain diagnosis and treatment
- Neuroscience and Neural Engineering
- Circadian rhythm and melatonin
- Sleep and Wakefulness Research
- Pain Management and Placebo Effect
- Allergic Rhinitis and Sensitization
Heidelberg University
2016-2025
University Hospital Heidelberg
2019-2024
Abstract The physiological functions of mast cells remain largely an enigma. In the context barrier damage, are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion allergens, toxins and parasites trigger future antigen avoidance 1–3 . Here, we show that antigen-specific behaviour inbred mice 4,5 is critically dependent on cells; hence, identify immunological sensor cell linking recognition to...
Abstract Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated neuronal formation central nervous system, but neither its involvement pathological nor tested. Here we report a form neuroglia signalling involving astrocytic glycogen dynamics triggered by persistent noxious stimulation via upregulation Protein Targeting to Glycogen (PTG)...
Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets after repeated dosage. Analgesic to vivo could be caused agonist-induced downregulation intracellular trafficking cannabinoid receptors, but little known about molecular mechanisms involved. We show here type 1 receptor (CB ) interacts physically with G-protein-associated sorting protein (GASP1), a sorts receptors lysosomal compartments destined for...
Synaptic long-term potentiation (LTP) at spinal neurons directly communicating pain-specific inputs from the periphery to brain has been proposed serve as a trigger for pain hypersensitivity in pathological states. Previous studies have functionally implicated NMDA receptor-NO pathway and downstream second messenger, cGMP, these processes. Because cGMP can broadly influence diverse ion-channels, kinases, phosphodiesterases, pre- well post-synaptically, precise identity of targets mediating...
Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at sub-cellular level, and related synaptic cognitive phenotypes are unexplored. Here, we probed consequences mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, N-methyl-D-aspartate (NMDAR) function, behavioral second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, found that was significantly more mobile...
Background There is an urgent need to develop and incorporate novel behavioral tests in classically used preclinical pain models. Most rodent studies are based upon stimulus-evoked hindpaw measurements even though chronic usually a day night experience. Chronic indeed debilitating condition that influences the sociability ability for voluntary tasks, but relevant readouts these aspects mostly under-represented literature. Moreover, we lack standardization most paradigms guarantee...
Below-level central neuropathic pain (CNP) affects a large proportion of spinal cord injured individuals. To better define the dynamic changes neural network contributing to development CNP after injury (SCI), we characterized morphological and behavioral correlates in female C57BL/6 mice moderate T11 contusion SCI (50 kdyn) influence physical activity. Compared with sham-operated animals, developed mechanical allodynia 2 weeks post when tested small-diameter von Frey hair filaments (0.16 g...
Most preclinical pain models rely on short-duration stimulus-evoked hind paw measurements even though chronic is usually a day and night experience. Pain debilitating condition that influences the sociability ability for voluntary tasks, but relevant behavioral readouts these aspects are mostly underrepresented in literature. Moreover, we lack standardization most paradigms. Important herewith combination duration of particular tasks effects social environment. We aimed at thoroughly...
Abstract Background Pain can be one of the most severe symptoms associated with multiple sclerosis (MS) and develops varying levels time courses. MS-related pain is difficult to treat, since very little known about mechanisms underlying its development. Animal models experimental autoimmune encephalomyelitis (EAE) mimic many aspects MS are well-suited study pathophysiological mechanisms. Yet, date sensory abnormalities in different EAE models. We therefore aimed thoroughly characterize...
Chronic pain is often accompanied by comorbidities like anxiety and depression. The temporal correlations, as well the underlying mechanisms of these reciprocal are unclear. Moreover, preclinical studies examining emotional behaviour very controversial, a chronological analysis anxiety-like in mouse models considering both genders has not been performed so far.We used several behavioural tests to assess validate complete Freund's adjuvant (CFA) spared nerve injury (SNI) C57BL/6 mice. Among...
Abstract Rodent behavior is affected by different environmental conditions. These do not only comprise experimental and housing conditions but also familiarization with the experimenter. However, specific effects on pain-related chronic pain have been examined. Therefore, we aimed to investigate impact of conditions, using individually ventilated standard open top cages, inverted day-night cycles, experimenter male mice following peripheral neuropathy spared nerve injury (SNI) model. Using a...
Peripheral injury or inflammation leads to a release of mediators capable binding variety ion channels and receptors. Among these are the 7-transmembrane receptors (G protein-coupled receptors) coupling G(s), G(i/o), G₁₂/₁₃, G(q/11) G proteins. Each receptor pathways is involved in nociceptive modulation pain processing, but relative contribution individual signaling vivo has not yet been worked out. The G(q)/G₁₁ branch particular interest because it activation phospholipase C-β, protein...
Abstract Painful neuropathy is a frequent complication in diabetes. Proopiomelanocortin (POMC) an endogenous opioid precursor peptide, which plays protective role against pain. Here, we report dysfunctional POMC-mediated antinociception sensory neurons In streptozotocin-induced diabetic mice the Pomc promoter repressed due to increased binding of NF-kB p50 subunit, leading loss basal POMC level peripheral nerves. Decreased levels are also observed nervous system tissue from patients. The...
The peptide endothelin-1 (ET1), which was originally identified as a vasoconstrictor, has emerged critical regulator of number painful conditions, including inflammatory pain and tumor-associated pain. There is considerable pharmacological evidence supporting role for endothelin A receptors (ETA) in mediating ET1-induced pro-algesic functions. ETA are expressed small-diameter nociceptive neurons, but also found variety other cell types peripheral tissues, immune cells, keratinocytes,...
Background: Group I metabotropic glutamate receptor (mGluR1/5) signaling is an important mechanism of pain-related plasticity in the amygdala that plays a key role emotional-affective dimension pain. Homer1a, short form Homer1 family scaffolding proteins, disrupts mGluR-signaling complex and negatively regulates nociceptive at spinal synapses. Using transgenic mice overexpressing Homer1a forebrain (H1a-mice), we analyzed synaptic plasticity, pain behavior mGluR1 function basolateral (BLA)...
The rich diversity of lipids and the specific signalling pathways they recruit provides tremendous scope for modulation biological functions. Lysophosphatidylinositol (LPI) is emerging as a key modulator cell proliferation, migration, function, holds important pathophysiological implications due to its high levels in diseased tissues, such cancer. Here we report novel role LPI sensitization peripheral sensory neurons, which was evident exaggerated sensitivity painful innocuous pressure....
Abstract Mechanically silent nociceptors are sensory afferents that insensitive to noxious mechanical stimuli under normal conditions but become sensitized such during inflammation. Using RNA-sequencing and quantitative RT-PCR we demonstrate inflammation upregulates the expression of transmembrane protein TMEM100 in electrophysiology revealed over-expression is required sufficient un-silence mice. Moreover, show mice lacking do not develop secondary hypersensitivity—i.e., pain...
Abstract Low back pain (LBP) is a highly prevalent and disabling condition whose initiating factors are poorly understood. It known that psychological physical stress associated with LBP but the causal relationship, mechanisms, mediators have not been elucidated, preclinical model enabling investigation of causality thereby critically contributing to clinical translation does exist. In this study, we first established characterized myofascial in mice based on nerve growth factor (NGF)...
Chronic stress enhances the risk of neuropsychiatric disorders and contributes to aggravation chronicity pain. The development stress-associated diseases, including pain, is affected by individual vulnerability or resilience stress, although mechanisms remain elusive. We used repeated social defeat model promoting susceptible resilient phenotypes in male female mice induced knee mono-arthritis investigate impact on pain immune system regulation. analyzed different pain-related behaviors,...