A5020841776- Pain Mechanisms and Treatments
- Nerve injury and regeneration
- Ion channel regulation and function
- Botulinum Toxin and Related Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Healthcare and Venom Research
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Neuroendocrine regulation and behavior
- Hereditary Neurological Disorders
- Stress Responses and Cortisol
- Spine and Intervertebral Disc Pathology
- Musculoskeletal pain and rehabilitation
- Functional Brain Connectivity Studies
- EEG and Brain-Computer Interfaces
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neural Engineering
- Neuropeptides and Animal Physiology
- Glioma Diagnosis and Treatment
- Biomedical and Engineering Education
- Nerve Injury and Rehabilitation
- Evolutionary Psychology and Human Behavior
- Metabolism, Diabetes, and Cancer
- Inflammasome and immune disorders
- Ubiquitin and proteasome pathways
University of Lausanne
2013-2024
University Hospital of Lausanne
2009-2017
Ann Arbor Center for Independent Living
2006
University of Michigan–Ann Arbor
2006
Experimental models of peripheral nerve injury have been developed to study mechanisms neuropathic pain. In the spared (SNI) model in rats, common peroneal and tibial nerves are injured, producing consistent reproducible pain hypersensitivity territory sural nerve. this study, we investigated whether SNI mice is also a valid system for results significant decrease withdrawal threshold SNI-operated mice. The effect very between animals persists four weeks study. We determined relative...
Background Gene transfer to nociceptive neurons of the dorsal root ganglia (DRG) is a promising approach dissect mechanisms pain in rodents and potential therapeutic strategy for treatment persistent disorders such as neuropathic pain. A number studies have demonstrated transduction DRG using herpes simplex virus, adenovirus more recently, adeno-associated virus (AAV). Recombinant AAV are currently gene vehicles choice nervous system several advantages over other vectors, including stable...
Peripheral neuropathic pain is a disabling condition resulting from nerve injury. It characterized by the dysregulation of voltage-gated sodium channels (Navs) expressed in dorsal root ganglion (DRG) sensory neurons. The mechanisms underlying altered expression Na(v)s remain unknown. This study investigated role E3 ubiquitin ligase NEDD4-2, which known to ubiquitylate Navs, pathogenesis mice. spared injury (SNI) model traumatic injury-induced was used, and an Na(v)1.7-specific inhibitor,...
Microglia, resident immune cells in the central nervous system, play a role neuroinflammation and development of neuropathic pain. We found that stimulator interferon genes (STING) is predominantly expressed spinal microglia upregulated after peripheral nerve injury. However, mechanical allodynia, as marker pain following injury, did not require microglial STING expression. In contrast, activation by specific agonists (ADU-S100, 35 nmol) significantly alleviated male mice, but female mice....
Current evidence indicates that p38 mitogen-activated protein kinase activation in spinal microglia contributes to the development of neuropathic pain. However, how nerve injury activates is incompletely unknown. Nerve injury-induced ectopic spontaneous activity essential for generation The authors examined whether peripheral neural necessary microglia.To examine depends on rat spared (SNI) model, blocked conduction sciatic before or 2 days after SNI. block was produced by applying...
Voltage-gated sodium channel (Na v 1) β2 subunits modulate gating, assembly, and cell-surface expression in CNS neurons vitro vivo . increases sensory after nerve injury, development of mechanical allodynia the spared injury model is attenuated β2-null mice. Thus, we hypothesized that modulates electrical excitability dorsal root ganglion (DRG) We compared currents ( I Na ) small DRG from +/+ −/− mice to determine effects on tetrodotoxin-sensitive (TTX-S) tetrodotoxin-resistant (TTX-R) 1...
The development of abnormal primary sensory neuron excitability and neuropathic pain symptoms after peripheral nerve injury is associated with altered expression voltage-gated sodium channels (VGSCs) a modification currents. To investigate whether the β2 subunit VGSCs participates in generation pain, we used spared (SNI) model rats to examine selectively injured (tibial common peroneal nerves) uninjured (sural nerve) afferents. Three days SNI, immunohistochemistry Western blot analysis...
Background: Dysregulation of voltage-gated sodium channels (Na v s) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization the different isoforms Na s under normal and pathological conditions had never been performed on mice, despite their widespread use pain research. mRNA levels mouse dorsal root ganglia (DRG) were studied spared injury (SNI) spinal ligation (SNL) models In SNI model, injured...
Voltage-gated sodium channels (Navs) are glycoproteins composed of a pore-forming α-subunit and associated β-subunits that regulate Nav plasma membrane density biophysical properties. Glycosylation the also directly affects Navs gating. glycosylation thus comodulate We hypothesized could influence glycosylation. Whole-cell patch clamp HEK293 cells revealed both β1- β3-subunits coexpression shifted V ½ steady-state activation inactivation increased Nav1.7-mediated I Na density. Biotinylation...
Nociceptors are a particular subtype of dorsal root ganglion (DRG) neurons that detect noxious stimuli and elicit pain. Although recent efforts have been made to reveal the molecular profile nociceptors in normal conditions, little is known about how this changes pathological conditions. In study we exploited laser capture microdissection specifically collect individual injured non-injured nociceptive DRG define their gene profiling rat spared nerve injury (SNI) model neuropathic We found...
The immune system is involved in the development of neuropathic pain. In particular, infiltration T-lymphocytes into spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used spared (SNI) model pain Sprague Dawley adult male rats assess proliferation, and/or protein/gene expression levels for microglia (Iba1), (CD2) and cytotoxic (CD8). dorsal horn ipsilateral SNI, Iba1 BrdU stainings revealed microglial reactivity respectively,...
Satellite glial cells (SGCs), enveloping primary sensory neurons' somas in the dorsal root ganglion (DRG), contribute to neuropathic pain upon nerve injury. Glial fibrillary acidic protein (GFAP) serves as an SGC activation marker, though its DRG satellite cell specificity is debated. We employed hGFAP-CFP transgenic mouse line, designed for astrocyte studies, explore expression within peripheral nervous system (PNS) after spared injury (SNI). used diverse immunostaining techniques, Western...
Background: Clinical and experimental studies of neuropathic pain support the hypothesis that a functional coupling between postganglionic sympathetic efferent sensory afferent fibers contributes to pain. We investigated whether pain-related behavior in spared nerve injury (SNI) rat model is dependent on nervous system. Results: Permanent chemical sympathectomy was achieved by daily injection guanethidine (50 mg/kg s.c.) from age P8 P21. SNI performed at adulthood followed 11 weeks...
The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is one of the main sources interleukin-1β (IL-1β) involved in several inflammatory-related pathologies. To date, its relationship with pain has not been studied depth. aim our study was to elucidate role NLRP3 IL-1β production on neuropathic pain. Results showed that basal sensitivity unaltered NLRP3-/- mice as well responses formalin test. Spared nerve injury (SNI) surgery induced development mechanical allodynia...
The antidiabetic drug metformin has been shown to reduce pain hypersensitivity in preclinical models of chronic and neuropathic humans. Multiple intracellular pathways have described as targets. Among them, is an activator the adenosine 5′-monophosphate protein kinase that can turn modulate activity E3 ubiquitin ligase NEDD4-2 thus post-translational expression voltage-gated sodium channels (Na<sub>V</sub>s). In this study, we found bulk effect on Na1.7 dependent NEDD4-2. HEK cells,...
SUMMARY Oxytocin orchestrates social and emotional behaviors through modulation of neural circuits in brain structures such as the central amygdala (CeA). The long-standing dogma is that oxytocin signaling nervous system occurs exclusively via direct actions on neurons. However, several findings over last decades showed astrocytes actively participate neuronal circuits. Here, we investigate degree astrocytes’ involvement functions. Using astrocyte’ specific gain loss function approaches,...