A5075809342- Pain Mechanisms and Treatments
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Nerve injury and regeneration
- Circadian rhythm and melatonin
- Pharmacology and Obesity Treatment
- Botulinum Toxin and Related Neurological Disorders
- Nicotinic Acetylcholine Receptors Study
- Neuropeptides and Animal Physiology
- Neural dynamics and brain function
- Spinal Cord Injury Research
- Receptor Mechanisms and Signaling
- Tactile and Sensory Interactions
- Mesenchymal stem cell research
- Advanced Fluorescence Microscopy Techniques
- Pediatric Pain Management Techniques
- Neuroscience and Neural Engineering
- Adipose Tissue and Metabolism
- Spaceflight effects on biology
- Cancer, Stress, Anesthesia, and Immune Response
- Mindfulness and Compassion Interventions
- Advanced Sensor and Energy Harvesting Materials
- Dietary Effects on Health
- Optical Imaging and Spectroscopy Techniques
University of Oxford
2021-2025
Institut de Neurosciences de la Timone
2021-2023
Aix-Marseille Université
2021-2023
Centre National de la Recherche Scientifique
2023
Science Oxford
2023
John Radcliffe Hospital
2021
Université Laval
2016-2020
Imagerie et Cerveau
2020
Institut Universitaire en Santé Mentale de Québec
2013-2017
Emory University
2013
Abstract While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic at late remains unknown. Here, we show that activation the cord persists for >3 months following nerve injury rodents, beyond involvement proinflammatory cytokine and chemokine signalling. In this phase, selective depletion male rats with targeted immunotoxin Mac1-saporin blockade brain-derived neurotrophic factor–TrkB signalling intrathecal TrkB Fc...
C-low threshold mechanoreceptors (C-LTMRs) in animals (termed C-tactile (CT) fibres humans) are a subgroup of C-fibre primary afferents, which innervate hairy skin and respond to low-threshold punctate indentations brush stimuli. These afferents gentle touch stimuli implicated mediating pleasant/affective touch. have traditionally been studied using low-throughput, technically challenging approaches, including microneurography humans teased fibre electrophysiology other mammals. Here we...
GABAA/glycine-mediated neuronal inhibition critically depends on intracellular chloride (Cl-) concentration which is mainly regulated by the K+-Cl- co-transporter 2 (KCC2) in adult central nervous system (CNS). KCC2 heterogeneity thus affects information processing across CNS areas. Here, we uncover a gradient Cl- extrusion capacity superficial dorsal horn (SDH) of spinal cord (laminae I-II: LI-LII), remains concealed under low load. Under high load or heightened synaptic drive, lower...
Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with persistent pain. Chemogenetics has shown promise as a means suppress such excitability, yet chemogenetic approaches suitable for human applications are needed. PSAM 4 -GlyR modular system based on α7 nicotinic acetylcholine and glycine receptors, which responds inert chemical ligands clinically approved drug varenicline. Here, we demonstrated efficacy this channel silencing both mouse by...
Activation of the mechanistic/mammalian target rapamycin (mTOR) kinase in models acute and chronic pain is strongly implicated mediating enhanced translation hyperalgesia. However, molecular mechanisms by which mTOR regulates nociception remain unclear. Here we show that deletion eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a major downstream effector, represses eIF4E activity cap-dependent translation, leads to mechanical, but not thermal hypersensitivity. Mice lacking 4E-BP1...
Neuronal inhibition mediated by GABAA receptors constrains nociceptive processing in the spinal cord, and loss of GABAergic can produce allodynia hyperalgesia. Extrasynaptic α5 subunit-containing (α5GABAA Rs) generate a tonic conductance that inhibits neuronal activity learning memory; however, it is unclear whether α5GABAA Rs similarly cord dorsal horn to constrain nociception. We assessed distribution immunohistochemical analysis, function neurons superficial using electrophysiological...
Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive clinical disorders. Its electrophysiological correlate "wind-up," which dorsal horn spinal neurons increase their response repeated nociceptor stimulation. To understand the genetic basis summation, we undertook GWAS wind-up healthy human volunteers found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was...
Abstract C-low threshold mechanoreceptors (C-LTMRs) in animals (termed C-tactile (CT) fibres humans) are a subgroup of C-fibre primary afferents, which innervate hairy skin and respond to low punctate indentations brush stimuli. These afferents gentle, touch stimuli implicated mediating pleasant/affective touch. have traditionally been studied using low-throughput, technically challenging approaches, including microneurography humans teased fibre electrophysiology other mammals. Here we...
Polyamines are regulatory metabolites with key roles in transcription, translation, cell signalling and autophagy1. They implicated multiple neurological disorders including stroke, epilepsy neurodegeneration can regulate neuronal excitability through interactions ion channels2. have been linked to pain showing altered levels human persistent states modulation of behaviour animal models3. However, the systems governing polyamine transport within nervous system remain unclear. In undertaking...
Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in modulation of several modalities information transmission. A well-studied mechanism by which corticospinal projection modulates sensory is primary afferent depolarization, has been characterized fast muscular and cutaneous, but not slow-conducting nociceptive skin afferents. Here we investigated whether inhibition information, produced activation cortex, involves a direct presynaptic C In...
The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres damaged tissue in absence ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well electrical and mechanical cues, offer promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell...
Optogenetics has become an integral tool for studying and dissecting the neural circuitries of brain using optical control. Recently, it also begun to be used in investigation spinal cord peripheral nervous system. However, information on these regions’ properties is sparse. Moreover, there a lack data dependence light propagation with respect tissue organization orientation. This important effective simulations optogenetic planning, particularly where myelinated axons are highly organized....
Poor functional recovery after spinal cord injury (SCI) drives the development of novel strategies to manage this devastating condition. We recently showed promising immunomodulatory and pro-regenerative actions bio-functionalized carbon microfibres (MFs) implanted in a rodent model SCI. In order maximize tissue repair while easing MF implantation, we produced composite implant based on embedding several MFs within fibrin hydrogel. used intravital imaging fluorescent reporter mice at early...
Abstract Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with persistent pain. Chemogenetics has shown promise as a means suppress such excitability, yet chemogenetic approaches suitable for human applications are needed. PSAM 4 -GlyR modular system based on α7 nicotinic acetylcholine and glycine receptors, which responds inert chemical ligands clinically-approved drug, varenicline. Here, we demonstrated efficacy this channel silencing...
Twenty-four hour rhythmicity of liver metabolic and cellular activities is greatly modified by daytime restricted feeding (DRF). The use this protocol has been associated with the study characterization food-entrained oscillator (FEO). aim project was to explore adaptations in hepatic apoptotic activity duplication a 2-h restricted-feeding schedule. Our findings indicate that DRF promoted rise intrinsic pathway apoptosis which dependent mitochondrial cytochrome C release. group synchronized...
Optogenetics is currently one of the most popular technique in neuroscience. It enables cell-selective and temporally-precise control neuronal activity. Good spatial stimulated area minimized tissue damage requires a specific knowledge about light scattering properties. Light propagation cell cultures brain relatively well documented allows for precise reliable delivery to neurons. In spinal cord, must pass through highly organized white matter before reaching bodies present grey matter,...
Abstract Insight into nociceptive circuits will ultimately build our understanding of pain processing and aid the development analgesic strategies. Neural circuit analysis has been advanced greatly by optogenetic chemogenetic tools, which have allowed function to be ascribed discrete neuronal populations. Neurons dorsal root ganglion, include nociceptors, proved challenging targets for manipulation given specific confounds with commonly used DREADD technology. We developed a cre/lox...