A5036931222- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Complement system in diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuropeptides and Animal Physiology
- Biochemical effects in animals
- Ion Channels and Receptors
- Neurobiology and Insect Physiology Research
- Photochromic and Fluorescence Chemistry
- Malaria Research and Control
- Glycogen Storage Diseases and Myoclonus
- Pharmacological Effects of Natural Compounds
- Immune cells in cancer
- Molecular Sensors and Ion Detection
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Photoreceptor and optogenetics research
- Thermoregulation and physiological responses
King's College London
2017-2024
St. Thomas Hospital
2022
St Thomas' Hospital
2022
Clayton State University
2022
The King's College
2022
Central Institute of Medicinal and Aromatic Plants
2022
The London College
2022
Guy's and St Thomas' NHS Foundation Trust
2022
Institut de Génomique Fonctionnelle
2011-2013
Inserm
2012-2013
Blocking HCN2 ion channel activity in peripheral nociceptive neurons alleviates the pain hypersensitivity associated with diabetic neuropathy.
Metabotropic glutamate (mGlu) receptors are promising targets to treat numerous brain disorders. So far, allosteric modulators the only subtype selective ligands, but pure agonists still have strong therapeutic potential. Here, we aimed at investigating possibility of developing subtype-selective by extending glutamate-like structure hit a nonconsensus binding area. We report properties first mGlu4-selective orthosteric agonist, derived from virtual screening hit, LSP4-2022 using cell-based...
Hyperactivity of the glutamatergic system is involved in development central sensitization pain neuraxis, associated with allodynia and hyperalgesia observed patients chronic pain. Herein we study ability type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal signaling alleviate We show that mGlu4 are located both on unmyelinated C-fibers neurons terminals inner lamina II cord where they inhibit transmission through coupling Cav2.2 channels. Genetic deletion mice alters...
Abstract Rheumatoid arthritis-associated pain is poorly managed, often persisting when joint inflammation pharmacologically controlled. Comparably, in the mouse K/BxN serum-transfer model of inflammatory arthritis, hind paw nociceptive hypersensitivity occurs with ankle swelling (5 days after immunisation) has resolved (25 immunisation). In this study, lipid mediator (LM) profiling lumbar dorsal root ganglia (DRG), site sensory neuron cell bodies innervating joints, 5 and 25 serum transfer...
Prolonged exposure to opioids causes an enhanced sensitivity painful stimuli (opioid-induced hyperalgesia, OIH) and a need for increased opioid doses maintain analgesia tolerance, OIT), but the mechanisms underlying both processes remain obscure. We found that pharmacological block or genetic deletion of HCN2 ion channels in primary nociceptive neurons male mice completely abolished OIH had no effect on OIT. Conversely, inhibition central HCN alleviated OIT OIH. Expression C-FOS, marker...
Abstract Moderate coolness is sensed by TRPM8 ion channels in peripheral sensory nerves, but the mechanism which noxious cold detected remains elusive. Here, we show that somatosensory and sympathetic neurons express two distinct mechanisms to detect cold. In first, inhibition of a background outward current causes membrane depolarization activates an inward through voltage‐dependent calcium (Ca V ) channels. A second cold‐activated independent voltage, inhibited blockers ORAI downregulation...
Abstract Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation innate immune system thought cause a damaging cells into tissues consequent excessive release cytokines, chemokines neutrophil extracellular traps (NETs). In these circumstances, tempering may, paradoxically, promote recovery. Here we identify antimalarial compound artemisinin potent selective inhibitor...
Abstract Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation innate immune system thought cause a damaging cells into tissues consequent excessive release cytokines. In these circumstances, tempering may, paradoxically, promote recovery. Here we identify antimalarial compound artemisinin potent selective inhibitor neutrophil macrophage induced by many chemotactic agents....