A5034896945- Pain Mechanisms and Treatments
- Ion channel regulation and function
- Ion Channels and Receptors
- Exercise and Physiological Responses
- Ion Transport and Channel Regulation
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Stress Responses and Cortisol
- Dermatology and Skin Diseases
- Sphingolipid Metabolism and Signaling
- Virus-based gene therapy research
- Allergic Rhinitis and Sensitization
- Photoreceptor and optogenetics research
- RNA regulation and disease
- Urticaria and Related Conditions
- Veterinary Pharmacology and Anesthesia
- Olfactory and Sensory Function Studies
- Protease and Inhibitor Mechanisms
- Retinal Development and Disorders
- Wnt/β-catenin signaling in development and cancer
- Cardiac electrophysiology and arrhythmias
- Sleep and Wakefulness Research
- Cancer-related gene regulation
- Receptor Mechanisms and Signaling
Universitat de Barcelona
2013-2025
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2011-2025
University of Cambridge
2017-2024
Max Delbrück Center
2024
Lawn Tennis Association
2018-2020
University of St. Gallen
2015
Objective Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology organism behaviour. Colonic sensory neurons activate reflex pathways give rise to conscious sensation, but diversity division function within these is poorly understood. The identification signalling contributing visceral sensation constrained by a paucity molecular markers. Here we address this comprehensive transcriptomic profiling unsupervised clustering individual...
Background: Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K + channel (analogous to TREK-1 in mammals) plays critical role of determining neuronal excitability following nerve injury. Few data are available on 2P channels after peripheral axotomy mammals. Results: Here we describe that rat sciatic induces L4-L5 DRG sensory neurons decreases TRESK (K2P18.1) expression, with major contribution total...
In Brief Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation ocular dryness, whose underlying neural mechanisms remain unknown. Removal main lachrymal gland in guinea pigs caused long-term reduction basal tearing accompanied by changes architecture density subbasal corneal nerves epithelial terminals. After 4 weeks, ongoing impulse activity responses to cooling cold thermoreceptor endings were enhanced. Menthol (200 μM) first excited then...
Abstract The pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical tests in animal models of painful conditions represent one the earliest checkpoints novel therapeutics must negotiate before consideration human use. Traditionally, pain status laboratory animals has been inferred from evoked nociceptive assays that measure their responses to noxious stimuli. disconnect between how tested and it experienced by humans may part explain shortcomings current...
Sensory nerve fibers innervating the ocular anterior surface detect external stimuli producing innocuous and painful sensations. Protons are among first mediators released by damaged cells during inflammation, tissue injury, or other chronic ophthalmic conditions. We studied whether acid-sensing ion channels (ASICs) expressed in corneal sensory neurons their roles response to moderate acidifications of pathologies inflammation. Moderate acidic pH (6.6) activated ASIC-like currents neurons,...
Ongoing, spontaneous pain is characteristic of inflammatory joint and reduces an individual's quality life. To understand the neural basis pain, we made a unilateral knee injection complete Freund's adjuvant (CFA) in mice, which reduced their natural digging behavior. We hypothesized that sensitization knee-innervating dorsal root ganglion (DRG) neurons underlies this altered test hypothesis, performed electrophysiological recordings on retrograde labeled primary DRG neuron cultures measured...
Abstract A subset of peripheral sensory neurons expressing specific Mas-related G-protein–coupled receptors and transient receptor potential channels mediate pruritogen-induced chemical itch. However, the molecular mechanisms that regulate excitability these cells, consequently itch sensation, are poorly understood. TWIK-related spinal cord K + channel (TRESK) is a background modulates resting membrane potential, action firing, neuronal excitability, it has been involved in somatosensation...
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy caused by mutations in either MLC1 or GLIALCAM genes and associated myelin astrocyte vacuolation. It has been suggested that MLC impaired cell volume regulation as result defective activation astrocytic volume-regulated anion currents (VRAC). GlialCAM brings the ClC-2 Cl− channel to cell–cell junctions, even though role disease remains incompletely understood. To gain insights into biological...
Key points TRESK background K + channel is expressed in sensory neurons and acts as a brake to reduce neuronal activation. Deletion of the enhances excitability nociceptors. Skin nociceptive C‐fibres show an enhanced activation by cold mechanical stimulation knockout animals. Channel deletion selectively sensitivity mice, without altering heat. These results indicate that regulates specific subpopulations involved mechanosensitivity cold‐sensing. Abstract Background potassium‐permeable ion...
Objective Joint pain is the major clinical symptom of arthritis that affects millions people. Controlling excitability knee‐innervating dorsal root ganglion ( DRG ) neurons (knee neurons) could potentially provide relief. We undertook this study to evaluate whether newly engineered adeno‐associated virus AAV serotype, ‐ PHP .S, can deliver functional artificial receptors control knee neuron following intraarticular injection. Methods The .S virus, packaged with dT omato fluorescent protein...
Abstract Pain is a principal contributor to the global burden of arthritis with peripheral sensitization being major cause arthritis-related pain. Within knee joint, distal endings dorsal root ganglion neurons (knee neurons) interact fibroblast-like synoviocytes (FLS) and inflammatory mediators they secrete, which are thought promote sensitization. Correspondingly, RNA sequencing has demonstrated detectable levels proinflammatory genes in FLS derived from patients. This study confirms that...
By endowing light control of neuronal activity, optogenetics and photopharmacology are powerful methods notably used to probe the transmission pain signals. However, costs, animal handling ethical issues have reduced their dissemination routine use. Here we report LAKI (Light Activated K+ channel Inhibitor), a specific photoswitchable inhibitor pain-related two-pore-domain potassium TREK TRESK channels. In dark or ambient light, is inactive. alternating transdermal illumination at 365 nm 480...
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy caused by mutations in either MLC1 or GLIALCAM. GlialCAM necessary for the correct targeting MLC1, but also Cl- channel ClC-2. Furthermore, modifies ClC-2 functional properties vitro. However, vivo studies GlialCAM-/- mice have shown that modification activity only occurs oligodendrocytes, despite and being expressed astrocytes. Thus, relationship between GlialCAM, astrocytes unknown. Here, we...
By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such have normal sensory and psychometric test results, except for significantly higher cuff pressure We find an excess of heterozygotes carrying the rare allele SNP rs140124801 in KCNG4. The variant KV6.4-Met419 has a dominant-negative effect cannot modulate voltage dependence KV2.1 inactivation because it fails to traffic plasma membrane. In vivo, Kcng4 (KV6.4)...
The two-pore domain K+ channel TRESK is expressed in dorsal root ganglion and trigeminal sensory neurons where it a major contributor to background current. acts as break prevent excessive neuron activation decreases its expression or function have been involved neuronal hyperexcitability after injury/inflammation, migraine altered perception (tingling, cooling pungent burning sensations). All these effects implicated this nociception mechanotransduction. To determine the role of...
Pyrethroid insecticides are widely used for pest control in agriculture or human public health commonly as a topical treatment scabies and head lice. Exposure to pyrethroids such permethrin tetramethrin (TM) causes sensory alterations transient pain, burning, stinging sensations, paraesthesias. Despite the well-known effects of on sodium channels, actions other channels that neuron excitability less studied. Given role 2-pore domain potassium (K2P) modulating firing, both physiological...
Arthritic conditions are a major source of chronic pain. Furthering our understanding disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements pH in human synovial fluid suggest that acidosis occurs, but this is highly variable between individuals. Here we sought determine if tissue occurs widely used rodent model: complete Freund's adjuvant (CFA)‐induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant...
Acid-sensing ion channels (ASICs) form both homotrimeric and heterotrimeric that are activated by extracellular protons involved in a wide range of physiological pathophysiological processes, including pain anxiety. ASIC proteins can channels. The ASIC3 subunit has been shown to be particular importance the peripheral nervous system with pharmacological genetic manipulations demonstrating role pain. Naked mole-rats, despite having functional ASICs, insensitive acid as noxious stimulus show...
Acid-sensing ion channels (ASICs) are voltage-independent cation that detect decreases in extracellular pH. Dysregulation of ASICs underpins a number pathologies. Of particular interest is ASIC3, which recognised as key sensor acid-induced pain and important the establishment arising from inflammatory conditions, such rheumatoid arthritis. Thus, identification new ASIC3 modulators mechanistic understanding how these compounds modulate could be for development strategies to counteract...
We have previously shown that metalloproteinase 7 (MMP7) expression is increased during the acquisition of resistance to oxaliplatin in colon cancer cells. Now we analyzed implication β-catenin and EGFR pathways up-regulation MMP7 oxaliplatin-resistant human cell lines RHT29 RHCT116 p53-/-, derived from HT29 HCT116 p53-/- cells, respectively.Oxaliplatin treatment induced its activation all lines. However, mRNA was only upregulated with a marked increase nuclear/cytoplasmic protein ratio To...
Acid sensing in the gastrointestinal tract is required for gut homeostasis and detection of tissue acidosis caused by ischaemia, inflammation infection. In colorectum, activation colonic afferents low pH contributes to visceral hypersensitivity abdominal pain human disease including during inflammatory bowel disease. The naked mole-rat ( Heterocephalus glaber) shows no pain-related behaviour subcutaneous acid injection cutaneous are insensitive acid, an adaptation thought be a consequence...