A5033977436- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Botulinum Toxin and Related Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neurobiology and Insect Physiology Research
- Neuroscience and Neural Engineering
- Memory and Neural Mechanisms
- Anesthesia and Neurotoxicity Research
- Stroke Rehabilitation and Recovery
- Ion Channels and Receptors
- Transcranial Magnetic Stimulation Studies
- Mitochondrial Function and Pathology
- Nicotinic Acetylcholine Receptors Study
- Spinal Cord Injury Research
- Acupuncture Treatment Research Studies
- Neurological Disease Mechanisms and Treatments
- Sleep and Wakefulness Research
- Pluripotent Stem Cells Research
- Pediatric Pain Management Techniques
- Nerve Injury and Rehabilitation
- Genomics and Rare Diseases
- Neuropeptides and Animal Physiology
Bogomoletz Institute of Physiology
2015-2024
University College London
2022-2024
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) are ligand-gated cationic channels formed from combinations of GluA1-4 subunits. Pathogenic variants GRIA1-4 have been described in patients with developmental delay, intellectual disability, autism spectrum disorder, and seizures, GRIA2 typically causing AMPAR loss function. Here, we identify a novel, heterozygous de novo pathogenic missense mutation (c.1928 C>T, p.A643V, NM_001083619.1) 1-year-old boy...
Persistent peripheral inflammation alters trafficking of AMPA receptors (AMPARs) at the synapses between primary afferents and dorsal horn (DH) neurons that contribute to maintenance inflammatory pain. However, whether changes synaptic activity within DH circuitry how it modulates AMPARs in different neuronal types still remain unknown. We find complete Freund adjuvant (CFA)-induced prominently augments excitatory neurotransmission rat lamina II characterized by intrinsic adapting firing...
Upregulation of Ca(2+)-permeable AMPA receptors (CP-AMPARs) in the dorsal horn (DH) neurons spinal cord has been causally linked to maintenance persistent inflammatory pain. Therefore, inhibition CP-AMPARs could potentially alleviate an, otherwise, poorly treatable chronic However, a loss produce considerable side effects because crucial role synaptic plasticity. Here we have tested whether with dicationic compounds, open-channel antagonists acting an activity-dependent manner, can relieve...
Abstract Lamina I spino-parabrachial neurons (SPNs) receive peripheral nociceptive input, process it and transmit to the supraspinal centres. Although responses of SPNs cutaneous receptive field stimulations have been intensively studied, mechanisms signal processing in these are poorly understood. Therefore, we used an ex-vivo spinal cord preparation examine synaptic cellular determining specific input-output characteristics neurons. The vast majority received a few direct C-fiber inputs...
Spasticity, a common complication after spinal cord injury (SCI), is frequently accompanied by chronic pain. The physiological origin of this pain (critical to its treatment) remains unknown, although spastic motor dysfunction has been related the hyperexcitability motoneurons and changes in sensory processing. Here we show that mechanism involves circuits dorsal horn (DH) where nociceptive inputs integrate for Spasticity associated with DH resulting from an increase excitation disinhibition...
Functional properties of lamina X neurons in the spinal cord remain unknown despite established role this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations neuronal functioning have been hampered by technical challenges. Here we introduce an ex-vivo preparation with both dorsal ventral roots still attached functional studies their connectivity using oblique LED illumination resolved visualization a thick tissue....
Although spinal processing of sensory information greatly relies on afferent-driven (AD) presynaptic inhibition (PI), our knowledge about how it shapes peripheral input to different types nociceptive neurons remains insufficient. Here we examined the AD-PI primary afferent in marginal layer, lamina I, and layer surrounding central canal, X; two nociceptive-processing regions with similar patterns direct supply by Aδ- C-afferents. Unmyelinated C-fibers were selectively activated electrical...
The hippocampus is the region of brain that most susceptible to ischemic lesion because it contains pyramidal neurons are highly vulnerable cell death. A restricted neurogenesis limits possibility reversing massive death after stroke and, hence, endorses cell-based therapies for neuronal replacement strategies following cerebral ischemia. Neurons differentiated from neural stem/progenitor cells (NSPCs) can mature and integrate into host circuitry, improving recovery stroke. However, how...
The spinal gray matter region around the central canal, lamina X, is critically involved in somatosensory processing and visceral nociception. Although several classes of primary afferent fibers terminate or decussate this area, little known about organization functional significance supply X neurons. Using hemisected ex vivo cord preparation, we show that virtually all neurons receive inputs, which are predominantly mediated by high-threshold Aδ- C-fibers. In two-thirds tested, inputs were...
Measuring signal propagation through nerves is a classical electrophysiological technique established decades ago to evaluate sensory and motor functions in the nervous system. The whole-nerve preparation provides valuable model investigate nerve function ex vivo; however, it requires specific knowledge ensure successful stable measurements. Although methodology for sciatic recordings has long existed, method reliable long-lasting from myelinated non-myelinated (nociceptive) fibers still...
Second-order spinal cord excitatory neurons play a key role in processing and transmission of pain signals to the brain. Exogenously induced change developmentally imprinted neurotransmitter phenotypes these inhibitory has not yet been achieved. Here, we use subpial dorsal horn-targeted delivery AAV (adeno-associated virus) vector(s) encoding GABA (gamma-aminobutyric acid) synthesizing-releasing machinery mice with neuropathic pain. Treated animals showed progressive complete reversal...
Upregulation of Ca2+-permeable AMPA receptors (CP-AMPARs) in dorsal horn (DH) neurons has been causally linked to persistent inflammatory pain. This upregulation, demonstrated for both synaptic and extrasynaptic AMPARs, depends on the protein kinase C alpha (PKCα) activation; hence, spinal PKC inhibition alleviated peripheral nociceptive hypersensitivity. However, whether targeting PKCα would alleviate pain development maintenance not explored yet (essential pharmacological translation)....
Abstract Despite being involved in a number of functions, such as nociception and locomotion, spinal lamina X remains one the least studied central nervous system regions. Here, we show that Aδ- C-afferent inputs to neurons are presynaptically inhibited by homo- heterosegmental afferents well descending fibers from corticospinal tract, dorsolateral funiculus, anterior funiculus. Activation tracts suppresses primary afferent-evoked action potentials also elicits excitatory (mono-...
Among all the brain, hippocampus is most susceptible region to ischemic lesion, with highest vulnerability of CA1 pyramidal neurons damage. This damage may cause either prompt neuronal death (within hours) or a delayed appearance (over days), providing window for applying potential therapies reduce prevent impairments. However, time course when turns strictly depends on experimental modelling cerebral ischemia and, up now, studies were predominantly focused short time-window ¬– from hours...
• Spared nerve injury (SNI) altered the action potential (AP) output of lamina I spino-parabrachial neurons (SPNs) without affecting their resting or membrane resistance. In one-third SPNs, high-threshold dorsal root stimulation elicited persistent AP firing which was never observed in cells from naïve animals. 38% SPNs SNI rats showed spontaneous firing. After low- and high-output were no longer nociceptive-specific as part them responded with APs to low-threshold stimulation. These...
Motor disability is a common outcome of spinal cord injury (SCI). The recovery motor function after depends on the severity neurotrauma; deficit can be reversible, at least partially, due to innate tissue capability recover, which, however, deteriorates with age. Pain often comorbidity injury, although its prediction remains poor. It largely unknown whether pain attend dysfunction. Here, we implemented SCI for modelling severe and moderate neurotrauma monitored rats up 5 months post-injury...
Despite playing diverse physiological roles, the area surrounding central canal, lamina X, remains one of least studied spinal cord regions. Technical challenges and limitations commonly used experimental approaches are main difficulties that hamper X research. In current protocol, we describe a reliable method for functional investigation neurons requires neither time-consuming slicing nor sophisticated in vivo experiments. Our approach relies on ex hemisected preparation preserves...
В статье сделан обзор литературы по такой проблеме, как боль в спине (дорсалгия). Представлены источники дорсалгии, актуальность проблемы, история вопроса, терминология, некоторые аспекты патогенеза, Международная классификация болезней 10-го пересмотра, три типа Модик-изменений тел позвонков при магнитно-резонансной томографии у пациентов с грыжей межпозвоночного диска, причины спонтанного регресса грыжи диагностика заболеваний болью спине, критерии неспецифической (скелетно-мышечной) боли,...
Abstract AMPA-type glutamate receptors (AMPARs) are tetrameric ligand-gated ion channels formed as different combinations of GluA1-4 subunits encoded by the genes GRIA1-4 . Various pathogenic variants these have been described in patients with developmental delay, intellectual disability, autistic spectrum disorder and seizures. Here we report a heterozygous de novo missense mutation GRIA2 (c.1928 C>T, p.A643V) identified one-year-old male patient seizures, delay failure to thrive....