A5079451694- Pain Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Multiple Sclerosis Research Studies
- Neuropeptides and Animal Physiology
- Peripheral Neuropathies and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Exercise and Physiological Responses
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Stress Responses and Cortisol
- Circular RNAs in diseases
- Ion channel regulation and function
- Endoplasmic Reticulum Stress and Disease
- MicroRNA in disease regulation
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- Spinal Cord Injury Research
- Neurogenetic and Muscular Disorders Research
- Pharmacological Receptor Mechanisms and Effects
- Axon Guidance and Neuronal Signaling
- Anesthesia and Pain Management
- Vagus Nerve Stimulation Research
- Vestibular and auditory disorders
- Cytokine Signaling Pathways and Interactions
University of Alberta
2016-2025
Women and Children’s Health Research Institute
2015-2025
MacEwan University
2022
United States Department of Agriculture
2021
Agricultural Research Service
2021
Pain and Rehabilitation Medicine
2018
University of Montana
2014
McGill University Health Centre
2007-2011
McGill University
1996-2008
California Institute of Technology
2004-2005
Central sensitization, the hyperexcitability of spinal processing that often accompanies peripheral injury, is a major component many persistent pain states. Here we report neurotrophin, brain-derived neurotrophic factor (BDNF), modulator excitability within cord and contributes to mechanism central sensitization. BDNF, localized in primary sensory neuron cell bodies terminals, potentiates nociceptive reflex responses an vitro preparation induces c-fos expression dorsal horn neurons. NMDA...
IL-1β and TNF are potential targets in the management of neuropathic pain after injury. However, importance IL-1 systems for peripheral nerve regeneration mechanisms by which these cytokines mediate effects to be fully elucidated. Here, we demonstrate that mRNA protein levels rapidly upregulated injured mouse sciatic nerve. Mice lacking both TNF, or type 1 receptor (IL-1R1) (TNFR1), showed reduced nociceptive sensitivity (mechanical allodynia) compared with wild-type littermates...
Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response injury; however, similarities between these cells make it challenging distinguish their relative contributions. We genetically labeled microglia CNS-associated them from macrophages. Using single-cell RNA sequencing, we describe multiple activation states, one of which was enriched for interferon associated signaling. Although blood-derived acutely infiltrated demyelinated lesion,...
The tetrodotoxin-resistant voltage-gated sodium channel Nav 1.8 is expressed only in nociceptive sensory neurons. This has been proposed to contribute significantly the sensitization of primary neurons after injury. We have studied behaviours mice carrying a null mutation gene (Nav -/-) models peripheral inflammation as well model neuropathic pain. results from present studies reveal that necessary mediator NGF-induced thermal hyperalgesia but not essential for PGE2-evoked hypersensitivity....
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While primary symptoms MS are losses sensory and motor functions, it now recognized that chronic pain also a major concern affecting between 50% 80% patients. To date, however, few studies have examined underlying mechanisms in or animal model, experimental autoimmune encephalomyelitis (EAE), which shares many features pathology. We, therefore, set out to characterize changes sensitivity...
Chronic neuropathic pain is a common symptom of multiple sclerosis (MS). MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) has been used as an animal model to investigate the mechanisms in MS. Previous studies have implicated sensitization spinal nociceptive networks pathogenesis EAE. However, involvement supraspinal sites integration, such primary somatosensory cortex (S1), not defined. We therefore examined functional, structural, and immunological alterations S1 during...
Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system (CNS). It widely accepted that cells play major roles in pathogenesis MS, possibly through use serine protease granzyme B (GrB) secreted from granules cytotoxic T cells. We have previously identified GrB as a mediator axonal injury neuronal death. In this study, our goal was to evaluate effect inhibition human vitro, vivo EAE using newly isolated GrB-inhibitor serpina3n. used...
Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has manifestations that range from impaired clearance unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between the triggering protein response (UPR) downstream dysfunction are poorly understood, membranous contacts ER mitochondria, called mitochondria-associated membrane (MAM), could provide functional link...
Research Article9 October 2017Open Access Source DataTransparent process Disease-modifying effects of ganglioside GM1 in Huntington's disease models Melanie Alpaugh Department Pharmacology, University Alberta, Edmonton, AB, Canada Neuroscience and Mental Health Institute, Search for more papers by this author Danny Galleguillos Juan Forero Faculty Rehabilitation Medicine, Luis Carlos Morales Sebastian W Lackey Preeti Kar Alba Di Pardo Andrew Holt Bradley J Kerr Anesthesiology Pain Kathryn G...
Abstract The neuropeptide galanin has been identified as a potential neurotransmitter/neuromodulator within the central nervous system. In present study, role of endogenous in nociceptive processing system analysed by using mice carrying targeted mutation gene. Supporting this, effect chronic administration exogenous on sensory inputs assayed adult rats. absence peripheral nerve injury, sensitivity to threshold noxious stimuli is significantly higher mutant than wild‐type controls. Following...
CNS injury-induced hemorrhage and tissue damage leads to excess iron, which can cause secondary degeneration. The mechanisms that handle this iron are not fully understood. We report spinal cord contusion injury (SCI) in mice induces an “iron homeostatic response” partially limits iron-catalyzed oxidative damage. show ceruloplasmin (Cp), a ferroxidase oxidizes toxic ferrous is important for process. SCI Cp-deficient demonstrates Cp detoxifies mobilizes reduces degeneration functional loss....
Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss. While therapies exist to slow MS progression, no treatment currently exists for remyelination. Remyelination, linked reduced disability in MS, relies on microglia and monocyte-derived macrophages (MDMs). This study aims understand the role of during remyelination lineage tracing depleting them. Microglial reveals that both MDMs initially accumulate, but later dominate lesion. Microglia engulf equal amounts...