A5032909017- Pain Mechanisms and Treatments
- Ion channel regulation and function
- Ion Channels and Receptors
- Neuropeptides and Animal Physiology
- Human-Automation Interaction and Safety
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Cancer, Stress, Anesthesia, and Immune Response
- Nerve injury and regeneration
- Pharmacological Effects of Natural Compounds
- Software Engineering Techniques and Practices
- Exercise and Physiological Responses
- Occupational Health and Safety Research
- Neuroendocrine regulation and behavior
- Fault Detection and Control Systems
- Human Resource Development and Performance Evaluation
- Cardiac electrophysiology and arrhythmias
- Veterinary Pharmacology and Anesthesia
- Autism Spectrum Disorder Research
- Cancer-related cognitive impairment studies
- Cellular transport and secretion
- Mindfulness and Compassion Interventions
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Software Engineering Methodologies
The University of Texas MD Anderson Cancer Center
2019-2025
Washington University in St. Louis
2015-2024
GlaxoSmithKline (United Kingdom)
2024
University of Missouri–St. Louis
2023
University of Iowa
2010-2022
Stanford University
2022
University of Manchester
2005-2019
Institute of Pharmacology
2012
Virginia Commonwealth University
2010
Loughborough University
1985-2005
Significance Neuropathic pain is a widespread problem that undermanaged by currently available analgesic drugs. An antagonist of the type II angiotensin receptor (AT2R) reduces behaviors related to neuropathy, suggesting signaling involved in this pain. We find AT2R expression detected not sensory neurons themselves, but macrophages infiltrate site nerve injury. Inducible depletion peripheral attenuates mechanical and cold hypersensitivity as does transplantation AT2R-null bone marrow into...
Abstract Neurodegenerative disorders, including chemotherapy-induced cognitive impairment, are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces dysfunction in vivo and vitro. Astrocytes key players supporting development, synaptogenesis, axonal growth, metabolism and, potentially health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment restore an vitro system which containing...
Injury, inflammation, and nerve damage initiate a wide variety of cellular molecular processes that culminate in hyperexcitation sensory nerves, which underlies chronic inflammatory neuropathic pain. Using behavioral readouts pain hypersensitivity induced by angiotensin II (Ang II) injection into mouse hindpaws, our study shows activation the type 2 Ang receptor (AT2R) cell-damage-sensing ion channel TRPA1 are required for peripheral mechanical sensitization male female mice. However, we...
Parasympathetic regulation of heart rate is mediated by acetylcholine binding to G protein-coupled muscarinic M2 receptors, which activate heterotrimeric G(i/o) proteins promote inwardly rectifying K(+) (GIRK) channel activation. Regulator protein signaling (RGS) proteins, function inactivate are indispensable for normal parasympathetic control the heart. However, it unclear more than 20 known RGS negatively regulate and thereby ensure heart.To examine specific contribution RGS6 as an...
The complement cascade is a principal component of innate immunity. Recent studies have underscored the importance C5a and other components system in inflammatory neuropathic pain, although underlying mechanisms are largely unknown. In particular, it unclear how communicates with nociceptors which ion channels receptors involved. Here we demonstrate that thermal mechanical hyperalgesia induced by complete Freund's adjuvant was accompanied upregulation markedly reduced receptor (C5aR1)...
It has been suggested that the lack of rodent behavioral assays represent complexities human pain contributes to poor translational record basic research findings. Clinically, chronic interferes with patient mobility and physical/social activities, increases anxiety symptoms, in turn negatively impacting quality life. To determine whether these behaviors are similarly influenced by putative manipulations rodents, we systematically evaluated wheel running, locomotion, gait, social...
In inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, resolution due their phenotypic plasticity in response signals from microenvironments. infiltrate polarize toward pro-inflammatory phenotype (M1-like), thereby increasing severity inflammation. Therefore, we aimed suppress activity M1-like macrophages decrease infiltration at site insult resolve...
γ-Aminobutyric acid (GABA) release from inhibitory interneurons located within the cerebellar cortex limits extent of neuronal excitation in part through activation metabotropic GABA(B) receptors. Stimulation these receptors triggers a number downstream signaling events, including GIRK channels by Gβγ dimer resulting membrane hyperpolarization and inhibition neurotransmitter presynaptic sites. Here, we identify RGS6, member R7 subfamily RGS proteins, as key regulator GABA(B)R cerebellum....
Abstract The complement system significantly contributes to the development of inflammatory and neuropathic pain, but underlying mechanisms are poorly understood. Recently, we identified signaling pathway responsible for thermal hypersensitivity induced by component C5a. Here, examine another important action C5a, induction mechanical hypersensitivity. We found that intraplantar injection C5a produced a dose-dependent sensitization this effect was blocked chemogenetic ablation macrophages in...
Natriuretic peptides (NPs) control natriuresis and normalize changes in blood pressure. Recent studies suggest that NPs are also involved the regulation of pain sensitivity, although underlying mechanisms remain essentially unknown. Many biological effects mediated by guanylate cyclase (GC)-coupled NP receptors, NPR-A NPR-B, whereas third receptor, NPR-C, lacks GC kinase domain acts as clearance receptor. In addition, NPR-C can couple to specific Gα i –Gβγ-mediated intracellular signaling...
The chemokine stromal cell-derived factor-1α (SDF-1α) has multiple effects on neuronal activity, survival, and death under conditions that generate a proinflammatory microenvironment within the brain, via signaling through C-X-C-type receptor 4 (CXCR4), although underlying cellular/molecular mechanisms are unclear. Using rat hippocampal neurons, we investigated distinct modifications in voltage-gated K + (Kv) channel Kv2.1 response to short- long-term SDF-1α/CXCR4-mediated as an mechanism...
Burrowing, or the removal of material from an enclosed tube, is emerging as a prominent means testing changes in voluntary behavior rodent models various pain states. Here, we report no significant differences between male and female mice terms burrowing performance, substantially shorter time frame than previous reports. We found that color burrow tube affects variability performance when tested lit room, suggesting light aversion at least partial driver this behavior. Spared nerve injury...
Abstract Complications associated with Type 1 and 2 diabetes, such as diabetic peripheral neuropathy foot ulcers, are a growing health-care concern. In addition, this concern increases patients age due to their increased susceptibility complications. To address problem, it is important understand fluctuations in physiology which lead pathological changes the metabolic disturbances of diabetes. Our study explores dysregulation immune cell populations hindpaws healthy mice at 12 21 weeks using...
Abstract The technique of hierarchical task analysis (HTA), proposed by Annett et al. (1971), which requires the analyst to describe a in terms hierarchy operations and plans, is reviewed examined as basis for making training decisions. basic ideas originally stated are main accepted, with some qualifications. benefit neutrally emphasized means establishing agreement between sponsor work, before more speculative human factor decisions undertaken. necessity plans statements conditions under...