A5000541661- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Connexins and lens biology
- Biochemical effects in animals
- Cannabis and Cannabinoid Research
- Nicotinic Acetylcholine Receptors Study
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Ion Channels and Receptors
- Retinoids in leukemia and cellular processes
- Adenosine and Purinergic Signaling
- Heme Oxygenase-1 and Carbon Monoxide
- Zebrafish Biomedical Research Applications
- Peripheral Neuropathies and Disorders
- Pain Management and Placebo Effect
- Anesthesia and Pain Management
- Neuroscience of respiration and sleep
- Hemispheric Asymmetry in Neuroscience
- Musculoskeletal pain and rehabilitation
- Memory and Neural Mechanisms
- Neurobiology and Insect Physiology Research
- Cephalopods and Marine Biology
Alberta Children's Hospital
2022-2025
University of Calgary
2020-2025
University of Toronto
2020-2024
Hospital for Sick Children
2014-2021
SickKids Foundation
2017
Background and Purpose Cannabinoids are a promising therapeutic avenue for chronic pain. However, clinical trials often fail to report analgesic efficacy of cannabinoids. Inhibition voltage gate calcium (Ca v ) channels is one mechanism through which cannabinoids may produce analgesia. We hypothesized that cannabinoid receptor agonists target different types Ca distinct mechanisms. Experimental Approach Electrophysiological recordings from tsA‐201 cells expressing either 3.2 or 2.2 were used...
The composition of the postsynaptic ionotropic receptors that receive presynaptically released transmitter is critical not only for transducing and integrating electrical signals but also coordinating downstream biochemical signaling pathways. At glutamatergic synapses in adult CNS an overwhelming body evidence indicates NMDA receptor (NMDAR) component synaptic responses dominated by NMDARs containing GluN2A subunit, while GluN2B, GluN2C, or GluN2D play minor roles transmission. Here, we...
Cav3.2 T-type calcium channels and their dysregulation by the deubiquitinase USP5 contribute to development of inflammatory neuropathic pain. We report on a pediatric patient with de novo heterozygous missense mutation R24W in who exhibits pain insensitivity. created CRISPR knock-in mouse harboring this performed detailed behavioral analyses acute chronic models. Heterozygous mice both sexes are resistant thermal hypersensitivity In contrast, only male confer resistance mechanical...
T-type voltage-gated calcium channels are an emerging therapeutic target for neurological disorders including epilepsy and pain. Inhibition of reduces the excitability peripheral nociceptive sensory neurons reverses pain hypersensitivity in male rodent models. However, administration peripherally restricted antagonists failed to show efficacy multiple clinical preclinical trials, suggesting that inhibition alone may be insufficient relief.We utilized selective CNS-penetrant channel...
N- and P/Q-type voltage-gated Ca
The ventrolateral periaqueductal gray (vlPAG) functionally projects to diverse brain regions, including the locus coeruleus (LC). Excitatory projections from vlPAG LC are well described, while few studies have indicated possibility of inhibitory projections. Here, we quantified relative proportion excitatory and vlPAG-LC in male female mice, found an unexpected overlapping population neurons expressing both GAD2 VGLUT2. Combined
Abstract Opioid withdrawal is a liability of chronic opioid use and misuse, impacting people who prescription or illicit opioids. Hyperactive autonomic output underlies many the aversive symptoms that make it difficult to discontinue use. The locus coeruleus (LC) an important centre within brain with poorly defined role in withdrawal. We show here pannexin-1 (Panx1) channels expressed on microglia critically modulate LC activity during Within LC, we found spinally projecting tyrosine...
Maladaptive plasticity of neurons in lamina I the spinal cord is a lynchpin for development chronic pain, and critically dependent on intracellular calcium signaling. However, relationship between neuronal activity these unknown. Here we combined two-photon imaging with whole-cell electrophysiology to determine how action potential firing drives responses within subcellular compartments male rat neurons. We found that single potentials generated at soma increase concentration somatic cytosol...
Abstract Drug dependence is characterized by a switch in motivation wherein positively reinforcing substance can become negatively reinforcing. Put differently, drug use transform from form of pleasure‐seeking to relief‐seeking. Ventral tegmental area (VTA) GABA neurons an anatomical point divergence between two double dissociable pathways that have been shown be functionally implicated and necessary for these respective motivations seek drugs. The pedunculopontine nucleus (TPP) opiate...
Abstract Drug dependence is characterized by a switch in motivation wherein positively reinforcing substance becomes negatively reinforcing. Ventral tegmental area (VTA) GABA neurons form point of divergence between two double dissociable pathways responsible for these respective motivational states. Here we show that this from drug-naïve to opiate-dependent and withdrawn (ODW) contingent upon the gap junction-forming protein, connexin-36 (Cx36), VTA neurons. Intra-VTA infusions Cx36...