A5050378272- Pain Mechanisms and Treatments
- Trigeminal Neuralgia and Treatments
- Ion channel regulation and function
- Neurotransmitter Receptor Influence on Behavior
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Neuroscience of respiration and sleep
- Migraine and Headache Studies
- Botulinum Toxin and Related Neurological Disorders
- Anesthesia and Pain Management
- Stress Responses and Cortisol
- Cancer, Stress, Anesthesia, and Immune Response
- Pain Management and Placebo Effect
- Neurological disorders and treatments
- Biochemical effects in animals
- Pediatric Pain Management Techniques
- X-ray Diffraction in Crystallography
- Nicotinic Acetylcholine Receptors Study
- Venomous Animal Envenomation and Studies
- Pesticide Exposure and Toxicity
- Pregnancy and Medication Impact
- Pharmacological Effects and Toxicity Studies
- Coordination Chemistry and Organometallics
- Cholinesterase and Neurodegenerative Diseases
- Pancreatic function and diabetes
University of Calgary
2019-2025
Alberta Children's Hospital
2019-2025
Universidade Federal do Paraná
2015-2019
The medial prefrontal cortex (mPFC) is a brain region involved in the affective components of pain and undergoes plasticity during development chronic pain. Dopamine (DA) key neuromodulator mesocortical circuit modulates working memory aversion. Although DA inputs into mPFC are known to modulate plasticity, whether how these affect remains incompletely understood. By using optogenetics, we find that phasic activation from ventral tegmental area (VTA) reduce mechanical hypersensitivity...
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...
Trigeminal neuralgia (TN) is a rare but debilitating disorder characterized by excruciating facial pain, with higher incidence in women. Recent studies demonstrated that TN patients present mutations the gene encoding Ca V 3.2 T-type calcium channel, an important player peripheral pain pathways. We characterize role of channels at 2 levels. First, we examined biophysical properties CACNA1H variants found patients. Second, investigated animal model trigeminal neuropathic pain. Whole-cell...
Chlorpyrifos is a pesticide, member of the organophosphate class, widely used in several countries to manage insect pests on many agricultural crops. Currently, chlorpyrifos health risks are being reevaluated due possible adverse effects, especially central nervous system. The aim this study was investigate action pesticide behaviors related anxiety and depression offspring rats exposed during pregnancy. Wistar were treated orally with (0.01, 0.1, 1 10mg/kg/day) gestational days 14-20. Male...
Neuropathic pain is a debilitating condition that often refractory to treatment. The network of neural substrates for transmission and control within the brain complex remains poorly understood. Through combination neuronal tracing, optogenetics, chemogenetics, electrophysiological recordings, behavioral assessment, we demonstrate activation layer 5 pyramidal neurons in ventrolateral orbitofrontal cortex (vlOFC) attenuates mechanical thermal hypersensitivity cold allodynia mice with...
Cav3.2 calcium channels are important mediators of nociceptive signaling in the primary afferent pain pathway, and their expression is increased various rodent models chronic pain. Previous work from our laboratory has shown that this part mediated by an aberrant deubiquitinase USP5, which associates with these increases stability. Here, we report on a novel bioactive rhodanine compound (II-1), was identified library screens. II-1 inhibits biochemical interactions between USP5 domain III-IV...
The insula and anterior cingulate cortex (ACC) are brain regions that undergo structural functional reorganization in neuropathic pain states. Here, we aimed to study inhibitory parvalbumin positive (PV+) posterior (pIC) ACC (pACC) projections, evaluate the effects of direct optogenetic manipulation such projections on mechanical nociception spontaneous ongoing mice with Spared Nerve Injury (SNI). CTB488 tract-tracing male PVCrexAi9 revealed a small proportion PV+ from pIC pACC....
A novel missense mutation in the CACNA1A gene that encodes pore forming α1 subunit of CaV2.1 voltage-gated calcium channel was identified a patient with trigeminal neuralgia. This leads to substitution proline 2455 by histidine (P2455H) distal C-terminus region channel. Due well characterized role this neurotransmitter release, our aim characterize biophysical properties P2455H variant heterologously expressed channels. Whole-cell patch clamp recordings wild type and mutant channels tsA-201...
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...
(Cell Reports 31, 107812-1–107812-9.e1–e6; June 23, 2020) In the originally published version of this article, bars in Figures 2D and 2E were incorrectly superimposed on individual data points that reflect experimental measurements. have now been corrected online appear below. Figure S3C, green red accidentally swapped between two conditions. other words, shown bar should vice versa. S3C has appears None statistical analysis or interpretations findings affected by oversight. The authors...
Abstract Trigeminal neuralgia (TN) is a rare form of chronic neuropathic pain characterized by spontaneous or elicited paroxysms electric shock-like stabbing in region the face. While most cases occur sporadic manner and are accompanied intracranial vascular compression trigeminal nerve root, alteration ion channels has emerged as potential exacerbating factor. Recently, whole exome sequencing analysis familial TN patients identified 19 variants gene CACNA1H encoding for Ca v 3.2T-type...
More than 80% of patients may experience acute pain after a surgical procedure, and this is often refractory to pharmacological intervention. The identification new targets treat postoperative necessary. There an association polymorphisms in the Ca
It is known that diabetic (DBT) animals present dysregulation on the serotonergic system in several brain areas associated with anxiety-like responses. The aim of this study was to investigate involvement 5-HT 1A receptors dorsal periaqueductal gray (dPAG) behavioral response related panic disorder type-1 DBT animals. For this, escape by electric stimulation (ES) dPAG and normoglycemic (NGL) assessed. Both NGL were exposed an open-field test (OFT) 28 days after confirmation. current...