A5007034989- Pain Mechanisms and Treatments
- Neuroscience of respiration and sleep
- Pediatric Pain Management Techniques
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Sleep and Wakefulness Research
- Zebrafish Biomedical Research Applications
- Ion Channels and Receptors
- Pain Management and Placebo Effect
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cannabis and Cannabinoid Research
- Adenosine and Purinergic Signaling
- Biochemical effects in animals
- Botulinum Toxin and Related Neurological Disorders
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Anesthesia and Pain Management
- Neural dynamics and brain function
- Prenatal Substance Exposure Effects
- Memory and Neural Mechanisms
- Herbal Medicine Research Studies
- Neurotransmitter Receptor Influence on Behavior
- Photoreceptor and optogenetics research
- Pharmacological Receptor Mechanisms and Effects
- Psychosomatic Disorders and Their Treatments
University of Calgary
2017-2024
Université Toulouse III - Paul Sabatier
2020
Université de Toulouse
2020
Allen Institute for Brain Science
2019
University College London
2015-2018
University of Nottingham
2013-2017
Queen's Medical Centre
2015
King's College London
2010
Microglia-neuron signalling in the spinal cord is a key mediator of mechanical allodynia caused by peripheral nerve injury. We recently reported sex differences microglia pain mice: mechanisms underlying injury-induced are microglial dependent male but not female mice. Whether this difference hypersensitivity conserved other species unknown. Here, we show that rats, males differ from those females, with P2X4 receptors (P2X4Rs) being point divergence. In injury produced comparable and...
A new therapeutic option for treating arthritis pain.
Abstract Dopamine is well known to regulate movement through the differential control of direct and indirect pathways in striatum that express D 1 2 receptors respectively. The spinal cord also expresses all dopamine receptors; however, how specific network output mammals poorly understood. We explore receptor-specific mechanisms underlie dopaminergic neonatal mice during changes excitability. During spontaneous activity, which a characteristic developing networks operating low excitability...
Significant opioid-dependent changes occur during the fourth postnatal week in supraspinal sites (rostroventral medulla [RVM], periaqueductal grey [PAG]) that are involved descending control of spinal excitability via dorsal horn (DH). Here we report developmentally regulated opioidergic signalling within PAG and DH, which further increase our understanding pain processing early life. Microinjection μ-opioid receptor (MOR) agonist DAMGO (30 ng) into Sprague-Dawley rats increased lowered...
Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity restricted to nociceptive pathways. Here, we investigate the effect repeated neonatal noxious or innocuous hind paw adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats both sexes received 4 unilateral left needle pricks (NPs, n = 13) tactile (cotton swab touch) stimuli, per day...
Limbic brain regions drive goal-directed behaviors. These behaviors often require dynamic motor responses, but the functional connectome of limbic structures in diencephalon that control locomotion is not well known. The A11 region, within posterior has been postulated to contribute function and pain. Here we show region initiates movement. Photostimulation channelrhodopsin 2 (ChR2) transfected neurons slice preparations showed could follow stimulation at frequencies 20 Hz. Our data...
The recent identification of novel cellular substrates opioid withdrawal that are blocked by clinically approved drugs brings the promise much needed new therapies.
In Brief The rostroventral medial medulla (RVM) is part of a rapidly acting spino-bulbo-spinal loop that activated by ascending nociceptive inputs and drives descending feedback modulation spinal nociception. the adult rat, RVM can facilitate or inhibit dorsal horn neuron but in young animals facilitation dominates. It not known whether this early life loop. We hypothesized newborn functions independently sensory input, before maturation control. show here noxious hind paw pinch evokes no...
Pain is the most debilitating symptom in juvenile idiopathic arthritis. As pain correlates poorly to extent of joint pathology, therapies that control inflammation are often inadequate as analgesics. We test hypothesis leads sensitisation nociceptive circuits central nervous system, which maintained by cytokine expression spinal cord. Here, transient was induced postnatal day (P)21 and P40 male Sprague-Dawley rats with a single intra-articular ankle injection complete Freund's adjuvant....
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...
Increased afferent input resulting from painful injury augments the activity of central nociceptive circuits via both neuron-neuron and neuron-glia interactions. Microglia, resident immune cells nervous system (CNS), play a crucial role in pathogenesis chronic pain. This study provides framework for understanding how peripheral joint signals CNS to engage spinal microglial responses. During first week monosodium iodoacetate (MIA)-induced knee male rats, inflammatory neuropathic pain were...
Postoperative shivering and cold hypersensitivity are major side effects of acute chronic opioid treatments respectively. TRPM8 is a menthol-sensitive channel found in subset dorsal root ganglion (DRG) nociceptors. Deletion or inhibition the was to prevent hyperalgesia induced by administration morphine. Here, we examined mechanisms which morphine able promote DRG neurons transfected HEK cells. Mice daily injected with for 5 days developed hyperalgesia. Treatment did not alter expressions...
Pain hypersensitivity resulting from peripheral nerve injury depends on pathological microglial activation in the dorsal horn of spinal cord. This activity is critically modulated by P2X7 receptors (P2X7R) and ATP stimulation these produces mechanical allodynia, a defining feature neuropathic pain. Peripheral increases P2X7R expression potentiates its cation channel function microglia. Here, we report means to preferentially block potentiation delivering membrane permeant small interfering...
Abstract Significant age- and experience-dependent remodelling of spinal supraspinal neural networks occur, resulting in altered pain responses early life. In adults, endogenous opioid peptide endocannabinoid (ECs) control systems exist which modify responses, but the role they play acute to postnatal neurodevelopment is unknown. Here, we have studied changing ECs brainstem nuclei essential for nociception from birth adulthood both rats humans. Using vivo electrophysiology, show that...
Abstract The rostral ventromedial medulla ( RVM ) regulates a range of involuntary behaviours but is most often associated with nociception via the action pronociceptive ON cells and antinociceptive OFF cells. phasic responses determine whether or not incoming noxious signals provoke withdrawal reflex, previous studies have suggested that reflex activity patterns actively shape motor output. Here we challenged model by using juvenile rats, which are known to exhibit markedly different...
Abstract Spinal cord injury and peripheral nerve injuries are traumatic events that greatly impact quality of life. One factor is being explored throughout patient care the idea diet role it has on outcomes. But effects following neurotrauma need to be carefully in animal models ensure they have beneficial effects. The ketogenic provides sufficient daily caloric requirements while potentially neuroprotective analgesic. In this study, animals were fed a high-fat, low-carbohydrate led high...