A5009284894- Pain Mechanisms and Treatments
- Neurobiology and Insect Physiology Research
- Dermatology and Skin Diseases
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Ion Channels and Receptors
- Ion channel regulation and function
- Musculoskeletal pain and rehabilitation
- Neuroendocrine regulation and behavior
- Neuroscience and Neural Engineering
- Transcranial Magnetic Stimulation Studies
- Myofascial pain diagnosis and treatment
- Neural dynamics and brain function
- Mindfulness and Compassion Interventions
- Axon Guidance and Neuronal Signaling
- Spine and Intervertebral Disc Pathology
- Stress Responses and Cortisol
- Botulinum Toxin and Related Neurological Disorders
- Advancements in Transdermal Drug Delivery
- Sleep and Wakefulness Research
- Neuroscience of respiration and sleep
- Hormonal and reproductive studies
- Neurogenesis and neuroplasticity mechanisms
- Sympathectomy and Hyperhidrosis Treatments
- Pediatric Pain Management Techniques
University of Glasgow
2015-2025
Hunter Medical Research Institute
2020
University of Newcastle Australia
2020
University of Edinburgh
2014-2017
Faculty of Public Health
2009
Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate passage information conveyed low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate polysynaptic relay LTMR input to inhibiting lamina II excitatory whose axons project into I. We changes...
Abstract Excitatory interneurons account for the majority of neurons in superficial dorsal horn, but despite their presumed contribution to pain and itch, there is still limited information about organisation function. We recently identified 2 populations excitatory interneuron defined by expression gastrin-releasing peptide (GRP) or substance P (SP). Here, we demonstrate that these cells show major differences morphological, electrophysiological, pharmacological properties. Based on...
Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here, we investigate role continue to NPY (NPY-INs) adult mouse cord. We find chemogenetic activation NPY-INs reduces behaviours associated acute pain and pruritogen-evoked whereas silencing them causes exaggerated itch responses...
The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies perception of pain, itch, skin temperature. Despite its importance, our understanding this has been hampered by considerable functional molecular diversity constituent cells. Here, we use fluorescence-activated cell sorting isolate ALS neurons belonging Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters (ALS1-5) document their...
Abstract Neurons in the superficial dorsal horn that express gastrin-releasing peptide receptor (GRPR) are strongly implicated spinal itch pathways. However, a recent study reported many of these correspond to vertical cells, population interneurons believed transmit nociceptive information. In this study, we have used GRPR CreERT2 mouse line identify and target cells possess Grpr mRNA. We find highly concentrated lamina I outer part II, they all glutamatergic, account for ∼15% excitatory...
Abstract Anterolateral system (ALS) spinal projection neurons are essential for pain perception. However, these cells heterogeneous, and there has been extensive debate about the roles of ALS populations in different dimensions. We recently performed single-nucleus RNA sequencing on a developmentally-defined subset neurons, identified 5 transcriptomic populations. One these, ALS4, consists that express Sst , gene coding somatostatin, we reported were located lateral part lamina V. Here use...
Anterolateral system (ALS) projection neurons underlie perception of pain, itch and skin temperature. These cells are heterogeneous, there have therefore been many attempts to define functional populations. A recent study identified two classes ALS neuron in mouse superficial dorsal horn (SDH) based on expression the G protein-coupled receptors Tacr1 or Gpr83. It was reported that expressing these formed largely non-overlapping populations, ~60% SDH expressed Tacr1. An additional finding...
Abstract Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily laminae II inner and III. Inhibitory PVINs play an important role segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors postsynaptic distinct circuits. By comparison, relatively little is known excitatory (ePVINs) sensory processing. Here, we use neuroanatomical optogenetic approaches to show that ePVINs...
In Brief The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty assigning them functional populations. Around 15% laminae I-III express neuropeptide Y (NPY), but little known population. We therefore used a combined...
Projection neurons belonging to the anterolateral system (ALS) underlie perception of pain, skin temperature and itch. Many ALS cells are located in laminae III-V dorsal horn adjacent lateral white matter. However, relatively little is known about excitatory synaptic input these deep cells, therefore their engagement with neuronal circuitry region. We have used a recently developed mouse line, Phox2a::Cre, investigate population as “antenna cells”, which characterised by dense innervation...
The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate transmission information perceived as touch, pain, or itch. Despite importance these cells, our understanding their roles in neuronal circuitry is limited by difficulty identifying functional populations. One group that has been identified and characterized consists cells mouse express green fluorescent protein (GFP) under control prion (PrP) promoter. Previous reports suggested PrP-GFP...
C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive of action potential conduction velocity, which manifests as increase response latency. However, the impact ADS on spinal pain processing has not been explored, nor whether is altered inflammatory conditions. To investigate, compound potentials were made, from dorsal roots isolated rats with or without complete Freund9s adjuvant (CFA) hindpaw inflammation, to electrical stimulus...
Abstract A recently developed Phox2a::Cre mouse line has been shown to capture anterolateral system (ALS) projection neurons. Here, we used this test whether Phox2a-positive cells represent a distinct subpopulation among lamina I ALS We show that virtually all Phox2a can be retrogradely labelled from injections targeted on the lateral parabrachial area (LPb), and most of those in cervical cord also belong spinothalamic tract. accounted for ~ 50–60% LPb or thalamus. was preferentially...
Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive clinical disorders. Its electrophysiological correlate "wind-up," which dorsal horn spinal neurons increase their response repeated nociceptor stimulation. To understand the genetic basis summation, we undertook GWAS wind-up healthy human volunteers found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was...
Abstract Excitatory interneurons in the superficial dorsal horn (SDH) are heterogeneous, and include a class known as vertical cells, which convey information to lamina I projection neurons. We recently used pro-NPFF antibody reveal discrete population of excitatory that express neuropeptide FF (NPFF). Here, we generated new mouse line (NPFF Cre ) is knocked into Npff locus, Cre-dependent viruses reporter mice characterise NPFF cell properties. Both viral strategies labelled many cells SDH,...
Abstract The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies perception of pain, itch skin temperature. Despite its importance, our understanding this has been hampered by considerable functional molecular diversity constituent cells. Here we use fluorescence-activated cell sorting isolate ALS neurons belonging Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters (ALS1-5) document...
The superficial dorsal horn (SDH) of the spinal cord contains a diverse array neurons. vast majority these are interneurons, most which glutamatergic. These can be assigned to several populations, one is defined by expression gastrin-releasing peptide receptor (GRPR). GRPR cells thought "tertiary pruritoceptors," conveying itch information lamina I projection neurons anterolateral system (ALS). Surprisingly, we recently found that GRPR-expressing belong morphological class known as vertical...
The tachykinin peptide substance P (SP) is expressed by many interneurons and some projection neurons in the superficial dorsal horn of spinal cord. We have recently shown that SP-expressing excitatory lamina II correspond largely to a morphological class known as radial cells. However, little about their function, or synaptic connectivity. Here we use modification Brainbow technique define input SP show around half synapses (identified expression Homer) are from boutons with VGLUT2, which...
Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now source this synaptic input was not known. Here we provide evidence that it originates from a population inhibitory calretinin-expressing interneurons (iCRs), correspond to islet cells. The NP afferents can be assigned 3 functionally distinct classes (NP1-3). NP1 have been implicated pathological...
Background: Recent evidence has shown that the chemerin receptor 23 (ChemR23) represents a novel inflammatory pain target, whereby ChemR23 agonists, resolvin E1 and chemerin, can inhibit hypersensitivity, by mechanism involves normalisation of potentiated spinal cord responses. This study examined ability agonist, to modulate synaptic input lamina I neurokinin 1 expressing (NK1R+) dorsal horn neurons, which are known be crucial for manifestation pain. Results: Whole-cell patch-clamp...
ABSTRACT Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here we investigate role continue to NPY (NPY-INs) adulthood. We find chemogenetic activation NPY-INs reduces behaviours associated acute pain and pruritogen-evoked whereas silencing them causes exaggerated itch responses...
Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here, we investigate role continue to NPY (NPY-INs) adult mouse cord. We find chemogenetic activation NPY-INs reduces behaviours associated acute pain and pruritogen-evoked whereas silencing them causes exaggerated itch responses...
Transcutaneous electrical nerve stimulation (TENS) is a non-invasive, inexpensive analgesic technique used to relieve pain. It has been suggested that caffeine, an adenosine antagonist, may interfere with TENS action. This double-blind controlled pilot study investigated the effect of coffee on response in healthy human participants experiencing experimentally induced Twelve (7 female, age range = 20-41 years) took part two experiments separated by 24 h. Each experiment lasted 80 min and...