A5024563142- Pain Mechanisms and Treatments
- Cannabis and Cannabinoid Research
- Neuropeptides and Animal Physiology
- Osteoarthritis Treatment and Mechanisms
- Neuroscience and Neuropharmacology Research
- Inflammatory mediators and NSAID effects
- Neurotransmitter Receptor Influence on Behavior
- Eicosanoids and Hypertension Pharmacology
- Sleep and Wakefulness Research
- Forensic Toxicology and Drug Analysis
- Biochemical effects in animals
- Healthcare and Venom Research
- Anesthesia and Pain Management
- Ion channel regulation and function
- Neuroscience of respiration and sleep
- Nerve injury and regeneration
- Stress Responses and Cortisol
- Ion Channels and Receptors
- Botulinum Toxin and Related Neurological Disorders
- Musculoskeletal pain and rehabilitation
- Spine and Intervertebral Disc Pathology
- Pharmacological Receptor Mechanisms and Effects
- Fatty Acid Research and Health
- Gestational Diabetes Research and Management
- Alcohol Consumption and Health Effects
University of Nottingham
2016-2025
Nottingham Biomedical Research Centre
2017-2025
Versus Arthritis
2016-2025
Queen's Medical Centre
2015-2024
University College London
1992-2024
Clatterbridge Cancer Centre NHS Foundation Trust
2024
The Royal Free Hospital
2024
National Health Service
2022
National Institute for Health Research
2022
National Institutes for Quantum Science and Technology
2022
Abstract Introduction Cannabis-based medicines have a number of therapeutic indications, including anti-inflammatory and analgesic effects. The endocannabinoid receptor system, the cannabinoid 1 (CB ) 2 endocannabinoids, are implicated in wide range physiological pathophysiological processes. Pre-clinical clinical studies demonstrated that cannabis-based drugs potential inflammatory diseases, rheumatoid arthritis (RA) multiple sclerosis. aim this study was to determine whether key elements...
Single-unit extracellular recordings of spino-parabrachial (spino-PB) neurons ( n = 53) antidromically driven from the contralateral parabrachial (PB) area were performed in lumbar cord anesthetized rats. All spino-PB located lamina I dorsal horn. Their axons exhibited conduction velocities between 2.8 and 27.8 m/s, thin myelinated fibers range. They had an extremely low spontaneous activity (median 0.064 Hz) a small excitatory receptive field (≤2 toes or pads). all activated by both...
Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation levels endocannabinoids with inhibitors fatty acid amide hydrolase (FAAH) is analgesic in models acute and inflammatory pain states. The aim this study was to determine whether local inhibition FAAH alters nociceptive responses spinal neurons nerve ligation model neuropathic Electrophysiological studies were performed 14–18 d after or sham surgery, effects inhibitor cyclohexylcarbamic 3-carbamoyl...
Monoacylglycerol lipase (MAGL) is a principal metabolic enzyme responsible for hydrolyzing the endogenous cannabinoid (endocannabinoid) 2-arachidonoylglycerol (2-AG). Selective inhibitors of MAGL offer valuable probes to further understand enzyme's function in biological systems and may lead drugs treating variety diseases, including psychiatric disorders, neuroinflammation, pain. N-Hydroxysuccinimidyl (NHS) carbamates have recently been identified as promising class serine hydrolase that...
Background: Clinical studies of osteoarthritis (OA) suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used monosodium iodoacetate (MIA) model OA joint investigate potential contribution spinal sensitization, in particular glial cell activation, behaviour this model. Experimental was induced rat by intra-articular injection MIA and (change weight bearing distal allodynia) assessed. Spinal cord microglia (Iba1 staining) astrocyte (GFAP...
To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro-inflammatory cytokines its potential relevance to inflammatory neurological disease, multiple sclerosis (MS). signalling may be anti-inflammatory neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress but effects these expression function are unknown.Immune from peripheral blood were obtained healthy volunteers patients with MS. Expression mRNA whole cells, mononuclear (PBMC) T was...
Objectives Blockade of transient receptor potential vanilloid 1 (TRPV1) with systemic antagonists attenuates osteoarthritis (OA) pain behaviour in rat models, but on-target-mediated hyperthermia has halted clinical trials. The present study investigated the for targeting TRPV1 receptors within OA joint order to produce analgesia. Methods presence human synovium was detected using western blotting and immunohistochemistry. In a model OA, levels an endogenous ligand TRPV1,...
Rheumatoid arthritis (RA) patients frequently show weak correlations between the magnitude of pain and inflammation suggesting that mechanisms other than overt peripheral contribute to in RA. We assessed changes microglial reactivity spinal excitability their contribution pain-like behaviour early stages collagen-induced (CIA) model. Mechanically evoked hypersensitivity, nociceptive withdrawal reflexes (NWRs) hind paw swelling were evaluated female Lewis rats before until 13 days following...
The endocannabinoid (EC) system has pleiotropic functions in the body. It plays a key role energy homeostasis and development of metabolic disorders being mediator relationship between gut microbiota host metabolism. In current study we explore functional interactions microbiome modulating inflammatory markers. Using data from 6 week exercise intervention (treatment n = 38 control 40) cross sectional validation cohort (n 35), measured associations 2-arachidonoylglycerol (2-AG), anandamide...
Despite a number of models nerve injury, few studies have examined how peripheral injury influences spinal somatosensory processing. Ligation two (L5‐L6) the three nerves that form sciatic produces partial denervation hindlimb. Following ligation, rats exhibited withdrawal responses to normally innocuous punctate mechanical and cooling stimuli (acetone) applied lesioned hindpaw. Such allodynia was not observed in sham‐operated rats. A significantly greater proportion neurones ligated...
Abstract Peripheral cannabinoid 2 receptors (CB receptors) modulate immune responses and attenuate nociceptive behaviour in models of acute persistent pain. The aim the present study was to investigate whether peripheral CB spinal processing innocuous noxious determine there are altered roles Effects local administration receptor agonist JWH‐133 (5 15 µg/50 µL) on mechanically evoked wide dynamic range (WDR) neurons noninflamed rats, rats with carrageenan‐induced hindpaw inflammation, sham...
Abstract Cannabinoid 2 (CB ) receptor mediated antinociception and increased levels of spinal CB mRNA are reported in neuropathic Sprague–Dawley rats. The aim this study was to provide functional evidence for a role peripheral, vs. spinal, cannabinoid 1 receptors Effects the agonist, JWH‐133, arachidonyl‐2‐chloroethylamide (ACEA), on primary afferent fibres were determined by calcium imaging studies adult dorsal root ganglion (DRG) neurons taken from sham‐operated Capsaicin (100 n m [Ca 2+ ]...
Intrathecally administered nociceptin (5, 50, 225 micrograms) dose-relatedly inhibited the C-fibre evoked wind-up and post-discharge of dorsal horn neurones, but not baseline responses. Spinal naloxone 50 micrograms, 10 reversed effects nociceptin. Thus antinociceptive role in spinal cord differs from that classical opioids.
Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic states. Endocannabinoids (ECs) are present in the cord, and inhibit nociceptive processing; levels ECs may be altered by which modulate turnover endocannabinoids vitro. Here, we investigate effect minocycline, an inhibitor activated microglia, on anandamide 2-arachidonoylglycerol (2-AG), related compound N-palmitoylethanolamine (PEA), cord. Selective nerve ligation (SNL) rats resulted mechanical...
Abstract Objective To investigate the impact of an experimental model osteoarthritis (OA) on spinal nociceptive processing and role inhibitory endocannabinoid system in regulating sensory at level. Methods Experimental OA was induced rats by intraarticular injection sodium mono‐iodoacetate (MIA), development pain behavior assessed. Extracellular single‐unit recordings wide dynamic range (WDR) neurons dorsal horn were obtained MIA‐treated saline‐treated rats. The levels endocannabinoids...