A5021322976- Pain Mechanisms and Treatments
- Cannabis and Cannabinoid Research
- Osteoarthritis Treatment and Mechanisms
- Neuroscience and Neuropharmacology Research
- Inflammatory mediators and NSAID effects
- Neuropeptides and Animal Physiology
- Healthcare and Venom Research
- Forensic Toxicology and Drug Analysis
- Sleep and Wakefulness Research
- Musculoskeletal pain and rehabilitation
- Ion Channels and Receptors
- Neurotransmitter Receptor Influence on Behavior
- Alcohol Consumption and Health Effects
- Veterinary Pharmacology and Anesthesia
- Mesenchymal stem cell research
- Biochemical effects in animals
- Neuroscience of respiration and sleep
- Analytical Methods in Pharmaceuticals
- Palliative Care and End-of-Life Issues
- Nerve injury and regeneration
- LGBTQ Health, Identity, and Policy
- Bone Metabolism and Diseases
- Antibiotics Pharmacokinetics and Efficacy
- Pharmacological Effects of Natural Compounds
- Eicosanoids and Hypertension Pharmacology
Marie Curie
2023
University of Nottingham
2010-2022
Versus Arthritis
2013-2022
Queen's Medical Centre
2008-2018
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...
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,...
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+ ]...
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...
Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA An improved understanding how pathology impacts upon processing pain crucial for identification novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate neuro-immune responses in models neurodegeneration. Systemic...
Background Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). Objectives To investigate the analgesic potential of a modified version osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) monosodium iodoacetate (MIA) model OA pain. Methods Male Sprague Dawley rats (140–260 g) were treated with either OPG-Fc (3 mg/kg, subcutaneously) or vehicle (phosphate-buffered saline) between days 1 and 27 (pre-emptive treatment) 21 (therapeutic after an intra-articular injection...
We have previously demonstrated antinociceptive effects of fatty acid amide hydrolase (FAAH) inhibition that were accompanied by increases in the levels endocannabinoids (ECs) hind paw. Here, FAAH inhibitor URB597 (3'-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) on responses spinal neurons studied.Extracellular single-unit recordings dorsal horn made anaesthetized rats with paw inflammation induced lambda-carrageenan. Effects intraplantar pre-administration URB597, or vehicle,...
Anxiety and depression are associated with increased pain responses in chronic states. The extent to which anxiety drives pain, or vice versa, remains an important question that has implications for analgesic treatment strategies. Here, the effect of existing on future osteoarthritis (OA) was investigated, potential mechanisms were studied animal model. Pressure detection thresholds, anxiety, assessed people (n = 130) without 100) painful knee OA. Separately, scores also measured twice over...
N-arachidonoyl-dopamine (NADA) is an endogenous ligand at TRPV1 and CB(1) receptors, which are expressed on primary afferent nociceptors. The aim of this study was to determine contributions proposed pronociceptive antinociceptive receptors effects peripheral NADA fibre function. Effects nociceptor function, determined by whole cell patch clamp calcium imaging studies adult dorsal root ganglion (DRG) neurons, were determined. Application (1 microm) DRG neurons depolarized the resting...
We describe a novel LC method for the simultaneous and quantitative profiling of 43 oxylipins including eicosanoids, endocannabinoids, structurally related bioactive lipids with modified acyl groups. The LC-MS/MS uses switching at defined time between negative positive electrospray ionization modes to achieve optimal detection sensitivity all lipids. validated is linear over range 0.01-5 nmol/g (0.1-50 2-arachidonoyl glycerol) intra- interday precision accuracy 1.38 26.76% 85.22 114.3%,...
The presence of cannabinoid1 (CB1) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. present study investigated the ability peripheral CB1 to modulate innocuous and noxious transmission in noninflamed rats with carrageenan inflammation. Effects injection arachidonyl-2-choroethylamide (ACEA; 10 30 micro g 50 L), selective receptor agonist, mechanically evoked responses dorsal horn neurons were studied Peripheral ACEA (30 L) significantly inhibited (12...
Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain clinical interest, neurophysiological mechanisms by which NGF contribute to OA unclear. We investigated impact local elevation knee joint on joint, vs remote (hindpaw), evoked responses spinal neurones in a rodent model pain.In vivo electrophysiology was carried out anaesthetised rats with established behaviour and pathology following intra-articular injection monosodium...
BackgroundThe mechanisms driving osteoarthritic pain remain poorly understood, but there is increasing evidence for a role of the central nervous system in chronification pain. We used functional magnetic resonance imaging to investigate influence model unilateral knee osteoarthritis on nociceptive processing. ResultsFour five weeks post intra-articular injection monosodium iodoacetate (MIA, 1 mg) into left knee, Sprague Dawley rats were anesthetized studies characterize neural response...
Abstract Models of neuropathic pain are associated with elevated spinal levels endocannabinoids (ECs) and altered expression cannabinoid receptors on primary sensory afferents post‐synaptic cells in the cord. We investigated impact these changes processing inputs a model pain. Extracellular single‐unit recordings neurones were made anaesthetized sham‐operated rats. The effects administration CB 1 receptor antagonist N...
Mesenchymal stem cells (MSCs) have a therapeutic potential for the treatment of osteoarthritic (OA) joint pathology and pain. The aims this study were to determine influence passage number on effects MSCs pain behaviour cartilage bone features in rodent model OA. Rats underwent either medial meniscal transection (MNX) or sham surgery under anaesthesia. received intra-articular injection 1.5 × 106 late labelled with 10 μg/ml SiMAG, mesenchymal cells, steroid Kenalog (200 μg/20 μL), early...
Abstract Neuroimmune interactions across the pain pathway play a predominant role in development of neuropathic pain. Previous reports demonstrated that complement driven effector systems including C5a/C5aR1 axis contribute to these neuro-immune mechanisms. However, cellular and molecular mechanisms underlying signaling-mediated remain ill-identified. Here we show following peripheral nerve injury was attenuated C5aR1-deficient male female mice as well wild type treated with selective...