David A Andersson

David A Andersson
King's College London | KCL · Wolfson Centre for Age-Related Diseases

PhD
Pain, sensory neuron biology

About

55
Publications
9,324
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9,843
Citations
Introduction
Skills and Expertise
Additional affiliations
October 2017 - present
King's College London
Position
  • Professor (Associate)
October 2011 - September 2017
King's College London
Position
  • Lecturer

Publications

Publications (55)
Preprint
Full-text available
TRPA1 expressed in peripheral sensory neurons is important for nociception. Pharmacological inhibition or genetic ablation of TRPA1 profoundly reduces normal behavioural sensitivity to noxious cold and mechanical stimulation, as well as sensory neuron responses to mechanical stimulation. TRPA1 inhibition also reverses cold and mechanical hypersensi...
Article
Involving research users in setting priorities for research is essential to ensure the outcomes are patient-centred and maximise its value and impact. The Musculoskeletal Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across musculoskeletal disorders. The Child Health and Nutrition Research Initiative (C...
Article
Fibromyalgia syndrome (FMS) is a chronic widespread pain condition with mixed peripheral and central contributions. Patients display hypersensitivities to a spectrum of stimuli. Patients’ blunt pressure pain thresholds are typically reduced, and sometimes (∼15%) gentle brushstroke induces allodynia. However, after-sensations following these stimuli...
Poster
Full-text available
Study design and study subjects Patients were identified from The Walton Centre pain management program (PMP). Inclusion criteria were FMS of >1yr, ACR 2010 (3) or 1990 (5) , age >18yrs, and an average weekly pain of !4/10. Exclusion criteria were pregnancy/breastfeeding. A pain-free healthy control (HC) group, was recruited. Participants were reim...
Article
Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography-tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) UK-base...
Article
Chronic pain is the leading cause of life years lived with disability worldwide. The aetiology of most chronic pain conditions has remained poorly understood and there is a dearth of effective therapies. The WHO ICD-11 has categorised unexplained chronic pain states as ‘chronic primary pains’ (CPP), which are further defined by their association wi...
Article
Full-text available
Background Fibromyalgia syndrome (FMS) is the most common chronic widespread pain condition in rheumatology. Until recently, no clear pathophysiological mechanism for fibromyalgia had been established, resulting in management challenges. Recent research has indicated that serum IgGs may play a role in FMS. We undertook a research prioritisation exe...
Preprint
Full-text available
Involving research users in setting priorities for musculoskeletal research is essential to raise awareness of the unmet needs for MSK research, to ensure research outcomes are patient-centred and relevant, have a high likelihood of resulting in patient benefit, reduce research waste and increase research value and impact. In 2018, Versus Arthritis...
Article
Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizin...
Article
Introduction: Serum progesterone sulfate (P4S) concentrations increase in pregnancy and bind receptors that influence glucose homeostasis. We hypothesized that P4S modulate glucose homeostasis in pregnancy. Methods: Serum P4S were assayed using ultra-performance liquid chromatography- tandem mass spectrometry. Samples were studied in three separate...
Article
Full-text available
Fibromyalgia syndrome (FMS) is a chronic widespread pain condition of unknown aetiology. The role of temperature in FMS pain has not been reviewed systematically. The goal of this study was to review the influences of temperature on pain in FMS, from meteorological and quantitative sensory testing (QST) studies. The review was registered with Prosp...
Article
Animal models are important tools in diabetes research as ethical and logistical constraints limit access to human tissue. Beta cell dysfunction is a common contributor to the pathogenesis of most types of diabetes. Spontaneous hyperglycaemia developed in a colony of C57BL/6J mice at King's College London (KCL). Sequencing identified a mutation in...
Article
Full-text available
Stinging trees from Australasia produce remarkably persistent and painful stings upon contact of their stiff epidermal hairs, called trichomes, with mammalian skin. Dendrocnide-induced acute pain typically lasts for several hours, and intermittent painful flares can persist for days and weeks. Pharmacological activity has been attributed to small-m...
Article
Transient receptor potential melastatin 3 (TRPM3) is a nonselective cation channel that is inhibited by Gβγ subunits liberated following activation of Gαi/o protein-coupled receptors. Here, we demonstrate that TRPM3 channels are also inhibited by Gβγ released from Gαs and Gαq Activation of the Gs-coupled adenosine 2B receptor and the Gq-coupled mus...
Preprint
Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain and tenderness. The etiology and pathophysiology of fibromyalgia are unknown and there are no effective treatments. Here we show that sensory hypersensitivity in FMS is caused by autoantibodies that act by sensitizing nociceptive sensory neurons. Administration...
Article
Complex regional pain syndrome (CRPS) is a post-traumatic pain condition with an incompletely understood pathophysiological basis. Here, we have examined the cellular basis of pain in CRPS using behavioral and electrophysiological methods in mice treated with IgG from CRPS patients, in combination with a paw incision. Mice were subjected to a hind...
Article
The mechanisms responsible for painful and insensate diabetic neuropathy are not completely understood. Here, we have investigated sensory neuropathy in the Ins2 +/Akita mouse, a hereditary model of diabetes. Akita mice become diabetic soon after weaning, and we show that this is accompanied by an impaired mechanical and thermal nociception and a s...
Article
Full-text available
Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P2 and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM3 expressed in mouse dorsal roo...
Article
Sensory-guided fractionation of extracts of Tasmanian pepper berries revealed 20 drimane sesquiterpens, amongst which polygodial, warburganal, and 1β-acetoxy-9-deoxy-isomuzigadial exhibited the lowest pungency threshold concentrations on the tongue surface (0.6 - 2.8 nmol/cm2) and elicited a dose-dependent calcium influx into mTRPA1 expressing CHO...
Article
Full-text available
Cold temperature detection involves the process of sensory transduction in cutaneous primary sensory nerve terminals, which converts thermal stimuli into depolarizations of the membrane. This transformation into electrical signals is followed by the subsequent propagation of action potentials in cold-sensitive afferent nerve fibers. A large array o...
Article
Full-text available
Acetaminophen (APAP) is an effective antipyretic and one of the most commonly used analgesic drugs. Unlike antipyretic non-steroidal anti-inflammatory drugs, APAP elicits hypothermia in addition to its antipyretic effect. Here we have examined the mechanisms responsible for the hypothermic activity of APAP. Subcutaneous, but not intrathecal, admini...
Article
Full-text available
Specific peripheral sensory neurons respond to increases in extracellular osmolality but the mechanism responsible for excitation is unknown. Here we show that small increases in osmolality excite isolated mouse dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons expressing the cold-sensitive TRPM8 channel (transient receptor potential...
Article
Full-text available
Streptozotocin (STZ) induced diabetes is the most commonly used animal model of diabetes. Here we have demonstrated that intraplantar injections of low dose STZ evoke acute polymodal hypersensitivities in mice. These hypersensitivities were inhibited by a TRPA1 antagonist and were absent in TRPA1-null mice. In wildtype mice, systemic STZ treatment...
Article
TRPV1 is a well-characterised channel expressed by a subset of peripheral sensory neurons involved in pain sensation and also at a number of other neuronal and non-neuronal sites in the mammalian body. Functionally, TRPV1 acts as a sensor for noxious heat (greater than ~42 °C). It can also be activated by some endogenous lipid-derived molecules, ac...
Article
Full-text available
Diabetic neuropathy is a severe complication of long-standing diabetes and one of the major etiologies of neuropathic pain. Diabetes is associated with an increased formation of reactive oxygen species and the electrophilic dicarbonyl compound methylglyoxal (MG). Here we show that MG stimulates heterologously expressed TRPA1 in CHO cells and native...
Article
Full-text available
Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which can regulate TRPV1 activity via different mechanisms. Here we explored the possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1-arachidonoylglycerol, and not metabolite...
Article
While feverfew has been used for centuries to treat pain and headaches and is recommended for migraine treatment, the mechanism for its protective action remains unknown. Migraine is triggered by calcitonin gene-related peptide (CGRP) release from trigeminal neurons. Peptidergic sensory neurons, express a series of transient receptor potential (TRP...
Article
Full-text available
Hydrogen sulfide (H(2)S), which is produced endogenously from L-cysteine, is an irritant with pro-nociceptive actions. We have used measurements of intracellular calcium concentration, electrophysiology and behavioral measurements to show that the somatic pronociceptive actions of H(2)S require TRPA1. A H(2)S donor, NaHS, activated TRPA1 expressed...
Article
Full-text available
TRPA1 is a unique sensor of noxious stimuli and, hence, a potential drug target for analgesics. Here we show that the antinociceptive effects of spinal and systemic administration of acetaminophen (paracetamol) are lost in Trpa1(-/-) mice. The electrophilic metabolites N-acetyl-p-benzoquinoneimine and p-benzoquinone, but not acetaminophen itself, a...
Article
Full-text available
This study explores the in vivo effects of the proposed transient receptor potential ankyrin 1 (TRPA1) agonist 4-oxo-2-nonenal (4-ONE). Pharmacological inhibitors and genetically modified mice were used to investigate the ability of 4-ONE to act via TRPA1 receptors and possible mechanisms involving transient receptor potential vanilloid 1 (TRPV1)....
Article
Full-text available
J. Neurochem. (2010) 113, 692–703. The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNFα) have both been implicated in motor neurone vulnerability in amyotrophic lateral sclerosis/motor neurone disease. TNFα has been repo...
Article
Full-text available
The aim of the study is to investigate transient receptor potential ankyrin 1 (TRPA1)-induced responses in the vasculature and on blood pressure and heart rate (HR), in response to TRPA1 agonists using wild-type (WT) and TRPA1 knockout (KO) mice. TRPA1 agonists allyl isothiocyanate and cinnamaldehyde (CA) significantly increased blood flow in the s...
Article
Full-text available
The cooling agents menthol and icilin act as agonists at TRPM8 and TRPA1. In vitro, activation of TRPM8 by icilin and cold, but not menthol, is dependent on the activity of a sub-type of phospholipase A2, iPLA2. Lysophospholipids (e.g. LPC) produced by PLA2 activity can also activate TRPM8. The role of TRPA1 as a primary cold sensor in vitro is con...
Data
BEL (100 μg i.pl.) had no effect on the reduction in paw pressure (Randall-Selitto) thresholds evoked by prior intraplantar administration of either capsaicin (1 nmole) or α,βMeATP (1 μmole) in lightly restrained rats. Data show mean ± SEM for 6 rats/group. *** p < 0.001 vs vehicle.
Data
Application of acetone to the hind-paws evoked responses (paw withdrawal, flicking, licking) in wild-type Trpa1+/+ mice but had little effect in Trpa1-/- mice. Intraplantar injection of 25 mg menthol increased the responses to acetone in wild-type Trpa1+/+ but not in Trpa1-/- mice. Responses to acetone were measured 15 minutes after menthol adminis...
Data
Intraplantar administration of menthol (2.5-25 mg) induced a time- and dose-dependent reduction in ipsilateral paw withdrawal latency in restrained rats. Data show mean ± SEM for 6 rats/group. * p < 0.05, *** p < 0.001 vs vehicle.
Data
Intraplantar administration of LPC (60 μg) had no significant effect (P > 0.05) on the paw withdrawal latency to a 50°C hot plate stimulus. Data show mean ± SEM for 6 rats/group. Values compared with pre-dose latencies.
Article
There is emerging evidence that transient receptor potential (TRP) ion channels expressed in sensory neurons are important for the transduction of chemical, thermal and mechanical signals. Increasing research efforts are directed at understanding the roles of sensory TRP channels in acute and chronic pain. Studies using RNAi techniques to reduce th...
Article
Full-text available
The antifungal and amoebicidal drug clioquinol (CQ) was withdrawn from the market when it was linked to an epidemic of subacute myelo-optico-neuropathy (SMON). Clioquinol exerts its anti-parasitic actions by acting as a Cu/Zn chelator and ionophore. Here we show that local injections of CQ produce mechanical hyperalgesia and cold hypersensitivity t...
Article
Full-text available
Transient receptor potential A1 (TRPA1) is expressed in a subset of nociceptive sensory neurons where it acts as a sensor for environmental irritants, including acrolein, and some pungent plant ingredients such as allyl isothiocyanate and cinnamaldehyde. These exogenous compounds activate TRPA1 by covalent modification of cysteine residues. We have...
Article
To investigate the distribution of the transient receptor potential (TRP) A1 ion channel in the rat urinary bladder, and to study the effects of hydrogen sulfide (H(2)S) and known TRPA1 activators on micturition in conscious rats and on heterologously expressed ion channels. The expression of TRPA1 in urinary bladder was studied with fluorescence i...
Article
Full-text available
We investigated the role of phospholipase A2 (PLA2) and the effects of PLA2 products (polyunsaturated fatty acids and lysophospholipids) on the cold-sensitive channel transient receptor potential (melastatin)-8 (TRPM8), heterologously expressed in Chinese hamster ovary cells. TRPM8 responses to cold and the agonist icilin were abolished by inhibito...
Article
Full-text available
Acetaminophen (paracetamol) is a popular domestic analgesic and antipyretic agent with a weak anti-inflammatory action and a low incidence of adverse effects as compared with aspirin and other non-steroidal anti-inflammatory drugs. Here we show that acetaminophen, following deacetylation to its primary amine, is conjugated with arachidonic acid in...
Article
Full-text available
TRPM8 is a nonselective cation channel activated by cold and the cooling compounds menthol and icilin (Peier et al., 2002). Here, we have used electrophysiology and the calcium-sensitive dye Fura-2 to study the effect of pH and interactions between temperature, pH, and the two chemical agonists menthol and icilin on TRPM8 expressed in Chinese hamst...
Article
Mammals detect temperature with specialized neurons in the peripheral nervous system. Four TRPV-class channels have been implicated in sensing heat, and one TRPM-class channel in sensing cold. The combined range of temperatures that activate these channels covers a majority of the relevant physiological spectrum sensed by most mammals, with a signi...
Article
Anandamide acts as a full vanilloid receptor agonist in many bioassay systems, but it is a weak activator of primary afferents in the airways. To address this discrepancy, we compared the effect of different vanilloid receptor agonists in isolated airways and mesenteric arteries of guinea pig using preparations containing different phenotypes of th...
Article
Full-text available
Although Delta(9)-tetrahydrocannabinol (THC) produces analgesia, its effects on nociceptive primary afferents are unknown. These neurons participate not only in pain signaling but also in the local response to tissue injury. Here, we show that THC and cannabinol induce a CB(1)/CB(2) cannabinoid receptor-independent release of calcitonin gene-relate...
Article
Full-text available
Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermose...
Article
A distinct subset of sensory neurons are thought to directly sense changes in thermal energy through their termini in the skin. Very little is known about the molecules that mediate thermoreception by these neurons. Vanilloid Receptor 1 (VR1), a member of the TRP family of channels, is activated by noxious heat. Here we describe the cloning and cha...
Article
In the presence of ouabain (1 mM), acetylcholine and KCl (5 mM) evoked endothelium-independent relaxations in rat hepatic arteries. Treatment with capsaicin (10 μM), scopolamine (1 μM) or CGRP8–37 (3 μM) prevented these relaxations. Acetylcholine-induced relaxations in intact arterial segments in the presence of indomethacin (10 μM) and NG-nitro-L-...
Article
In the rat hepatic artery, the SKCa inhibitors UCL 1684 (300 nM) completely blocked, and scyllatoxin (1 μM) and d-tubocurarine (100 μM) partially inhibited EDHF relaxations when each of them was combined with charybdotoxin (300 nM). The IKCa inhibitors clotrimazole (3 μM) and 2-chlorophenyl-bisphenyl-methanol (3 μM) strongly depressed EDHF relaxati...
Article
The endogenous cannabinoid receptor agonist anandamide is a powerful vasodilator of isolated vascular preparations, but its mechanism of action is unclear. Here we show that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin-gene-related peptide (CGRP). The selective CGRP-rece...