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TRPV1

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https://www.readbyqxmd.com/read/29772784/capsaicin-in-metabolic-syndrome
#1
REVIEW
Sunil K Panchal, Edward Bliss, Lindsay Brown
Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders...
May 17, 2018: Nutrients
https://www.readbyqxmd.com/read/29768956/-express-attenuation-of-trpv1-by-amg-517-after-nerve-injury-promotes-peripheral-axonal-regeneration-in-rats
#2
Juan Bai, F U Liu, Li-Fei Wu, Ya-Fang Wang, Xia-Qing Li
AIMS: The main objective was to investigate the effects of the transient receptor potential cation channel subfamily V member 1 (TRPV1) on nerve regeneration following sciatic transection injury by functional blockage of TRPV1 using AMG-517, a specific blocker of TRPV1. METHODS: AMG-517 was injected into the area surrounding ipsilateral lumbar dorsal root ganglia (DRGs) 30 min after unilateral sciatic nerve transection. The number of sciatic axons and the expression of growth associated protein-43 (GAP-43) and glial fibrillary acidic protein (GFAP) were examined using semi-thin sections, western blot, and immunofluorescence analyses...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29768498/genomic-variants-in-an-inbred-mouse-model-predict-mania-like-behaviors
#3
Michael C Saul, Sharon A Stevenson, Changjiu Zhao, Terri M Driessen, Brian E Eisinger, Stephen C Gammie
Contemporary rodent models for bipolar disorders split the bipolar spectrum into complimentary behavioral endophenotypes representing mania and depression. Widely accepted mania models typically utilize single gene transgenics or pharmacological manipulations, but inbred rodent strains show great potential as mania models. Their acceptance is often limited by the lack of genotypic data needed to establish construct validity. In this study, we used a unique strategy to inexpensively explore and confirm population allele differences in naturally occurring candidate variants in a manic rodent strain, the Madison (MSN) mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29765535/effects-of-cb2-and-trpv1-receptors-stimulation-in-pediatric-acute-t-lymphoblastic-leukemia
#4
Francesca Punzo, Iolanda Manzo, Chiara Tortora, Elvira Pota, Velia D' Angelo, Giulia Bellini, Alessandra Di Paola, Federica Verace, Fiorina Casale, Francesca Rossi
T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy. The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752146/a-novel-topical-nonsteroidal-trpv1-antagonist-pac-14028-cream-improves-skin-barrier-function-and-exerts-anti-inflammatory-action-through-modulating-epidermal-differentiation-markers-and-suppressing-th2-cytokines-in-atopic-dermatitis
#5
Ji-Hae Lee, Chang Soon Choi, Il-Hong Bae, Jin Kyu Choi, Young-Ho Park, Miyoung Park
BACKGROUND: Although it is established that epidermal barrier disturbance and immune dysfunction resulting in IgE sensitization are critical factors in the development of cutaneous inflammation, the pathogenesis and targeted therapy of atopic dermatitis (AD)-specific pathways have still been unknown. OBJECTIVE: Taking into account the fact that Th2 cytokines in AD have both unique and overlapping functions including increased epidermal thickening, inflammation, and decreased expressing of the barrier proteins keratinocyte differentiation, we sought to clarify our hypothesis that TRPV1 antagonist plays a critical role in skin barrier function and can be a therapeutic target for AD...
April 30, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29746988/connexin36-expression-in-primary-afferent-neurons-in-relation-tothe-axon-reflex-modality-coding-of-somatic-sensation
#6
J I Nagy, B D Lynn, J M M Senecal, K Stecina
Electrical coupling mediated by connexin36-containing gap junctions that form electrical synapses is known to be prevalent in the central nervous system, but such coupling was long ago reported also to occur between cutaneous sensory fibers. Here, we provide evidence supporting the capability of primary afferent fibers to engage in electrical coupling. In transgenic mice with enhanced green fluorescent protein (eGFP) serving as a reporter for connexin36 expression, immunofluorescence labelling of eGFP was found in subpopulations of neurons in lumbar dorsal root and trigeminal sensory ganglia, and in fibers within peripheral nerves and tissues...
May 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29746471/atypical-pharmacology-of-schistosome-trpa1-like-ion-channels
#7
Swarna Bais, Corbett T Berry, Xiaohong Liu, Gordon Ruthel, Bruce D Freedman, Robert M Greenberg
Parasitic flatworms of the genus Schistosoma cause schistosomiasis, a neglected tropical disease estimated to affect over 200 million people worldwide. Praziquantel is the only antischistosomal currently available for treatment, and there is an urgent need for new therapeutics. Ion channels play key roles in physiology and are targets for many anthelmintics, yet only a few representatives have been characterized in any detail in schistosomes and other parasitic helminths. The transient receptor potential (TRP) channel superfamily comprises a diverse family of non-selective cation channels that play key roles in sensory transduction and a wide range of other functions...
May 10, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29742796/hdac-inhibition-inhibits-brachial-plexus-avulsion-induced-neuropathic-pain
#8
Yingbo Zhao, Tianjian Wu
Introduction Neuropathic pain induced by brachial plexus avulsion (BPA) is a pathological condition. We hypothesized that inhibition of histone deacetylase (HDAC) could suppress BPA-induced neuropathic pain through inhibition of transient reception potential (TRP) overexpression and protein kinase B (Akt) mediated mammalian target of rapamycin (mTOR) activation. Methods We generated a rat BPA model, administered HDAC inhibitor Tricostatin A (TSA) for 7 days post-surgery and assessed the effects on HDAC expression, Akt phosphorylation, neuroinflammation and mTOR activation...
May 9, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29740328/emerging-role-of-endo-cannabinoids-in-migraine
#9
REVIEW
Pinja Leimuranta, Leonard Khiroug, Rashid Giniatullin
In this mini-review, we summarize recent discoveries and present new hypotheses on the role of cannabinoids in controlling trigeminal nociceptive system underlying migraine pain. Individual sections of this review cover key aspects of this topic, such as: (i) the current knowledge on the endocannabinoid system (ECS) with emphasis on expression of its components in migraine related structures; (ii) distinguishing peripheral from central site of action of cannabinoids, (iii) proposed mechanisms of migraine pain and control of nociceptive traffic by cannabinoids at the level of meninges and in brainstem, (iv) therapeutic targeting in migraine of monoacylglycerol lipase and fatty acid amide hydrolase, enzymes which control the level of endocannabinoids; (v) dual (possibly opposing) actions of cannabinoids via anti-nociceptive CB1 and CB2 and pro-nociceptive TRPV1 receptors...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29740093/differential-contributions-of-peripheral-and-central-mechanisms-to-pain-in-a-rodent-model-of-osteoarthritis
#10
Adrian R Haywood, Gareth J Hathway, Victoria Chapman
The mechanisms underlying the transition from acute nociceptive pain to centrally maintained chronic pain are not clear. We have studied the contributions of the peripheral and central nervous systems during the development of osteoarthritis (OA) pain. Male Sprague-Dawley rats received unilateral intra-articular injections of monosodium iodoacetate (MIA 1 mg) or saline, and weight-bearing (WB) asymmetry and distal allodynia measured. Subgroups of rats received intra-articular injections of, QX-314 (membrane impermeable local anaesthetic) + capsaicin, QX-314, capsaicin or vehicle on days 7, 14 or 28 post-MIA and WB and PWT remeasured...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739958/trpv1-and-the-mcp-1-ccr2-axis-modulate-post-uti-chronic-pain
#11
John M Rosen, Ryan E Yaggie, Patrick J Woida, Richard J Miller, Anthony J Schaeffer, David J Klumpp
The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29735654/identification-of-cytokine-specific-sensory-neural-signals-by-decoding-murine-vagus-nerve-activity
#12
Theodoros P Zanos, Harold A Silverman, Todd Levy, Tea Tsaava, Emily Battinelli, Peter W Lorraine, Jeffrey M Ashe, Sangeeta S Chavan, Kevin J Tracey, Chad E Bouton
The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29735636/potential-protective-mechanism-in-the-cardiac-microvascular-injury
#13
Xiuchuan Li, Juanni Hou, Jin Du, Jian Feng, Yi Yang, Yang Shen, Sha Chen, Juan Feng, Dachun Yang, De Li, Haifeng Pei, Yongjian Yang
Cardiac microvascular injury often occurs in patients with type 2 diabetes mellitus (T2DM) who develop hyperglycemia and hyperlipidemia. However, besides reported contradictory roles in cardiac diseases, the function of TRPV1 (transient receptor potential vanilloid 1) in cardiac microvessels is not well defined. This study was performed to determine the detailed role of TRPV1 in cardiac microvascular endothelial cells (CMECs) in T2DM. T2DM mice were established by multiple injections of low-dose streptozotocin and high-fat feeding...
May 7, 2018: Hypertension
https://www.readbyqxmd.com/read/29734380/mitochondrial-modulation-induced-activation-of-vagal-sensory-neuronal-subsets-by-antimycin-a-but-not-cccp-or-rotenone-correlates-with-mitochondrial-superoxide-production
#14
Katherine R Stanford, Thomas E Taylor-Clark
Inflammation causes nociceptive sensory neuron activation, evoking debilitating symptoms and reflexes. Inflammatory signaling pathways are capable of modulating mitochondrial function, resulting in reactive oxygen species (ROS) production, mitochondrial depolarization and calcium release. Previously we showed that mitochondrial modulation with antimycin A, a complex III inhibitor, selectively stimulated nociceptive bronchopulmonary C-fibers via the activation of transient receptor potential (TRP) ankyrin 1 (A1) and vanilloid 1 (V1) cation channels...
2018: PloS One
https://www.readbyqxmd.com/read/29734335/pomc-neurons-in-heat-a-link-between-warm-temperatures-and-appetite-suppression
#15
Maria A Vicent, Conor L Mook, Matthew E Carter
When core body temperature increases, appetite and food consumption decline. A higher core body temperature can occur during exercise, during exposure to warm environmental temperatures, or during a fever, yet the mechanisms that link relatively warm temperatures to appetite suppression are unknown. A recent study in PLOS Biology demonstrates that neurons in the mouse hypothalamus that express pro-opiomelanocortin (POMC), a neural population well known to suppress food intake, also express a temperature-sensitive ion channel, transient receptor potential vanilloid 1 (TRPV1)...
May 7, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29733975/role-of-trpv1-and-trpv4-in-surgical-incision-induced-tissue-swelling-and-fos-like-immunoreactivity-in-the-central-nervous-system-of-mice
#16
Yasuhito Motojima, Haruki Nishimura, Hiromichi Ueno, Satomi Sonoda, Kazuaki Nishimura, Kentaro Tanaka, Reiko Saito, Mitsuhiro Yoshimura, Takashi Maruyama, Takanori Matsuura, Hitoshi Suzuki, Makoto Kawasaki, Hideo Ohnishi, Akinori Sakai, Yoichi Ueta
Pain management remains a major concern regarding the treatment of postoperative patients. Transient receptor potential (TRP) channels are considered to be new therapeutic targets for pain control. We investigated whether the genes Trpv1 and Trpv4 are involved in hind paw swelling caused after surgical incision in mice or in incision-induced Fos-like immunoreactivity (Fos-LI) levels in the central nervous system. Mice were divided into four groups: wild-type (WT) control, WT incision, Trpv1 knockout (Trpv1-/- ) incision, and Trpv4 knockout (Trpv4-/- ) incision...
May 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29732984/knockout-of-trpv1-exacerbates-left-ventricular-diastolic-dysfunction-induced-by-a-high-fat-diet-in-mice
#17
Beihua Zhong, Jack Rubinstein, Shuangtao Ma, Donna H Wang
BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) channels in sensory nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1 knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction. METHOD: Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we performed the intraperitoneal glucose tolerance test, measured the heart function through transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac histology, and measured the myocardial superoxide production and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases...
May 3, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29730242/potentiation-of-capsaicin-induced-neurogenic-inflammation-by-5-ht7-receptors-in-the-rat-hind-paw-involvement-of-calcitonin-gen-related-peptide
#18
Luis D Arreola-Peralta, Frida Altamirano-Reyna, Deni M Galindo-González, Jessica G Solis-Anguiano, Enza Lacivita, Marcello Leopoldo, José A Terrón
A decrease in the activation threshold of primary sensory neurons to transient receptor potential V1 (TRPV1) stimulation by serotonin 5-HT7 receptors has been reported but no confirmation if this might translate into facilitation of neurogenic inflammation has been provided. We analysed the modulation of capsaicin (CAP)-induced neurogenic inflammation in the rat hind paw by the selective 5-HT7 receptor agonist, LP-44, and the involvement of calcitonin gen-related peptide (CGRP) in this effect. Animals received intra-plantar injections (30 μl) of vehicle, CAP (0...
May 3, 2018: Peptides
https://www.readbyqxmd.com/read/29729263/enhanced-endocannabinoid-tone-as-a-potential-target-of-pharmacotherapy
#19
REVIEW
Marek Toczek, Barbara Malinowska
The endocannabinoid system is up-regulated in numerous pathophysiological states such as inflammatory, neurodegenerative, gastrointestinal, metabolic and cardiovascular diseases, pain, and cancer. It has been suggested that this phenomenon primarily serves an autoprotective role in inhibiting disease progression and/or diminishing signs and symptoms. Accordingly, enhancement of endogenous endocannabinoid tone by inhibition of endocannabinoid degradation represents a promising therapeutic approach for the treatment of many diseases...
May 2, 2018: Life Sciences
https://www.readbyqxmd.com/read/29729213/manipulating-trpv1-antagonists-how-to-cool-down-a-hot-molecule
#20
EDITORIAL
Leon Islas, Arpad Szallasi
TRPV1 is a promising pain target. Although a number of small molecule TRPV1 antagonists have been advanced into clinical trials, thus far none has progressed beyond Phase II due to on-target side-effects such as a febrile reaction. In this issue of Acta Physiologica, Romanovsky and colleagues report two TRPV1 antagonists that paradoxically induce hypothermia in experimental animals, potentially opening a new avenue for drug development. This article is protected by copyright. All rights reserved.
May 5, 2018: Acta Physiologica
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