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https://www.readbyqxmd.com/read/29336514/machine-learned-analysis-of-quantitative-sensory-testing-responses-to-noxious-cold-stimulation-in-healthy-subjects
#1
I Weyer-Menkhoff, M C Thrun, J Lötsch
BACKGROUND: Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. METHOD: Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers...
January 16, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29317264/the-genetics-of-chronic-itch-gene-expression-in-the-skin-of-atopic-dermatitis-and-psoriasis-patients-with-severe-itch
#2
Leigh A Nattkemper, Hong Liang Tey, Rodrigo Valdes-Rodriguez, Helen Lee, Nicholas K Mollanazar, Christian Albornoz, Kristen M Sanders, Gil Yosipovitch
To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and non-itchy, non-lesional skin biopsies from 25 atopic dermatitis (AD) and 25 psoriasis patients and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared to healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and non-itchy skin in atopic and psoriatic subjects...
January 6, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29288650/cooling-relief-of-acute-and-chronic-itch-requires-trpm8-channels-and-neurons
#3
Radhika Palkar, Serra Ongun, Edward Catich, Natalie Li, Neil Borad, Angela Sarkisian, David D McKemy
Cooling or the application of mentholated liniments to the skin has been used to treat itch for centuries, yet remarkably little is known of how counter-stimuli such as these induce itch relief. Indeed, there is no clear consensus in the scientific literature as to whether or not cooling does in fact block the transduction of itch signals or if it is simply a placebo effect. This gap in our understanding led us to hypothesize that cooling is antipruritic and, like cooling analgesia, requires function of the cold-gated ion channel TRPM8, a receptor for menthol expressed on peripheral afferent nerve endings...
December 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29282613/regulation-of-pain-and-itch-by-trp-channels
#4
REVIEW
Carlene Moore, Rupali Gupta, Sven-Eric Jordt, Yong Chen, Wolfgang B Liedtke
Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily (TRPV1, TRPV3, and TRPV4), and finally members of the melastatin group (TRPM2, TRPM3, and TRPM8). Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory compounds targeting specific pain/itch-TRPs so that physiological protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur...
December 27, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29274843/oxaliplatin-induced-changes-in-expression-of-transient-receptor-potential-channels-in-the-dorsal-root-ganglion-as-a-neuropathic-mechanism-for-cold-hypersensitivity
#5
Akiko Chukyo, Terumasa Chiba, Toshie Kambe, Ken Yamamoto, Kazuyoshi Kawakami, Kyoji Taguchi, Kenji Abe
Transient receptor potential (TRP) receptors are involved in the development of chemotherapy-induced peripheral neuropathic pain, which is a common side effect of selected chemotherapeutic agents such as oxaliplatin. However, the precise contribution of TRPs to this condition remains unknown. Cold hypersensitivity is the hallmark of oxaliplatin-induced neuropathy, so we used a preclinical model of oxaliplatin-induced cold hypersensitivity in rats to determine the effects of oxaliplatin on TRP channels. To this end, immunohistochemistry was used to examine TRP vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and TRP melastatin 8 (TRPM8) expression in the rat dorsal root ganglion (DRG) after 4days of oxaliplatin treatment...
December 15, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29262313/molecular-prerequisites-for-diminished-cold-sensitivity-in-ground-squirrels-and-hamsters
#6
Vanessa Matos-Cruz, Eve R Schneider, Marco Mastrotto, Dana K Merriman, Sviatoslav N Bagriantsev, Elena O Gracheva
Thirteen-lined ground squirrels and Syrian hamsters are known for their ability to withstand cold during hibernation. We found that hibernators exhibit cold tolerance even in the active state. Imaging and electrophysiology of squirrel somatosensory neurons reveal a decrease in cold sensitivity of TRPM8-expressing cells. Characterization of squirrel and hamster TRPM8 showed that the channels are chemically activated but exhibit poor activation by cold. Cold sensitivity can be re-introduced into squirrel and hamster TRPM8 by transferring the transmembrane domain from the cold sensitive rat ortholog...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29247491/the-roles-of-trpv1-trpa1-and-trpm8-channels-in-chemical-and-thermal-sensitivity-of-the-mouse-oral-mucosa
#7
Tatjana I Kichko, Winfried Neuhuber, Gerd Kobal, Peter W Reeh
Spices in food and beverages and compounds in tobacco smoke interact with sensory irritant receptors of the transient receptor potential (TRP) cation channel family. TRPV1 (vanilloid type 1), TRPA1 (ankyrin 1) and TRPM8 (melastatin 8) not only elicit action potential signaling through trigeminal nerves, eventually evoking pungent or cooling sensations, but by their calcium conductance they also stimulate the release of calcitonin gene-related peptide (CGRP). This is measured as an index of neuronal activation to elucidate the chemo- and thermosensory transduction in the isolated mouse buccal mucosa of wildtypes and pertinent knockouts...
December 15, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29240420/iodine-promoted-aromatization-of-p-menthane-type-phytocannabinoids
#8
Federica Pollastro, Diego Caprioglio, Patrizia Marotta, Aniello Schiano Moriello, Luciano De Petrocellis, Orazio Taglialatela-Scafati, Giovanni Appendino
Treatment with iodine cleanly converts various p-menthane-type phytocannabinoids and their carboxylated precursors into cannabinol (CBN, 1a). The reaction is superior to previously reported protocols in terms of simplicity and substrate range, which includes not only tricyclic tetrahydrocannabinols such as Δ9-THC (2a) but also bicyclic phytocannabinoids such as cannabidiol (CBD, 3a). Lower homologues from the viridin series (2c and 3c, respectively) afforded cannabivarin (CBV), a non-narcotic compound that, when investigated against a series of ionotropic (thermo-TRPs) biological end-points of phytocannabinoids, retained the submicromolar TRPA1-activating and TRPM8-inhibiting properties of CBN, while also potently activating TRPV2...
December 14, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29238714/corneal-nerve-fiber-structure-its-role-in-corneal-function-and-its-changes-in-corneal-diseases
#9
REVIEW
Hiroshi Eguchi, Akio Hiura, Hiroshi Nakagawa, Shunji Kusaka, Yoshikazu Shimomura
Recently, in vivo confocal microscopy is used to examine the human corneal nerve fibers morphology. Corneal nerve fiber architecture and its role are studied in healthy and pathological conditions. Corneal nerves of rats were studied by nonspecific acetylcholinesterase (NsAchE) staining. NsAchE-positive subepithelial (stromal) nerve fiber has been found to be insensitive to capsaicin. Besides, NsAchE-negative but capsaicin-sensitive subbasal nerve (leash) fibers formed thick mesh-like structure showing close interconnections and exhibit both isolectin B4- and transient receptor potential vanilloid channel 1- (TRPV1-) positive...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29221175/trpm8-is-required-for-survival-and-radioresistance-of-glioblastoma-cells
#10
Dominik Klumpp, Stephanie C Frank, Lukas Klumpp, Efe C Sezgin, Marita Eckert, Lena Edalat, Martin Bastmeyer, Daniel Zips, Peter Ruth, Stephan M Huber
TRPM8 is a Ca2+-permeable nonselective cation channel belonging to the melastatin sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly overexpressed in a variety of tumor entities including glioblastoma multiforme where it reportedly contributes to tumor invasion. The present study aimed to disclose further functions of TRPM8 in glioma biology in particular upon cell injury by ionizing radiation. To this end, TCGA data base was queried to expose the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was performed to analyze the TRPM8 protein abundance in primary cultures of human glioblastoma...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217583/structure-of-the-cold-and-menthol-sensing-ion-channel-trpm8
#11
Ying Yin, Mengyu Wu, Lejla Zubcevic, William F Borschel, Gabriel C Lander, Seok-Yong Lee
Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold- and menthol-sensor in humans. We determined the cryo-electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 Å. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29175331/involvement-of-trpv3-and-trpm8-ion-channel-proteins-in-induction-of-mammalian-cold-inducible-proteins
#12
Takanori Fujita, Yu Liu, Hiroaki Higashitsuji, Katsuhiko Itoh, Koji Shibasaki, Jun Fujita, Hiroyuki Nishiyama
Cold-inducible RNA-binding protein (CIRP), RNA-binding motif protein 3 (RBM3) and serine and arginine rich splicing factor 5 (SRSF5) are RNA-binding proteins that are transcriptionally upregulated in response to moderately low temperatures and a variety of cellular stresses in mammalian cells. Induction of these cold-inducible proteins (CIPs) is dependent on transient receptor potential (TRP) V4 channel protein, but seems independent of its ion channel activity. We herein report that in addition to TRPV4, TRPV3 and TRPM8 are necessary for the induction of CIPs...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29164310/relevance-of-trpa1-and-trpm8-channels-as-vascular-sensors-of-cold-in-the-cutaneous-microvasculature
#13
REVIEW
Y Pan, D Thapa, L Baldissera, F Argunhan, A A Aubdool, S D Brain
Cold exposure is directly related to skin conditions, such as frostbite. This is due to the cold exposure inducing a vasoconstriction to reduce cutaneous blood flow and protect against heat loss. However, a long-term constriction will cause ischaemia and potentially irreversible damage. We have developed techniques to elucidate the mechanisms of the vascular cold response. We focused on two ligand-gated transient receptor potential (TRP) channels, namely, the established "cold sensors" TRP ankyrin 1 (TRPA1) and TRP melastin (TRPM8)...
November 21, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29138055/merkel-cells-sense-cooling-with-trpm8-channels
#14
Valentine Bouvier, Yann Roudaut, Nancy Osorio, Jean-Marc Aimonetti, Edith Ribot-Ciscar, Virginie Penalba, Thierry Merrot, Nicolas Lebonvallet, Christelle Le Gall-Ianotto, Laurent Misery, Patrick Delmas, Marcel Crest
In the skin, Merkel cells (MCs) connect with keratinocytes and Aβ nerve fibers to form a touch receptor which functions as a slow adapting mechanoreceptor (SA1 receptor). In human and mouse MCs, we observed an increased concentration of intracellular Ca(2+) ions in response to cold temperature and transient receptor potential melastatine 8 (TRPM8) ion channel agonists. A reduction in the response to cooling and TRPM8 agonists occurred following addition of TRPM8 antagonists, as well as in TRPM8 knockout mice...
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29130364/fluorescent-labeling-and-2-photon-imaging-of-mouse-tooth-pulp-nociceptors
#15
A Kadala, P Sotelo-Hitschfeld, Z Ahmad, P Tripal, B Schmid, A Mueller, L Bernal, Z Winter, S Brauchi, U Lohbauer, K Messlinger, J K Lennerz, K Zimmermann
Retrograde fluorescent labeling of dental primary afferent neurons (DPANs) has been described in rats through crystalline fluorescent DiI, while in the mouse, this technique was achieved with only Fluoro-Gold, a neurotoxic fluorescent dye with membrane penetration characteristics superior to the carbocyanine dyes. We reevaluated this technique in the rat with the aim to transfer it to the mouse because comprehensive physiologic studies require access to the mouse as a model organism. Using conventional immunohistochemistry, we assessed in rats and mice the speed of axonal dye transport from the application site to the trigeminal ganglion, the numbers of stained DPANs, and the fluorescence intensity via 1) conventional crystalline DiI and 2) a novel DiI formulation with improved penetration properties and staining efficiency...
November 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29115578/characterization-of-prostate-cancer-cell-progression-in-zebrafish-xenograft-model
#16
Wei Xu, Brittany A Foster, Mackenzie Richards, Kenneth R Bondioli, Girish Shah, Christopher C Green
Early diagnosis of prostate cancer (PCa) is critical for the application of efficient treatment to PCa patients. However, the majority of PCas remains indolent from several months to several years before malignancy. Current diagnosis methods have limitations in their reliability and are inefficient in time cost. Thus, an efficient in vivo PCa cell xenograft model is highly desired for diagnostic studies in PCas. In the present study we present a standardized procedure to create a PCa cell xenograft model using zebrafish (Danio rerio) as the host...
January 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29114087/the-cooling-compound-icilin-attenuates-autoimmune-neuroinflammation-through-modulation-of-the-t-cell-response
#17
Benjamin W Ewanchuk, Euan R O Allan, Amy L Warren, Rithwik Ramachandran, Robin M Yates
The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin-8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti-inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)-a CD4(+) T cell-driven murine model of MS-we found that both wild-type (WT) and TRPM8-deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation...
November 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29112508/estrogen-modulates-corneal-nociception-and-maintains-corneal-homeostasis-in-rat-eye
#18
Vinod Kumar, Vishma Pratap Sur, Rajdeep Guha, Aditya Konar, Sarbani Hazra
PURPOSE: To evaluate the role of estrogen in corneal nociception, its influence on lacrimal secretion, and development of dry eye. METHODS: Ovariectomy was performed in normal healthy female rats (OVX). Estrogen replacement was performed in a population of these rats (OVX+E). Tests for dry eye and corneal sensitivity were performed and compared with rats in proestrus (PRO) as controls. Gene expression of neuropeptides such as substance P, calcitonin gene receptor-like protein (CGRP), estrogen receptor α, TRPV1, and TRPM8 was evaluated in the cornea and trigeminal ganglion...
November 6, 2017: Cornea
https://www.readbyqxmd.com/read/29102663/signaling-pathways-relevant-to-nerve-growth-factor-induced-upregulation-of-transient-receptor-potential-m8-expression
#19
Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Jin Nakahara, Toshihiko Shimizu, Haruki Toriumi, Michisuke Yuzaki, Norihiro Suzuki
Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that primarily detects the innocuous cold. In pathological conditions, TRPM8 plays a role in the development of cold hyperalgesia/allodynia. Nerve growth factor (NGF) is an important mediator involved in various pain disorders. In the present study, the NGF-TrkA pathway increased TRPM8 expression by stabilizing TRPM8 mRNA through the actions of phosphatidylinositol 3-kinase and p38 MAP kinase. Moreover, c-Jun N-terminal kinase and Src tyrosine kinase were identified as a positive and negative regulator of TRPM8 expression, respectively, via post-transcriptional mechanisms independent of mRNA stabilization...
November 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/29099043/involvement-of-opioid-system-trpm8-and-asic-receptors-in-antinociceptive-effect-of-arrabidaea-brachypoda-dc-bureau
#20
Vinícius Peixoto Rodrigues, Cláudia Quintino da Rocha, Larissa Lucena Périco, Raquel de Cássia Dos Santos, Rie Ohara, Catarine Massucato Nishijima, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Lúcia Regina Machado da Rocha, Adair Roberto Soares Santos, Wagner Vilegas, Clélia Akiko Hiruma-Lima
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice...
November 2, 2017: International Journal of Molecular Sciences
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