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Sensory gating

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https://www.readbyqxmd.com/read/27927796/g9a-inhibits-creb-triggered-expression-of-mu-opioid-receptor-in-primary-sensory-neurons-following-peripheral-nerve-injury
#1
Lingli Liang, Jian-Yuan Zhao, Xiyao Gu, Shaogen Wu, Kai Mo, Ming Xiong, Brianna Marie Lutz, Alex Bekker, Yuan-Xiang Tao
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#2
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27911746/new-insight-in-cold-pain-role-of-ion-channels-modulation-and-clinical-perspectives
#3
Stéphane Lolignier, Dimitra Gkika, David Andersson, Enrico Leipold, Irina Vetter, Felix Viana, Jacques Noël, Jérôme Busserolles
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 of ion channels shapes this process; however, the precise contribution of specific ion channel subtypes to cold perception and cold pain remains elusive. This review aims at giving an update on our current understanding of the role played by TRPs, leak K(+) and voltage-gated Na(+) and K(+) channels in the transduction of cold by nociceptors and in cold-induced pain...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27874088/g9a-participates-in-nerve-injury-induced-kcna2-downregulation-in-primary-sensory-neurons
#4
Lingli Liang, Xiyao Gu, Jian-Yuan Zhao, Shaogen Wu, Xuerong Miao, Jifang Xiao, Kai Mo, Jun Zhang, Brianna Marie Lutz, Alex Bekker, Yuan-Xiang Tao
Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and neuropathic pain genesis. However, how nerve injury causes this downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase 2, also known as G9a, methylates histone H3 on lysine residue 9 to predominantly produce a dynamic histone dimethylation, resulting in condensed chromatin and gene transcriptional repression. We showed here that blocking nerve injury-induced increase in G9a rescued Kcna2 mRNA and protein expression in the axotomized DRG and attenuated the development of nerve injury-induced pain hypersensitivity...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27861889/margatoxin-bound-quantum-dots-as-a-novel-inhibitor-of-the-voltage-gated-ion-channel-kv1-3
#5
Austin B Schwartz, Anshika Kapur, Wentao Wang, Zhenbo Huang, Erminia Fardone, Goutam Palui, Hedi Mattoussi, Debra Ann Fadool
Venom-derived ion channel inhibitors have strong channel selectivity, potency, and stability; however, tracking delivery to their target can be challenging. Herein, we utilized luminescent quantum dots (QDs) conjugated to margatoxin (MgTx) as a traceable vehicle to target a voltage-dependent potassium channel, Kv1.3, which has a select distribution and well characterized role in immunity, glucose metabolism, and sensory ability. We screened both unconjugated (MgTx) and conjugated MgTx (QD-MgTx) for their ability to inhibit Shaker channels Kv1...
November 8, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27854251/nociceptive-trp-channels-sensory-detectors-and-transducers-in-multiple-pain-pathologies
#6
REVIEW
Aaron D Mickle, Andrew J Shepherd, Durga P Mohapatra
Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons...
November 14, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27843683/spinal-neuromodulation-as-a-novel-surgical-option-for-failed-back-surgery-syndrome-following-rhbmp-exuberant-bony-growth-in-instrumented-lumbar-fusion-a-case-report-and-literature-review
#7
Ramsis F Ghaly, Alexei Lissounov, Tatiana Tverdohleb, David Kohanchi, Kenneth D Candido, Nebojsa Nick Knezevic
BACKGROUND: Bone morphogenic protein (BMP) for instrumented lumbar fusion was approved in 2002, and since then has led to an increasing incidence of BMP-related neuropathic pain. These patients are usually resistant to conventional medical therapy and frequently undergo multiple surgical revisions without any pain relief. CASE DESCRIPTION: A 58-year-old male was referred to the author's outpatient clinic after four lumbar surgeries did not provide satisfactory pain relief...
2016: Surgical Neurology International
https://www.readbyqxmd.com/read/27827430/lactate-is-a-potent-inhibitor-of-the-capsaicin-receptor-trpv1
#8
Jeanne de la Roche, Isabella Walther, Waleria Leonow, Axel Hage, Mirjam Eberhardt, Martin Fischer, Peter W Reeh, Susanne Sauer, Andreas Leffler
Tissue ischemia results in an accumulation of lactate and local or systemic lactic acidosis. In nociceptive sensory neurons, lactate was reported to sensitize or activate the transient receptor potential ion channel TRPA1 and acid-sensing ion channels (ASICs). However, it is unclear how lactate modulates the TRPV1 regarded as the main sensor for acidosis in sensory neurons. In this study we investigated the effects of lactate (LA) on recombinant and native TRPV1 channels and on TRPV1-mediated release of neuropeptides from mouse nerves...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27826275/non-hierarchical-influence-of-visual-form-touch-and-position-cues-on-embodiment-agency-and-presence-in-virtual-reality
#9
Stephen C Pritchard, Regine Zopf, Vince Polito, David M Kaplan, Mark A Williams
The concept of self-representation is commonly decomposed into three component constructs (sense of embodiment, sense of agency, and sense of presence), and each is typically investigated separately across different experimental contexts. For example, embodiment has been explored in bodily illusions; agency has been investigated in hypnosis research; and presence has been primarily studied in the context of Virtual Reality (VR) technology. Given that each component involves the integration of multiple cues within and across sensory modalities, they may rely on similar underlying mechanisms...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27825784/does-comt-val158met-polymorphism-influence-p50-sensory-gating-eye-tracking-or-saccadic-inhibition-dysfunctions-in-schizophrenia
#10
Caroline Demily, Sandrine Louchart-de-la-Chapelle, Irène Nkam, Nicolas Ramoz, Pierre Denise, Alain Nicolas, Caroline Savalle, Florence Thibaut
Three electrophysiological endophenotypes are routinely studied in schizophrenia (SCZ): smooth pursuit eye movement (SPEM) dysfunction, deficits in P50 auditory-evoked potential inhibition, and saccadic inhibition deficits. The current study aimed to investigate the relationship between the COMT val158met polymorphism and these three endophenotypes. One hundred four SCZ patients (DSM-IV-R criteria) and 89 healthy controls were included in this study. P50 auditory-evoked potential inhibition, antisaccade paradigm and SPEM were analyzed...
October 27, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27798174/are-tmcs-the-mechanotransduction-channels-of-vertebrate-hair-cells
#11
David P Corey, Jeffrey R Holt
Sensory transduction in vertebrate hair cells and the molecules that mediate it have long been of great interest. Some components of the mechanotransduction apparatus have been identified, most as deafness gene products. Although prior candidates for the mechanotransduction channel have been proposed, each has faded with new evidence. Now, two strong candidates, TMC1 and TMC2 (transmembrane channel-like), have emerged from discovery of deafness genes in humans and mice. They are expressed at the right time during development: exactly at the onset of mechanosensitivity...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27798135/physiological-and-perceptual-sensory-attenuation-have-different-underlying-neurophysiological-correlates
#12
Clare E Palmer, Marco Davare, James M Kilner
: Sensory attenuation, the top-down filtering or gating of afferent information, has been extensively studied in two fields: physiological and perceptual. Physiological sensory attenuation is represented as a decrease in the amplitude of the primary and secondary components of the somatosensory evoked potential (SEP) before and during movement. Perceptual sensory attenuation, described using the analogy of a persons' inability to tickle oneself, is a reduction in the perception of the afferent input of a self-produced tactile sensation due to the central cancellation of the reafferent signal by the efference copy of the motor command to produce the action...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27798132/gi-dreadd-expression-in-peripheral-nerves-produces-ligand-dependent-analgesia-as-well-as-ligand-independent-functional-changes-in-sensory-neurons
#13
Jami L Saloman, Nicole N Scheff, Lindsey M Snyder, Sarah E Ross, Brian M Davis, Michael S Gold
: Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers. Whereas baseline heat thresholds in both male and female mice expressing Gi-DREADD were normal, 1 mg/kg clozapine-N-oxide (CNO) produced a significant 3 h increase in heat threshold that returned to baseline by 5 h after injection...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27786377/an-artificial-co2-driven-ionic-gate-inspired-by-olfactory-sensory-neurons-in-mosquitoes
#14
Xiaomeng Shang, Ganhua Xie, Xiang-Yu Kong, Zhen Zhang, Yuqi Zhang, Wei Tian, Liping Wen, Lei Jiang
A novel CO2 -driven ionic gate, mimicking the function of olfactory sensory neurons of mosquitoes, is successfully developed by functionalizing the walls of the nanochannels using 1-(4-amino-phenyl)-2,2,2-trifluoro-ethanone. This artificial nanochannel can switch between the ON-state and OFF-state in the presence and absence of CO2 , with an ultrahigh gating ratio of up to 1250, and has potential applications in CO2 -related sensing, gating, and nanofluidic systems.
October 27, 2016: Advanced Materials
https://www.readbyqxmd.com/read/27780178/reduced-excitability-and-impaired-nociception-in-peripheral-unmyelinated-fibers-from-nav1-9-null-mice
#15
Tal Hoffmann, Katrin Kistner, Richard W Carr, Mohammed A Nassar, Peter W Reeh, Christian Weidner
The upregulation of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 has previously been associated with inflammatory hyperalgesia. Na1.9 knockout (KO) mice, however, did not seem insensitive in conventional tests of acute nociception. Using electrophysiological, neurochemical, and behavioral techniques, we now show NaV1.9-null mice exhibit impaired mechanical and thermal sensory capacities and reduced electrical excitability of nociceptors. In single-fiber recordings from isolated skin, the electrical threshold of NaV1...
September 15, 2016: Pain
https://www.readbyqxmd.com/read/27779747/oscillatory-dynamics-and-functional-connectivity-during-gating-of-primary-somatosensory-responses
#16
Alex I Wiesman, Elizabeth Heinrichs-Graham, Nathan M Coolidge, James E Gehringer, Max J Kurz, Tony W Wilson
Sensory gating (SG) is a phenomenon in which neuronal responses to subsequent similar stimuli are weaker, and is thought to be an important mechanism for preventing excessive environmental stimulation from overloading shared neural resources. Although gating has been demonstrated in multiple sensory systems, the neural dynamics and developmental trajectory underlying SG remain poorly understood. Herein, we adopt a data-driven approach to map the spectro-temporal amplitude and functional connectivity (FC) dynamics that support gating in the somatosensory system (somato-SG) in healthy children and adolescents using magnetoencephalography (MEG)...
October 25, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27771197/deficient-prepulse-inhibition-of-blink-reflex-in-migraine-and-its-relation-to-allodynia
#17
Ugur Uygunoglu, Aysegul Gunduz, Harika Devrimsel Ertem, Derya Uluduz, Sabahattin Saip, Baki Goksan, Aksel Siva, Nurten Uzun, Feray Karaali-Savrun, Meral Kızıltan
OBJECTIVE: Prepulse inhibition (PPI) of the blink reflex (BR) is a reduction in BR excitability due to a conditioning stimulus, reflecting sensory gating by brainstem structures. We aimed to analyze PPI changes during a painful episode in chronic or episodic migraine and its relation to allodynia, since abnormal brainstem filtering has been hypothesized in migraine pathophysiology. METHODS: We included 20 patients with migraine during headache episode, and age- and gender-matched 22 healthy subjects...
October 19, 2016: Neurophysiologie Clinique, Clinical Neurophysiology
https://www.readbyqxmd.com/read/27770439/non-proton-ligand-sensing-domain-of-acid-sensing-ion-channel-3-is-required-for-itch-sensation
#18
Zhen Lei, Abdul Sami Shaikh, Wenshuai Zheng, Xiao Yu, Jingui Yu, Jingxin Li
Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. However, the molecular mechanisms of itch are unclear. Acid sensing ion channel 3 (ASIC3) is a sensor of acidic and primary inflammatory pain. The whole-cell patch-clamp technique was used to determine the effect of Chloroquine (CQ)on ASICs currents in primary sensory neurons or the Chinese hamster ovary (CHO) cells transfected with rat-ASIC1a or- ASIC3. Site-directed mutagenesis of plasmid was performed...
October 22, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27765744/ion-channel-mechanisms-of-rat-tail-artery-contraction-relaxation-by-menthol-involving-respectively-trpm8-activation-and-l-type-ca2-channel-inhibition
#19
Donal Melanaphy, Christopher D Johnson, Maxim V Kustov, Conall A Watson, Lyudmyla Borysova, Theodor V Burdyga, Alexander V Zholos
Transient receptor potential melastatin 8 (TRPM8) is the principal cold and menthol receptor channel. Characterized primarily for its cold-sensing role in sensory neurons, it is expressed and functional in several nonneuronal tissues, including vasculature. We previously demonstrated that menthol causes variable mechanical responses (vasoconstriction, vasodilatation, or biphasic reactions) in isolated arteries, depending on vascular tone. Here we aimed to dissect the specific ion channel mechanisms and corresponding Ca(2+) signaling pathways underlying such complex responses to menthol and other TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology, confocal Ca(2+) imaging, and ratiometric Ca(2+) recording...
December 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27761665/somatosensory-brain-function-and-gray-matter-regional-volumes-differ-according-to-exercise-history-evidence-from-monozygotic-twins
#20
Pekka Hautasaari, Andrej M Savić, Otto Loberg, Eini Niskanen, Jaakko Kaprio, Urho M Kujala, Ina M Tarkka
Associations between long-term physical activity and cortical function and brain structure are poorly known. Our aim was to assess whether brain functional and/or structural modulation associated with long-term physical activity is detectable using a discordant monozygotic male twin pair design. Nine monozygotic male twin pairs were carefully selected for an intrapair difference in their leisure-time physical activity of at least three years duration (mean age 34 ± 1 years). We registered somatosensory mismatch response (SMMR) in EEG to electrical stimulation of fingers and whole brain MR images...
October 19, 2016: Brain Topography
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