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https://www.readbyqxmd.com/read/27896032/gene-expression-profile-of-sodium-channel-subunits-in-the-anterior-cingulate-cortex-during-experimental-paclitaxel-induced-neuropathic-pain-in-mice
#1
Willias Masocha
Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal pathophysiology is not fully understood. Dysregulation of sodium channel expression, studied mainly in the periphery and spinal cord level, contributes to the pathogenesis of neuropathic pain. We examined gene expression of sodium channel (Nav) subunits by real time polymerase chain reaction (PCR) in the anterior cingulate cortex (ACC) at day 7 post first administration of paclitaxel, when mice had developed paclitaxel-induced thermal hyperalgesia...
2016: PeerJ
https://www.readbyqxmd.com/read/27871874/functional-and-immuno-reactive-characterization-of-a-previously-undescribed-peptide-from-the-venom-of-the-scorpion-centruroides-limpidus
#2
Timoteo Olamendi-Portugal, Rita Restano-Cassulini, Lidia Riaño-Umbarila, Baltazar Becerril, Lourival D Possani
A previously undescribed toxic peptide named Cl13 was purified from the venom of the Mexican scorpion Centruroides limpidus. It contains 66 amino acid residues, including four disulfide bonds. The physiological effects assayed in 7 different subtypes of voltage gated Na(+)-channels, showed that it belongs to the β-scorpion toxin type. The most notorious effects were observed in subtypes Nav1.4, Nav1.5 and Nav1.6. Although having important sequence similarities with two other lethal toxins from this scorpion species (Cll1m and Cll2), the recently developed single chain antibody fragments (scFv) of human origin were not capable of protecting against Cl13...
November 18, 2016: Peptides
https://www.readbyqxmd.com/read/27815510/voltage-gated-sodium-channels-and-pain-related-disorders
#3
REVIEW
Alexandros H Kanellopoulos, Ayako Matsuyama
Voltage-gated sodium channels (VGSCs) are heteromeric transmembrane protein complexes. Nine homologous members, SCN1A-11A, make up the VGSC gene family. Sodium channel isoforms display a wide range of kinetic properties endowing different neuronal types with distinctly varied firing properties. Among the VGSCs isoforms, Nav1.7, Nav1.8 and Nav1.9 are preferentially expressed in the peripheral nervous system. These isoforms are known to be crucial in the conduction of nociceptive stimuli with mutations in these channels thought to be the underlying cause of a variety of heritable pain disorders...
December 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27780178/reduced-excitability-and-impaired-nociception-in-peripheral-unmyelinated-fibers-from-nav1-9-null-mice
#4
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/27683919/too-fast-rare-neuropathic-pain-state-associated-with-easy-activation-of-nav1-9
#5
Susanna B Park, Mark D Baker
No abstract text is available yet for this article.
September 28, 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/27608006/roles-of-voltage-gated-tetrodotoxin-sensitive-sodium-channels-nav1-3-and-nav1-7-in-diabetes-and-painful-diabetic-neuropathy
#6
REVIEW
Linlin Yang, Quanmin Li, Xinming Liu, Shiguang Liu
Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27598514/scn10a-mutation-in-a-patient-with-erythromelalgia-enhances-c-fiber-activity-dependent-slowing
#7
Andreas M Kist, Dagrun Sagafos, Anthony M Rush, Cristian Neacsu, Esther Eberhardt, Roland Schmidt, Lars Kristian Lunden, Kristin Ørstavik, Luisa Kaluza, Jannis Meents, Zhiping Zhang, Thomas Hedley Carr, Hugh Salter, David Malinowsky, Patrik Wollberg, Johannes Krupp, Inge Petter Kleggetveit, Martin Schmelz, Ellen Jørum, Angelika Lampert, Barbara Namer
Gain-of-function mutations in the tetrodotoxin (TTX) sensitive voltage-gated sodium channel (Nav) Nav1.7 have been identified as a key mechanism underlying chronic pain in inherited erythromelalgia. Mutations in TTX resistant channels, such as Nav1.8 or Nav1.9, were recently connected with inherited chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient's peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations...
2016: PloS One
https://www.readbyqxmd.com/read/27556810/biophysical-and-pharmacological-characterization-of-nav1-9-voltage-dependent-sodium-channels-stably-expressed-in-hek-293-cells
#8
Zhixin Lin, Sonia Santos, Karen Padilla, David Printzenhoff, Neil A Castle
The voltage dependent sodium channel Nav1.9, is expressed preferentially in peripheral sensory neurons and has been linked to human genetic pain disorders, which makes it target of interest for the development of new pain therapeutics. However, characterization of Nav1.9 pharmacology has been limited due in part to the historical difficulty of functionally expressing recombinant channels. Here we report the successful generation and characterization of human, mouse and rat Nav1.9 stably expressed in human HEK-293 cells...
2016: PloS One
https://www.readbyqxmd.com/read/27514480/ion-channelopathies-in-functional-gi-disorders
#9
Arthur Beyder, Gianrico Farrugia
In the gastrointestinal (GI) tract, abnormalities in secretion, absorption, motility, and sensation have been implicated in functional gastrointestinal disorders (FGIDs). Ion channels play important roles in all these GI functions. Disruptions of ion channels' ability to conduct ions can lead to diseases called ion channelopathies. Channelopathies can result from changes in ion channel biophysical function or expression due to mutations, posttranslational modification, and accessory protein malfunction. Channelopathies are strongly established in the fields of cardiology and neurology, but ion channelopathies are only beginning to be recognized in gastroenterology...
October 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27503742/familial-gain-of-function-nav1-9-mutation-in-a-painful-channelopathy
#10
Chongyang Han, Yang Yang, Rene H Te Morsche, Joost P H Drenth, Juan M Politei, Stephen G Waxman, Sulayman D Dib-Hajj
OBJECTIVE: Gain-of-function mutations in Nav1.9 have been identified in three families with rare heritable pain disorders, and in patients with painful small-fibre neuropathy. Identification and functional assessment of new Nav1.9 mutations will help to elucidate the phenotypic spectrum of Nav1.9 channelopathies. METHODS: Patients from a large family with early-onset pain symptoms were evaluated by clinical examination and genomic screening for mutations in SCN9A and SCN11A...
August 8, 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/27496104/a-gain-of-function-mutation-in-nav1-6-in-a-case-of-trigeminal-neuralgia
#11
Brian S Tanaka, Peng Zhao, Fadia B Dib-Hajj, Valerie Morisset, Simon Tate, Stephen G Waxman, Sulayman D Dib-Hajj
Idiopathic trigeminal neuralgia (TN) is a debilitating pain disorder characterized by episodic unilateral facial pain along the territory of branches of the trigeminal nerve. Human painful disorders, but not TN, have been linked to gain-of-function mutations in peripheral voltage-gated sodium channels (NaV1.7, NaV1.8 and NaV1.9). Gain-of-function mutations in NaV1.6, which is expressed in myelinated and unmyelinated CNS and peripheral nervous system neurons and supports neuronal high-frequency firing, have been linked to epilepsy but not to pain...
August 3, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27402262/-pain-and-analgesia-mutations-of-voltage-gated-sodium-channels
#12
M J Eberhardt, A Leffler
Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav1.8 and Nav1.9. A specific role for the function of nociceptive neurons was postulated for each. Whereas no selective sodium channel inhibitors have been established in the clinic so far, the relevance of all three isoforms regarding the pain sensitivity in humans is currently undergoing a remarkable verification through the translation of preclinical data into clinically manifest pictures...
July 11, 2016: Der Schmerz
https://www.readbyqxmd.com/read/27327156/changes-in-the-expression-of-voltage-gated-sodium-channels-nav1-3-nav1-7-nav1-8-and-nav1-9-in-rat-trigeminal-ganglia-following-chronic-constriction-injury
#13
Wenhua Xu, Jun Zhang, Yuanyin Wang, Liecheng Wang, Xuxia Wang
Voltage-gated sodium channels (VGSCs), especially the tetrodotoxin-sensitive Nav1.3 and Nav1.7, and the tetrodotoxin-resistant Nav1.8 and Nav1.9, have been implicated in acute and chronic neuropathic pain. The aim of this study was to investigate the expression of VGSC Nav1.3, Nav1.7, Nav1.8, and Nav1.9 after nerve injury and their roles in the development of trigeminal neuralgia (TN). We used the infraorbital nerve-chronic constriction injury model of TN in the rat. The time course of changes in the mechanical pain threshold was examined...
August 17, 2016: Neuroreport
https://www.readbyqxmd.com/read/27297039/decreased-nav1-9-channel-expression-in-hirschsprung-s-disease
#14
Anne-Marie O'Donnell, David Coyle, Prem Puri
AIM: Voltage-gated sodium channel subtype 9 (Nav1.9) are expressed in dorsal root ganglion neurons and are known to be involved in pain during inflammation. Animal studies have reported Nav1.9 channel expression in myenteric intrinsic primary afferent neurons (IPANs). More recently, a study involving Nav1.9 knockout mice showed clear evidence of colonic dysmotility. However, there are no data regarding the expression of these channels in the human intestine, thus, the aim of our study was to determine Nav1...
September 2016: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/27224030/infantile-pain-episodes-associated-with-novel-nav1-9-mutations-in-familial-episodic-pain-syndrome-in-japanese-families
#15
Hiroko Okuda, Atsuko Noguchi, Hatasu Kobayashi, Daiki Kondo, Kouji H Harada, Shohab Youssefian, Hirotomo Shioi, Risako Kabata, Yuki Domon, Kazufumi Kubota, Yutaka Kitano, Yasunori Takayama, Toshiaki Hitomi, Kousaku Ohno, Yoshiaki Saito, Takeshi Asano, Makoto Tominaga, Tsutomu Takahashi, Akio Koizumi
Painful peripheral neuropathy has been correlated with various voltage-gated sodium channel mutations in sensory neurons. Recently Nav1.9, a voltage-gated sodium channel subtype, has been established as a genetic influence for certain peripheral pain syndromes. In this study, we performed a genetic study in six unrelated multigenerational Japanese families with episodic pain syndrome. Affected participants (n = 23) were characterized by infantile recurrent pain episodes with spontaneous mitigation around adolescence...
2016: PloS One
https://www.readbyqxmd.com/read/27129924/positive-allosteric-modulators-of-%C3%AE-7-nicotinic-acetylcholine-receptors-affect-neither-the-function-of-other-ligand-and-voltage-gated-ion-channels-and-acetylcholinesterase-nor-%C3%AE-amyloid-content
#16
Hugo R Arias, Federica Ravazzini, Katarzyna M Targowska-Duda, Agnieszka A Kaczor, Dominik Feuerbach, Juan C Boffi, Piotr Draczkowski, Dirk Montag, Brandon M Brown, Ana Belén Elgoyhen, Krzysztof Jozwiak, Giulia Puia
The activity of positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (AChRs), including 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), 3-furan-2-yl-N-o-tolylacrylamide (PAM-3), and 3-furan-2-yl-N-phenylacrylamide (PAM-4), was tested on a variety of ligand- [i.e., human (h) α7, rat (r) α9α10, hα3-containing AChRs, mouse (m) 5-HT3AR, and several glutamate receptors (GluRs)] and voltage-gated (i.e., sodium and potassium) ion channels, as well as on acetylcholinesterase (AChE) and β-amyloid (Aβ) content...
July 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27112990/ultrasound-modulates-ion-channel-currents
#17
Jan Kubanek, Jingyi Shi, Jon Marsh, Di Chen, Cheri Deng, Jianmin Cui
Transcranial focused ultrasound (US) has been demonstrated to stimulate neurons in animals and humans, but the mechanism of this effect is unknown. It has been hypothesized that US, a mechanical stimulus, may mediate cellular discharge by activating mechanosensitive ion channels embedded within cellular membranes. To test this hypothesis, we expressed potassium and sodium mechanosensitive ion channels (channels of the two-pore-domain potassium family (K2P) including TREK-1, TREK-2, TRAAK; NaV1.5) in the Xenopus oocyte system...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27088781/pharmacotherapy-for-pain-in-a-family-with-inherited-erythromelalgia-guided-by-genomic-analysis-and-functional-profiling
#18
Paul Geha, Yang Yang, Mark Estacion, Betsy R Schulman, Hajime Tokuno, A Vania Apkarian, Sulayman D Dib-Hajj, Stephen G Waxman
IMPORTANCE: There is a need for more effective pharmacotherapy for chronic pain, including pain in inherited erythromelalgia (IEM) in which gain-of-function mutations of sodium channel NaV1.7 make dorsal root ganglion (DRG) neurons hyperexcitable. OBJECTIVE: To determine whether pain in IEM can be attenuated via pharmacotherapy guided by genomic analysis and functional profiling. DESIGN, SETTING, AND PARTICIPANTS: Pain in 2 patients with IEM due to the NaV1...
June 1, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27063102/evaluation-of-microtransplantation-of-rat-brain-neurolemma-into-xenopus-laevis-oocytes-as-a-technique-to-study-the-effect-of-neurotoxicants-on-endogenous-voltage-sensitive-ion-channels
#19
Edwin Murenzi, Abigail C Toltin, Steven B Symington, Molly M Morgan, John M Clark
Microtransplantation of mammalian brain neurolemma into the plasma membrane of Xenopus oocytes is used to study ion channels in their native form as they appear in the central nervous system. Use of microtransplanted neurolemma is advantageous for various reasons: tissue can be obtained from various sources and at different developmental stages; ion channels and receptors are present in their native configuration in their proper lipid environment along with appropriate auxiliary subunits; allowing the evaluation of numerous channelpathies caused by neurotoxicants in an ex vivo state...
April 7, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27038931/stromal-cell-derived-factor-1-increases-tetrodotoxin-resistant-sodium-currents-nav1-8-and-nav1-9-in-rat-dorsal-root-ganglion-neurons-via-different-mechanisms
#20
Fang Qiu, Yang Li, Qiang Fu, Yong-Yan Fan, Chao Zhu, Yan-Hong Liu, Wei-Dong Mi
Stromal cell-derived factor 1 (SDF-1)/chemokine CXC motif ligand 12 (CXCL12), a chemokine that is upregulated in dorsal root ganglion (DRG) during chronic pain models, has recently been found to play a central role in pain hypersensitivity. The purpose of present study is to investigate the functional impact of SDF-1 and its receptor, chemokine CXC motif receptor 4 (CXCR4), on two TTXR sodium channels in rat DRG using electrophysiological techniques. Preincubation with SDF-1 caused a concentration-dependent increase of Nav1...
July 2016: Neurochemical Research
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