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https://www.readbyqxmd.com/read/29783906/bulleyaconitine-a-attenuates-hyperexcitability-of-dorsal-root-ganglion-neurons-induced-by-spared-nerve-injury-the-role-of-preferably-blocking-nav1-7-and-nav1-3-channels
#1
Man-Xiu Xie, Jie Yang, Rui-Ping Pang, Wei-An Zeng, Han-Dong Ouyang, Yan-Qing Liu, Xian-Guo Liu
Background Oral administration of Bulleyaconitine A, an extracted diterpenoid alkaloid from Aconitum bulleyanum plants, is effective for treating chronic pain in rats and in human patients, but the underlying mechanisms are poorly understood. Results As the hyperexcitability of dorsal root ganglion neurons resulting from the upregulation of voltage-gated sodium (Nav) channels has been proved critical for development of chronic pain, we tested the effects of Bulleyaconitine A on Nav channels in rat spared nerve injury model of neuropathic pain...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29740284/ionic-mechanism-underlying-rebound-depolarization-in-medial-prefrontal-cortex-pyramidal-neurons
#2
Przemysław Kurowski, Katarzyna Grzelka, Paweł Szulczyk
Rebound depolarization (RD) occurs after membrane hyperpolarization and converts an arriving inhibitory signal into cell excitation. The purpose of our study was to clarify the ionic mechanism of RD in synaptically isolated layer V medial prefrontal cortex (mPFC) pyramidal neurons in slices obtained from 58- to 62-day-old male rats. The RD was evoked after a step hyperpolarization below -80 mV, longer than 150 ms in 192 of 211 (91%) tested neurons. The amplitude of RD was 30.6 ± 1.2 mV above the resting membrane potential (-67...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29719455/preemptive-application-of-qx-314-attenuates-trigeminal-neuropathic-mechanical-allodynia-in-rats
#3
Jeong-Ho Yoon, Jo-Young Son, Min-Ji Kim, Song-Hee Kang, Jin-Sook Ju, Yong-Chul Bae, Dong-Kuk Ahn
The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia...
May 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29718319/characterization-of-the-nile-grass-rat-as-a-unique-model-for-type-2-diabetic-polyneuropathy
#4
Jyoti Singh, Muhammad Saad Yousuf, Kelvin E Jones, Paige T M Shelemey, Twinkle Joy, Haecy Macandili, Bradley J Kerr, Douglas W Zochodne, Yves Sauvé, Klaus Ballanyi, Christine A Webber
Type 2 diabetes (T2D) has reached pandemic proportions worldwide. Almost half of T2D patients suffer from polyneuropathy that can present as paresthesia, hyperalgesia, allodynia, or hypoesthesia. Therapeutic treatment options are largely incomplete, suggesting new avenues of research are needed. Herein, we introduce the African Nile Grass rat (NGR), which develops T2D solely by diet manipulation, as a novel T2D polyneuropathy model. The purpose of this study was to first characterize T2D-induced polyneuropathy in the NGRs before highlighting their strength as a potential prediabetic model of T2D...
April 28, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29572558/modulation-of-sodium-channels-as-pharmacological-tool-for-pain-therapy-highlights-and-gaps
#5
REVIEW
Nilufar Foadi
Voltage-gated sodium channels are crucially involved in the transduction and transmission of nociceptive signals and pathological pain states. In the past decades, a lot of effort has been spent examining and characterizing biophysical properties of the different sodium channels and their role in signaling pathways. Several gains of function mutations of the sodium channels Nav1.7, Nav1.8, and Nav1.9 are associated with pain disorders. Due to their critical role in nociceptive pathways voltage-gated sodium channels are regarded interesting targets for pharmacological pain treatment...
March 23, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29509584/sodium-channel-nav1-3-is-expressed-by-polymorphonuclear-neutrophils-during-mouse-heart-and-kidney-ischemia-in-vivo-and-regulates-adhesion-transmigration-and-chemotaxis-of-human-and-mouse-neutrophils-in-vitro
#6
Marit Poffers, Nathalie Bühne, Christine Herzog, Anja Thorenz, Rongjun Chen, Faikah Güler, Axel Hage, Andreas Leffler, Frank Echtermeyer
BACKGROUND: Voltage-gated sodium channels generate action potentials in excitable cells, but they have also been attributed noncanonical roles in nonexcitable cells. We hypothesize that voltage-gated sodium channels play a functional role during extravasation of neutrophils. METHODS: Expression of voltage-gated sodium channels was analyzed by polymerase chain reaction. Distribution of Nav1.3 was determined by immunofluorescence and flow cytometry in mouse models of ischemic heart and kidney injury...
June 2018: Anesthesiology
https://www.readbyqxmd.com/read/29495239/-homocysteine-induces-calcium-overload-in-neonatal-rat-atrial-cells-through-activation-of-sodium-current-and-camk%C3%A2-%C3%AE
#7
L Han, Q B Dong, Y C Wei, A C Zheng, J X Li, K Hong, Y Q Wu, X S Cheng
Objective: To investigate the effect and related mechanism of homocysteine (Hcy) on calcium overload in neonatal rat atrial cells (NRICs). Methods: NRICs were assigned to 9 groups after culture for 3 days: (1) control group; (2) Hcy group (0, 50, 100, 200, 500 μmol/L for 48 hours); (3) antioxidant group (NAC, 10 μmol/L for 24 hours); (4) Hcy+NAC group (500 μmol/L Hcy for 48 hours, then treated with 10 μmol/L NAC for 24 hours); (5) calcium/calmodulin dependent protein kinase Ⅱδ (CaMKⅡδ) inhibitor group (KN-93, 3 μmol/L KN-93 for 5 hours); (6) specific sodium current inhibitor group (ELE, 1 μmol/L ELE for 5 hours); (7) Hcy+KN-93 group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 for 5 hours); (8) Hcy+ELE group (500 μmol/L Hcy for 48 hours, then treated with 1 μmol/L ELE for 5 hours; (9) Hcy+KN-93+ELE group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 and 1 μmol/L ELE for 5 hours)...
February 24, 2018: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29471715/the-effect-of-acute-dissociation-on-the-electrophysiological-properties-of-rat-dorsal-root-ganglion-neurons
#8
Yuanlong Song, Linlin Gao
The acutely dissociated neurons from the dorsal root ganglia (DRGs) are extensively used. The effects of acute dissociation on the properties of these neurons are, however, not clear. In this study, the action potentials (APs) were recorded from both acutely dissociated and in vivo identified DRG neurons with patch clamp and sharp electrode recording techniques, respectively. We found that acute dissociation slowed both the depolarizing and repolarizing rate of APs, and elongated the AP duration (APD). The lower recording temperature presented in the acutely dissociated neurons contributed to about 10% of these differences...
March 2018: Somatosensory & Motor Research
https://www.readbyqxmd.com/read/29470418/tetrodotoxin-a-candidate-drug-for-nav1-1-induced-mechanical-pain
#9
César Mattei
Tetrodotoxin (TTX), the mode of action of which has been known since the 1960s, is widely used in pharmacology as a specific inhibitor of voltage-gated sodium channels (Nav channels). This toxin has contributed to the characterization of the allosteric model of the Nav channel, and to discriminating TTX-sensitive and TTX-resistant subtypes. In addition to its role as a pharmacological tool, TTX is now considered a therapeutic molecule, and its development should lead to its use in certain pathologies involving Nav channels, particularly in the field of pain...
February 22, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29459435/membrane-cholesterol-depletion-as-a-trigger-of-nav1-9-channel-mediated-inflammatory-pain
#10
Muriel Amsalem, Corinne Poilbout, Géraldine Ferracci, Patrick Delmas, Francoise Padilla
Cholesterol is a major lipid component of the mammalian plasma membrane. While much is known about its metabolism, its transport, and its role in atherosclerotic vascular disease, less is known about its role in neuronal pathophysiology. This study reveals an unexpected function of cholesterol in controlling pain transmission. We show that inflammation lowers cholesterol content in skin tissue and sensory DRG culture. Pharmacological depletion of cellular cholesterol entails sensitization of nociceptive neurons and promotes mechanical and thermal hyperalgesia through the activation of voltage-gated Nav1...
April 13, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29435993/different-role-of-ttx-sensitive-voltage-gated-sodium-channel-na-v-1-subtypes-in-action-potential-initiation-and-conduction-in-vagal-airway-nociceptors
#11
M Kollarik, H Sun, R A Herbstsomer, F Ru, M Kocmalova, S N Meeker, B J Undem
KEY POINTS: The action potential initiation in the nerve terminals and its subsequent conduction along the axons of afferent nerves are not necessarily dependent on the same voltage-gated sodium channel (NaV 1) subunits. The action potential initiation in jugular C-fibres within airway tissues is not blocked by TTX; nonetheless, conduction of action potentials along the vagal axons of these nerves is often dependent on TTX-sensitive channels. This is not the case for nodose airway Aδ-fibres and C-fibres, where both action potential initiation and conduction is abolished by TTX or selective NaV 1...
April 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29410612/na-v-1-9-potentiates-oxidized-phospholipid-induced-trp-responses-only-under-inflammatory-conditions
#12
Corinna Martin, Carolin Stoffer, Milad Mohammadi, Julian Hugo, Enrico Leipold, Beatrice Oehler, Heike L Rittner, Robert Blum
Oxidized phospholipids (OxPL) like oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) were recently identified as novel proalgesic targets in acute and chronic inflammatory pain. These endogenous chemical irritants are generated in inflamed tissue and mediate their pain-inducing function by activating the transient receptor potential channels TRPA1 and TRPV1 expressed in sensory neurons. Notably, prototypical therapeutics interfering with OxPL were shown to inhibit TRP channel activation and pain behavior...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29388177/tanshinone-iia-improves-painful-diabetic-neuropathy-by-suppressing-the-expression-and-activity-of-voltage-gated-sodium-channel-in-rat-dorsal-root-ganglia
#13
Ao Ri-Ge-le, Zhuang-Li Guo, Qi Wang, Bao-Jian Zhang, Da-Wei Kong, Wen-Qiang Yang, Yan-Bing Yu, Li Zhang
Painful diabetic neuropathy (PDN) is one of the intractable complications of diabetes mellitus, which manifest as exaggerated pain perception. Previous studies showed that Tanshinone IIA (TIIA), one of the major bioactive extracts of Salvia miltiorrhiza Bunge, have obvious analgesic effect on different types of pain process, and the underlying analgesic mechanisms are not fully understood. The present study combined the behavioral, electrophysiological and biochemical methods to elucidate the analgesic mechanism of TIIA, using streptozotocin (STZ)-induced PDN rat models...
January 31, 2018: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/29374838/translational-model-systems-for-complex-sodium-channel-pathophysiology-in-pain
#14
Katrin Schrenk-Siemens, Corinna Rösseler, Angelika Lampert
Chronic pain patients are often left with insufficient treatment as the pathophysiology especially of neuropathic pain remains enigmatic. Recently, genetic variations in the genes of the voltage-gated sodium channels (Navs) were linked to inherited neuropathic pain syndromes, opening a research pathway to foster our understanding of the pathophysiology of neuropathic pain. More than 10 years ago, the rare, inherited pain syndrome erythromelalgia was linked to mutations in the subtype Nav1.7, and since then a plethora of mutations and genetic variations in this and other Nav genes were identified...
January 28, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29352377/difference-of-acute-dissociation-and-1-day-culture-on-the-electrophysiological-properties-of-rat-dorsal-root-ganglion-neurons
#15
Yuanlong Song, Miaomiao Zhang, Xiaoqing Tao, Zifen Xu, Yunjie Zheng, Minjie Zhu, Liangpin Zhang, Jinhan Qiao, Linlin Gao
The dissociated dorsal root ganglion (DRG) neurons with or without culture were widely used for investigation of their electrophysiological properties. The culture procedures, however, may alter the properties of these neurons and the effects are not clear. In the present study, we recorded the action potentials (AP) and the voltage-gated Na+ , K+ , and Ca2+ currents with patch clamp technique and measured the mRNA of Nav1.6-1.9 and Cav2.1-2.2 with real-time PCR technique from acutely dissociated and 1-day (1-d) cultured DRG neurons...
January 19, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29299961/erythromelalgia
#16
REVIEW
Peter Franz Klein-Weigel, Theresa Sophie Volz, Jutta Gisela Richter
Erythromelalgia is a rare syndrome characterized by the intermittent or, less commonly, by the permanent occurrence of extremely painful hyperperfused skin areas mainly located in the distal extremities. Primary erythromelalgia is nowadays considered to be a genetically determined neuropathic disorder affecting SCN9A, SCN10A, and SCN11A coding for NaV1.7, NaV1.8, and NaV1.9 neuronal sodium channels. Secondary forms might be associated with myeloproliferative disorders, connective tissue disease, cancer, infections, and poisoning...
February 2018: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/29229553/human-vs-mouse-nociceptors-similarities-and-differences
#17
Charlotte Rostock, Katrin Schrenk-Siemens, Jörg Pohle, Jan Siemens
The somatosensory system allows us to detect a diverse range of physical and chemical stimuli including noxious ones, which can initiate protective reflexes to prevent tissue damage. However, the sensation of pain can - under pathological circumstances - outlive its usefulness and perpetrate ongoing suffering. Rodent model systems have been tremendously useful to help understand basic mechanisms of pain perception. Unfortunately, the translation of this knowledge into novel therapies has been challenging. We have investigated similarities and differences of human and mouse peptidergic (TRKA expressing) nociceptors using dual-color fluorescence in situ hybridization of dorsal root ganglia...
December 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29213238/electrophysiological-and-pharmacological-analyses-of-na-v-1-9-voltage-gated-sodium-channel-by-establishing-a-heterologous-expression-system
#18
Xi Zhou, Zhen Xiao, Yan Xu, Yunxiao Zhang, Dongfang Tang, Xinzhou Wu, Cheng Tang, Minzhi Chen, Xiaoliu Shi, Ping Chen, Songping Liang, Zhonghua Liu
Nav 1. 9 voltage-gated sodium channel is preferentially expressed in peripheral nociceptive neurons. Recent progresses have proved its role in pain sensation, but our understanding of Nav 1.9, in general, has lagged behind because of limitations in heterologous expression in mammal cells. In this work, functional expression of human Nav 1.9 (hNav 1.9) was achieved by fusing GFP to the C-terminal of hNav 1.9 in ND7/23 cells, which has been proved to be a reliable method to the electrophysiological and pharmacological studies of hNav 1...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29194125/nav1-7-and-pain-contribution-of-peripheral-nerves
#19
Tal Hoffmann, Ohad Sharon, Jürgen Wittmann, Richard W Carr, Alina Vyshnevska, Roberto De Col, Mohammed A Nassar, Peter W Reeh, Christian Weidner
The sodium channel NaV1.7 contributes to action potential (AP) generation and propagation. Loss-of-function mutations in patients lead to congenital indifference to pain, though it remains unclear where on the way from sensory terminals to central nervous system the signalling is disrupted. We confirm that conditional deletion of NaV1.7 in advillin-expressing sensory neurons leads to impaired heat and mechanical nociception in behavioural tests. With single-fiber recordings from isolated skin, we found (1) a significantly lower prevalence of heat responsiveness to normally mechanosensitive C-fibers, although (2) the rare heat responses seemed quite vigorous, and (3) heat-induced calcitonin gene-related peptide release was normal...
March 2018: Pain
https://www.readbyqxmd.com/read/29161016/selective-voltage-gated-sodium-channel-peptide-toxins-from-animal-venom-pharmacological-probes-and-analgesic-drug-development
#20
Ying Wu, Hui Ma, Fan Zhang, Chunlei Zhang, Xiaohan Zou, Zhengyu Cao
Voltage-gated sodium channels (Navs) play critical roles in action potential generation and propagation. Nav channelopathy as well as pathological sensitization contribute to allodynia and hyperalgesia. Recent evidence has demonstrated the significant roles of Nav subtypes (Nav1.3, 1.7, 1.8, and 1.9) in nociceptive transduction, and therefore these Navs may represent attractive targets for analgesic drug discovery. Animal toxins are structurally diverse peptides that are highly potent yet selective on ion channel subtypes and therefore represent valuable probes to elucidate the structures, gating properties, and cellular functions of ion channels...
February 21, 2018: ACS Chemical Neuroscience
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