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https://www.readbyqxmd.com/read/29339292/selective-hcn1-block-as-a-strategy-to-control-oxaliplatin-induced-neuropathy
#1
F Resta, L Micheli, A Laurino, V Spinelli, T Mello, L Sartiani, L Di Cesare Mannelli, E Cerbai, C Ghelardini, M N Romanelli, G Mannaioni, A Masi
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies...
January 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#2
Cui-Cui Liu, Zhu-Xi Huang, Xiao Li, Kai-Feng Shen, Meng Liu, Han-Dong Ouyang, Su-Bo Zhang, Yu-Ting Ruan, Xiao-Long Zhang, Shao-Ling Wu, Wen-Jun Xin, Chao Ma
Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29336505/signalling-transduction-events-involved-in-agonist-induced-pge2-ep4-receptor-externalization-in-cultured-rat-dorsal-root-ganglion-neurons
#3
W Ma, B St-Jacques
BACKGROUND: Prostaglandin E2 (PGE2) enriched in inflamed tissues contributes to chronic pain by sensitizing nociceptive dorsal root ganglion (DRG) neurons (nociceptors). Of four PGE2 receptors (EP1-4), EP4 plays a major role in PGE2-induced nociceptor sensitization. We have previously reported that PGE2 or EP4 agonists stimulated EP4 externalization in cultured DRG neurons and this event contributes to nociceptor sensitization. However, the signalling transduction events governing this event remain unknown...
January 16, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29335509/salient-type-1-interleukin-1-receptor-expression-in-peripheral-non-immune-cells
#4
Anping Song, Ling Zhu, Gowthami Gorantla, Olimpia Berdysz, Stephanie A Amici, Mireia Guerau-de-Arellano, Kathryn M Madalena, Jessica K Lerch, Xiaoyu Liu, Ning Quan
Interleukin 1 is a pleiotropic cytokine that mediates diverse functions through its receptor, type I interleukin 1 receptor (IL-1R1). Most previous studies have focused on the expression and function of IL-1R1 in immune cells. Here we performed a comprehensive mapping of IL-1R1 distribution in multiple peripheral tissues using our IL-1R1 reporter (IL-1R1GR/GR) mice. This method yielded the highest sensitivity of in situ detection of IL-1R1 mRNA and protein. Besides validating previously reported IL-1R1 expression in the endocrine tissues including pituitary and pancreas, our results refuted previously reported exclusive IL-1R1 expression in neurons of the spinal cord dorsal horn and dorsal root ganglia (DRG)...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29335353/kchip3-n-terminal-31-50-fragment-mediates-its-association-with-trpv1-and-alleviates-inflammatory-hyperalgesia-in-rats
#5
Na-Xi Tian 田纳西, Yu Xu 徐煜, Jin-Yu Yang 杨瑾裕, Lu Li 李璐, Xiao-Hong Sun 孙晓红, Yun Wang 王韵, Ying Zhang 张瑛
Potassium channel interacting protein 3 (KChIP3), also termed downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a multi-functional protein belonging to the neuronal calcium sensor (NCS) family. Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG) neurons, suggesting the potential role of KChIP3 in peripheral sensory processing. Herein, we show that KChIP3 co-localizes with TRPV1, a critical molecule involved in peripheral sensitization during inflammatory pain...
January 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29333591/differential-inhibition-of-nav1-7-and-neuropathic-pain-by-hybridoma-produced-and-recombinant-monoclonal-antibodies-that-target-nav1-7-differential-activities-of-nav1-7-targeting-monoclonal-antibodies
#6
Sangsu Bang, Jiho Yoo, Xingrui Gong, Di Liu, Qingjian Han, Xin Luo, Wonseok Chang, Gang Chen, Sang-Taek Im, Yong Ho Kim, Judith A Strong, Ma-Zhong Zhang, Jun-Ming Zhang, Seok-Yong Lee, Ru-Rong Ji
The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1...
January 15, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29330377/phenotypic-and-functional-characterization-of-peripheral-sensory-neurons-derived-from-human-embryonic-stem-cells
#7
Abdullah Jawad Alshawaf, Serena Viventi, Wanzhi Qiu, Giovanna D'Abaco, Bryony Nayagam, Michael Erlichster, Gursharan Chana, Ian Everall, Jason Ivanusic, Efstratios Skafidas, Mirella Dottori
The dorsal root ganglia (DRG) consist of a multitude of sensory neuronal subtypes that function to relay sensory stimuli, including temperature, pressure, pain and position to the central nervous system. Our knowledge of DRG sensory neurons have been predominantly driven by animal studies and considerably less is known about the human DRG. Human embryonic stem cells (hESC) are valuable resource to help close this gap. Our previous studies reported an efficient system for deriving neural crest and DRG sensory neurons from hESC...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329586/il-33-st2-signaling-contributes-to-radicular-pain-by-modulating-mapk-and-nf-%C3%AE%C2%BAb-activation-and-inflammatory-mediator-expression-in-the-spinal-cord-in-rat-models-of-noncompressive-lumber-disk-herniation
#8
Si-Jian Huang, Jian-Qin Yan, Hui Luo, Lu-Yao Zhou, Jian-Gang Luo
BACKGROUND: Immune and inflammatory responses occurring in the spinal cord play a pivotal role in the progression of radicular pain caused by intervertebral disk herniation. Interleukin-33 (IL-33) orchestrates inflammatory responses in a wide range of inflammatory and autoimmune disorders of the nervous system. Thus, the purpose of this study is to investigate the expression of IL-33 and its receptor ST2 in the dorsal spinal cord and to elucidate whether the inhibition of spinal IL-33 expression significantly attenuates pain-related behaviors in rat models of noncompressive lumbar disc herniation...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29317663/trpv1-enhances-the-afferent-response-to-p2x-receptor-activation-in-the-mouse-urinary-bladder
#9
Luke Grundy, Donna M Daly, Christopher Chapple, David Grundy, Russ Chess-Williams
Both TRPV1 and P2X receptors present on bladder sensory nerve fibres have been implicated in mechanosensation during bladder filling. The aim of this study was to determine possible interactions between these receptors in modulating afferent nerve activity. In wildtype (TRPV1+/+) and TRPV1 knockout (TRPV1-/-) mice, bladder afferent nerve activity, intravesical pressure, and luminal ATP and acetylcholine levels were determined and also intracellular calcium responses of dissociated pelvic DRG neurones and primary mouse urothelial cells (PMUCs)...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29308980/modulation-of-trpa1-channel-activity-by-cdk5-in-sensory-neurons
#10
Michael A Sulak, Monica Ghosh, Pritam Sinharoy, Spencer R Andrei, Derek S Damron
Transient receptor potential cation channel, subfamily A, member 1 (TRPA1), is activated by a broad range of noxious stimuli. Cdk5, a member of the Cdk family, has recently been identified as a modulator of pain signaling pathways. In the current study, we investigated the extent to which Cdk5 modulates TRPA1 activity. Cdk5 inhibition was found to attenuate TRPA1 response to agonist in mouse DRG sensory neurons. Additionally, the presence of active Cdk5 was associated with increased TRPA1 phosphorylation in transfected HEK293 cells that was roscovitine-sensitive and absent in the mouse mutant S449A full-length channel...
January 8, 2018: Channels
https://www.readbyqxmd.com/read/29305237/isolation-of-satellite-glial-cells-for-high-quality-rna-purification
#11
Sara Buskbjerg Jager, Lone Tjener Pallesen, Christian Bjerggaard Vaegter
BACKGROUND: Satellite glial cells (SGCs) envelope the neuronal somas in the dorsal root ganglia (DRG) and are believed to provide important neuronal support. Animal models of peripheral nerve injury, diabetes or chemotherapy all demonstrate activation of SGCs, suggesting important physiological roles for SGCs in various states of peripheral neuropathy. However, the biology of these glial cells is only poorly characterized under normal as well as pathological conditions due to suboptimal isolation methods...
January 2, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29303989/characterization-of-different-types-of-excitability-in-large-somatosensory-neurons-and-its-plastic-changes-in-pathological-pain-states
#12
Rou-Gang Xie, Wen-Guang Chu, San-Jue Hu, Ceng Luo
Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive...
January 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29296613/mglur2-3-activation-of-the-sirt1-axis-preserves-mitochondrial-function-in-diabetic-neuropathy
#13
Krish Chandrasekaran, Anjaneyulu Muragundla, Tyler G Demarest, Joungil Choi, Avinash R Sagi, Neda Najimi, Pranith Kumar, Anmol Singh, Cheng-Ying Ho, Gary Fiskum, Lauren G Koch, Steven L Britton, James W Russell
Objectives: There is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function. Methods: Adult male streptozotocin treated Sprague-Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268...
December 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29291392/urothelial-bladder-afferent-neurons-in-the-rat-are-anatomically-and-neurochemically-distinct-from-non-urothelial-afferents
#14
Buffie J Clodfelder-Miller, Hirosato Kanda, Jianguo G Gu, Judy R Creighton, Timothy J Ness, Jennifer J DeBerry
There is mounting evidence underscoring a role for the urothelium in urinary bladder sensation. Previous functional studies have identified bladder primary afferents with mechanosensitive properties suggesting urothelial innervation and/or communication. The current study identifies a group of urothelium-innervating afferent neurons in rat, and characterizes and compares the properties of these and non-urothelial afferent neuron populations. Lumbosacral (LS) primary afferent neurons were retrogradely labeled using intraparenchymal (IPar) microinjection or intravesical (IVes) infusion of tracer into the bladder...
December 29, 2017: Brain Research
https://www.readbyqxmd.com/read/29286468/analysis-of-immune-cells-in-single-sciatic-nerves-and-dorsal-root-ganglion-from-a-single-mouse-using-flow-cytometry
#15
Asa S Hidmark, Peter P Nawroth, Thomas Fleming
Nerve-resident immune cells in the peripheral nervous system (PNS) are essential to maintaining neuronal integrity in a healthy nerve. The immune cells of the PNS are affected by injury and disease, affecting the nerve function and the capacity for regeneration. Neuronal immune cells are commonly analyzed by immunofluorescence (IF). While IF is essential for determining the location of the immune cells in the nerve, IF is only semi-quantitative and the method is limited to the number of markers that can be analyzed simultaneously and the degree of surface expression...
December 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29275446/distinct-expression-of-phenotypic-markers-in-placodes-and-neural-crest-derived-afferent-neurons-innervating-the-rat-stomach
#16
Alzbeta Trancikova, Eva Kovacova, Fei Ru, Kristian Varga, Mariana Brozmanova, Milos Tatar, Marian Kollarik
BACKGROUND: Visceral pain is initiated by activation of primary afferent neurons among which the capsaicin-sensitive (TRPV1-positive) neurons play an important role. The stomach is a common source of visceral pain. Similar to other organs, the stomach receives dual spinal and vagal afferent innervation. Developmentally, spinal dorsal root ganglia (DRG) and vagal jugular neurons originate from embryonic neural crest and vagal nodose neurons originate from placodes. In thoracic organs the neural crest- and placodes-derived TRPV1-positive neurons have distinct phenotypes differing in activation profile, neurotrophic regulation and reflex responses...
December 23, 2017: Digestive Diseases and Sciences
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
#17
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/29273526/activation-of-the-capsaicin-receptor-trpv1-by-the-acetaminophen-metabolite-n-arachidonoylaminophenol-results-in-cytotoxicity
#18
Thomas Stueber, Susanne Meyer, Annette Jangra, Axel Hage, Mirjam Eberhardt, Andreas Leffler
AIMS: The anandamide reuptake inhibitor N-arachidonoylaminophenol (AM404) and the reactive substance N-acetyl-p-benzoquinone imine (NAPQI) are both metabolites of acetaminophen and may contribute to acetaminophen-induced analgesia by acting at TRPV1 expressed in the peripheral or central nervous system. While NAPQI slowly sensitizes and activates TRPV1 by interacting with distinct intracellular cysteine residues, detailed properties of AM404 as an agonist of TRPV1 have not yet been reported on...
December 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/29273519/adenosine-monophosphate-activated-protein-kinase-modulation-by-berberine-attenuates-mitochondrial-deficits-and-redox-imbalance-in-experimental-diabetic-neuropathy
#19
Veera Ganesh Yerra, Anil Kumar Kalvala, Bhoomika Sherkhane, Aparna Areti, Ashutosh Kumar
Adenosine monophosphate activated protein kinase (AMPK) has been studied for its myriad metabolic and mitochondrial benefits in several chronic diseases. Recent studies have uncovered its therapeutic potential against mitochondrial dysfunction in cultured dorsal root ganglion (DRG) neurons isolated from streptozotocin (STZ) induced diabetic rats. The present study is aimed at evaluating the pharmacological efficacy of berberine (BRB), a natural AMPK activator against experimental diabetic neuropathy (DN) phenotype developed in STZ (55 mg/kg, i...
December 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29260523/-the-role-of-long-chain-non-coding-rna-paupar-in-the-process-of-bupivacaine-induced-neurotoxicity
#20
Li-Liang Zhang, Li-Na Qi, Ze-Yu Yao
OBJECTIVE: To observe the expression mode and modulation effects of lncRNA-Paupar in the process of bupivacaine induced neurotoxicity. METHODS: Dorsal root ganglion (DRG) neurons were cultured and neurotoxicity model was produced on it. And the expression of lncRNA-Paupar was evaluated by qRT-PCR. Lnc-Paupar specific siRNA-P and random control group siRNA-C were constructed,200 nmol/L siRNA-P,siRNA-C were transfected into ganglion cells and the apoptosis rate of transfected cells were observed by TUNEL method...
November 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
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