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https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#1
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28722281/collagen-organization-regulates-stretch-initiated-pain-related-neuronal-signals-in-vitro-implications-for-structure-function-relationships-in-innervated-ligaments
#2
Sijia Zhang, Sagar Singh, Beth A Winkelstein
Injury to the spinal facet capsule, an innervated ligament with heterogeneous collagen organization, produces pain. Although mechanical facet joint trauma activates embedded afferents, it is unclear if, and how, the varied extracellular microstructure of its ligament affects sensory transduction for pain from mechanical inputs. To investigate the effects of macroscopic deformations on afferents in collagen matrices with different organizations, an in vitro neuron-collagen construct (NCC) model was used. NCCs with either randomly organized or parallel aligned collagen fibers were used to mimic the varied microstructure in the facet capsular ligament...
July 19, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28720830/effect-of-cxcl12-cxcr4-signaling-on-neuropathic-pain-after-chronic-compression-of-dorsal-root-ganglion
#3
Yang Yu, Xini Huang, Yuwei Di, Lintao Qu, Ni Fan
Neuropathic pain is a complex, chronic pain state that often accompanies tissue damage, inflammation or injury of the nervous system. However the underlying molecular mechanisms still remain unclear. Here, we showed that CXCL12 and CXCR4 were upregulated in the dorsal root ganglion (DRG) after chronic compression of DRG (CCD), and some CXCR4 immunopositive neurons were also immunopositive for the nociceptive neuronal markers IB4, TRPV1, CGRP, and substance P. The incidence and amplitude of CXCL12-induced Ca(2+) response in primary sensory neurons from CCD mice was significantly increased compared to those from control animals...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718822/a-bacterial-toxin-with-analgesic-properties-hyperpolarization-of-drg-neurons-by-mycolactone
#4
Ok-Ryul Song, Han-Byul Kim, Samuel Jouny, Isabelle Ricard, Alexandre Vandeputte, Nathalie Deboosere, Estelle Marion, Christophe J Queval, Pierre Lesport, Emmanuel Bourinet, Daniel Henrion, Seog Bae Oh, Guillaume Lebon, Guillaume Sandoz, Edouard Yeramian, Laurent Marsollier, Priscille Brodin
Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization...
July 18, 2017: Toxins
https://www.readbyqxmd.com/read/28701920/tlx3-function-in-the-dorsal-root-ganglion-is-pivotal-to-itch-and-pain-sensations
#5
Chengcheng Huang, Fumin Lu, Ping Li, Cheng Cao, Zijing Liu
Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG). As a result, Tlx3(F/F);Nav1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28701796/camk-ii-%C3%AE-down-regulation-protects-dorsal-root-ganglion-neurons-from-ropivacaine-hydrochloride-neurotoxicity
#6
Xian-Jie Wen, Xiao-Hong Li, Heng Li, Hua Liang, Chen-Xiang Yang, Han-Bing Wang
T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700339/trypsin-protease-activated-receptor-2-signaling-contributes-to-pancreatic-cancer-pain
#7
Jiao Zhu, Xue-Rong Miao, Kun-Ming Tao, Hai Zhu, Zhi-Yun Liu, Da-Wei Yu, Qian-Bo Chen, Hai-Bo Qiu, Zhi-Jie Lu
Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700081/spinal-nociceptive-circuit-analysis-with-recombinant-adeno-associated-viruses-the-impact-of-serotypes-and-promoters
#8
Karen Haenraets, Edmund Foster, Helge Johannssen, Vinnie Kandra, Noemie Frezel, Timothy Steffen, Valeria Jaramillo, Jean-Charles Paterna, Hanns Ulrich Zeilhofer, Hendrik Wildner
Recombinant adeno-associated virus (rAAV) vector-mediated gene transfer into genetically defined neuron subtypes has become a powerful tool to study the neuroanatomy of neuronal circuits in the brain and to unravel their functions. More recently this methodology has also become popular for the analysis of spinal cord circuits. To date a variety of naturally occurring AAV serotypes and genetically modified capsid variants are available but transduction efficiency in spinal neurons, target selectivity and the ability for retrograde tracing are only incompletely characterized...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28698219/the-transcription-factor-c-ebp%C3%AE-in-the-dorsal-root-ganglion-contributes-to-peripheral-nerve-trauma-induced-nociceptive-hypersensitivity
#9
Zhisong Li, Yuanyuan Mao, Lingli Liang, Shaogen Wu, Jingjing Yuan, Kai Mo, Weihua Cai, Qingxiang Mao, Jing Cao, Alex Bekker, Wei Zhang, Yuan-Xiang Tao
Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28697840/-effect-of-high-fat-diet-on-expression-of-transient-receptor-potential-vanilloid-1-in-respiratory-tract-and-dorsal-root-ganglion-of-mice
#10
Lian Zhu, Zhi-Liang Xu
OBJECTIVE: To investigate the effect of high-fat diet on the expression of transient receptor potential vanilloid 1 (TRPV1) in the respiratory system and the dorsal root ganglion (DRG) of mice, as well as its effect on the excitability of sensory neurons. METHODS: A total of 20 C57BL/6 mice were randomly divided into normal-diet (ND) group and high-fat diet (HFD) group, with 10 mice in each group. The mice were given corresponding diets and body weights were monitored...
July 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28676376/cutaneous-inflammation-regulates-thik1-expression-in-small-c-like-nociceptor-dorsal-root-ganglion-neurons
#11
William Haskins, Sergio Benitez, Juan M Mercado, Cristian G Acosta
Tandem pore-domain Halothane Inhibited K(+) channel (THIK1) is a two-pore-domain potassium channel (K2P) present in dorsal root ganglia (DRG). We previously demonstrated that THIK1 mRNA levels in the DRG dropped ipsilaterally 1day after CFA-induced cutaneous inflammation (CFA1). In this study we aimed to identify the currently unknown DRG subpopulations expressing THIK1, and to investigate the relationship between the channel and both inflammatory and spontaneous pain in normal rats. Using a combination of immunohistochemistry, western blotting and behavioural tests, we found that all small neurons and large groups of medium and large DRG neurons express THIK1...
July 1, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28676344/crispr-epigenome-editing-of-akap150-in-drg-neurons-abolishes-degenerative-ivd-induced-neuronal-activation
#12
Joshua D Stover, Niloofar Farhang, Kristofer C Berrett, Jason Gertz, Brandon Lawrence, Robby D Bowles
Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy...
July 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28674486/advanced-oxidative-protein-products-cause-pain-hypersensitivity-in-rats-by-inducing-dorsal-root-ganglion-neurons-apoptosis-via-nadph-oxidase-4-c-jun-n-terminal-kinase-pathways
#13
Ruoting Ding, Baihui Sun, Zhongyuan Liu, Xinqiang Yao, Haiming Wang, Xing Shen, Hui Jiang, Jianting Chen
Pain hypersensitivity is the most common category of chronic pain and is difficult to cure. Oxidative stress and certain cells apoptosis, such as dorsal root ganglion (DRG) neurons, play an essential role in the induction and development of pain hypersensitivity. The focus of this study is at a more specific molecular level. We investigated the role of advanced oxidative protein products (AOPPs) in inducing hypersensitivity and the cellular mechanism underlying the proapoptotic effect of AOPPs. Normal rats were injected by AOPPs-Rat serum albumin (AOPPs-RSA) to cause pain hypersensitivity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28674170/the-mnk-eif4e-signaling-axis-contributes-to-injury-induced-nociceptive-plasticity-and-the-development-of-chronic-pain
#14
Jamie K Moy, Arkady Khoutorsky, Marina N Asiedu, Bryan J Black, Jasper L Kuhn, Paulino Barragán-Iglesias, Salim Megat, Michael D Burton, Carolina C Burgos-Vega, Ohannes K Melemedjian, Scott Boitano, Josef Vagner, Christos G Gkogkas, Joseph J Pancrazio, Jeffrey S Mogil, Gregory Dussor, Nahum Sonenberg, Theodore J Price
Injury-induced sensitization of nociceptors contributes to pain states and the development of chronic pain. Inhibiting activity-dependent mRNA translation through mechanistic target of rapamycin (mTOR) and mitogen activated protein kinase (MAPK) pathways blocks the development of nociceptor sensitization. These pathways convergently signal to the eukaryotic translation initiation factor (eIF) 4F complex to regulate sensitization of nociceptors but the details of this process are ill-defined. Here we investigated the hypothesis that phosphorylation of the 5' cap-binding protein, eIF4E, by its specific kinase MAPK interacting kinase (MNK) 1/2 is a key factor in nociceptor sensitization and the development of chronic pain...
July 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28663089/sinomenine-produces-peripheral-analgesic-effects-via-inhibition-of-voltage-gated-sodium-currents
#15
Jeong-Yun Lee, Seo-Yeon Yoon, Jonghwa Won, Han-Byul Kim, Youngnam Kang, Seog Bae Oh
Sinomenium acutum has been used in traditional medicine to treat a painful disease such as rheumatic arthritis and neuralgia. Sinomenine, which is a main bioactive ingredient in Sinomenium acutum, has been reported to have an analgesic effect in diverse pain animal models. However little is known about the detailed mechanisms underlying peripheral analgesic effect of sinomenine. In the present study, we aimed to elucidate its cellular mechanism by using formalin-induced acute inflammatory pain model in mice...
June 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/28659591/alpha-lipoic-acid-suppresses-p2x-receptor-activities-and-visceral-hypersensitivity-to-colorectal-distention-in-diabetic-rats
#16
Ji Hu, Xin Qin, Zhen-Yuan Song, Pan-Pan Yang, Yu Feng, Qian Sun, Guang-Yin Xu, Hong-Hong Zhang
The present study was designed to investigate the roles of P2X3 receptors in dorsal root ganglion (DRG) neurons in colonic hypersensitivity and the effects of alpha-lipoic acid (ALA) on P2X3 receptor activity and colonic hypersensitivity of diabetic rats. Streptozotocin (STZ) was used to induce diabetic model. Abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) was recorded as colonic sensitivity. ATP-induced current density of colon-specific DRG (T13-L2 DRGs) neurons was measured with whole-cell patch clamp...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28659490/rhoa-inhibitor-treatment-at-acute-phase-of-spinal-cord-injury-may-induce-neurite-outgrowth-and-synaptogenesis
#17
Stephanie Devaux, Dasa Cizkova, Khalil Mallah, Melodie-Anne Karnoub, Zahra Laouby, Firas Kobeissy, Juraj Blasko, Serge Nataf, Laurent Pays, Celine Meriaux, Isabelle Fournier, Michel Salzet
The therapeutic use of RhoA inhibitors (RhoAi) has been experimentally tested in spinal cord injury (SCI). In order to decipher the underlying molecular mechanisms involved in such a process, an in vitro neuroproteomic-systems biology platform was developed in which the pan-proteomic profile of the dorsal root ganglia (DRG) cell line ND7/23 DRG was assessed in a large array of culture conditions using RhoAi and/or conditioned media obtained from SCI ex-vivo derived spinal cord slices. A fine mapping of the spatio-temporal molecular events of the RhoAi treatment in SCI was performed...
June 28, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28658526/reverse-pharmacogenomics-carbamazepine-normalizes-activation-and-attenuates-thermal-induced-hyperexcitability-of-sensory-neurons-due-to-nav1-7-mutation-i234t
#18
Yang Yang, Talia Adi, Philip Effraim, Lubin Chen, Sulayman D Dib-Hajj, Stephen G Waxman
BACKGROUND AND PURPOSE: Pharmacotherapy for pain currently involves trial-and-error. A previous study on inherited erythromelalgia (a genetic model of neuropathic pain due to mutations in voltage-gated sodium channel Nav1.7) used genomics, structural modeling, biophysical and pharmacological analyses to guide pharmacotherapy, and showed that carbamazepine normalizes voltage-dependence of activation of the Nav1.7-S241T mutant channel, reducing pain in patients carrying this mutation. However, whether this approach is applicable to other Nav mutations is still unknown...
June 28, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28656058/melatonin-suppresses-neuropathic-pain-via-mt2-dependent-and-independent-pathways-in-dorsal-root-ganglia-neurons-of-mice
#19
Jia-Ji Lin, Ye Lin, Tian-Zhi Zhao, Chun-Kui Zhang, Ting Zhang, Xiao-Li Chen, Jia-Qi Ding, Ting Chang, Zhuo Zhang, Chao Sun, Dai-Di Zhao, Jun-Lin Zhu, Zhu-Yi Li, Jin-Lian Li
Melatonin (Mel) and its receptors (MT1 and MT2) have a well-documented efficacy in treating different pain conditions. However, the anti-nociceptive effects of Mel and Mel receptors in neuropathic pain (NP) are poorly understood. To elucidate this process, pain behaviors were measured in a dorsal root ganglia (DRG)-friendly sciatic nerve cuffing model. We detected up-regulation of MT2 expression in the DRGs of cuff-implanted mice and its activation by the agonist 8-M-PDOT (8MP). Also, Mel attenuated the mechanical and thermal allodynia induced by cuff implantation...
2017: Theranostics
https://www.readbyqxmd.com/read/28655185/local-knockdown-of-nav1-6-relieves-pain-behaviors-induced-by-bmk-i
#20
Shichao Qin, Feng Jiang, You Zhou, Guokun Zhou, Pin Ye, Yonghua Ji
Voltage-gated sodium channels (VGSCs) in peripheral nociceptive sensory neurons are critical to transmit pain signals. BmK I purified from the venom of scorpion Buthus martensi Karsch (BmK) has been demonstrated to be the primary contributor of envenomation-associated pain. However, the role of distinct VGSCs such as Nav1.6 in the induction and maintenance of pain behaviors induced by BmK I was ambiguous. Herein, using molecular and behavioral approaches we investigated the mRNA and protein expression profiles of Nav1...
June 24, 2017: Acta Biochimica et Biophysica Sinica
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