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https://www.readbyqxmd.com/read/28542617/inflammatory-and-apoptotic-remodeling-in-autonomic-nervous-system-following-myocardial-infarction
#1
Chen Gao, Kimberly Howard-Quijano, Christoph Rau, Tatsuo Takamiya, Yang Song, Kalyanam Shivkumar, Yibin Wang, Aman Mahajan
BACKGROUND: Chronic myocardial infarction (MI) triggers pathological remodeling in the heart and cardiac nervous system. Abnormal function of the autonomic nervous system (ANS), including stellate ganglia (SG) and dorsal root ganglia (DRG) contribute to increased sympathoexcitation, cardiac dysfunction and arrythmogenesis. ANS modulation is a therapeutic target for arrhythmia associated with cardiac injury. However, the molecular mechanism involved in the pathological remodeling in ANS following cardiac injury remains to be established...
2017: PloS One
https://www.readbyqxmd.com/read/28541258/paclitaxel-induced-painful-neuropathy-is-associated-with-changes-in-mitochondrial-bioenergetics-glycolysis-and-an-energy-deficit-in-dorsal-root-ganglia-neurons
#2
Natalie A Duggett, Lisa A Griffiths, Sarah J L Flatters
Painful neuropathy is the major dose-limiting side effect of paclitaxel chemotherapy. Mitochondrial dysfunction and ATP deficit have previously been shown in peripheral nerves of paclitaxel-treated rats, but the effects of paclitaxel in the DRG have not been explored. The aim of this study was to determine the bioenergetic status of DRG neurons following paclitaxel exposure in vitro and in vivo. Utilising isolated DRG neurons, we measured respiratory function under basal conditions and at maximal capacity, glycolytic function and ADP/ATP levels at three key behavioural time-points; prior to pain onset (day 7), peak pain severity and pain resolution...
May 2, 2017: Pain
https://www.readbyqxmd.com/read/28534262/inflammatory-changes-in-paravertebral-sympathetic-ganglia-in-two-rat-pain-models
#3
Ai-Ling Li, Jing-Dong Zhang, Wenrui Xie, Judith A Strong, Jun-Ming Zhang
Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy...
May 22, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28530662/pd-l1-inhibits-acute-and-chronic-pain-by-suppressing-nociceptive-neuron-activity-via-pd-1
#4
Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28529474/mir-30b-attenuates-neuropathic-pain-by-regulating-voltage-gated-sodium-channel-nav1-3-in-rats
#5
Songxue Su, Jinping Shao, Qingzan Zhao, Xiuhua Ren, Weihua Cai, Lei Li, Qian Bai, Xuemei Chen, Bo Xu, Jian Wang, Jing Cao, Weidong Zang
Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs) are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we discovered that SCN3A is the major target of miR-30b, and we then determined whether miR-30b regulated the expression of Nav1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28518122/dorsal-root-ganglion-injection-and-dorsal-root-crush-injury-as-a-model-for-sensory-axon-regeneration
#6
Menghon Cheah, James W Fawcett, Melissa R Andrews
Achieving axon regeneration after nervous system injury is a challenging task. As different parts of the central nervous system (CNS) differ from each other anatomically, it is important to identify an appropriate model to use for the study of axon regeneration. By using a suitable model, we can formulate a specific treatment based on the severity of injury, the neuronal cell type of interest, and the desired spinal tract for assessing regeneration. Within the sensory pathway, DRG neurons are responsible for relaying sensory information from the periphery to the CNS...
May 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28516219/decreased-sensory-nerve-excitation-and-bone-pain-associated-with-mouse-lewis-lung-cancer-in-trpv1-deficient-mice
#7
Hiroki Wakabayashi, Satoshi Wakisaka, Toru Hiraga, Kenji Hata, Riko Nishimura, Makoto Tominaga, Toshiyuki Yoneda
Bone pain is one of the most common and life-limiting complications of cancer metastasis to bone. Although the mechanism of bone pain still remains poorly understood, bone pain is evoked as a consequence of sensitization and excitation of sensory nerves (SNs) innervating bone by noxious stimuli produced in the microenvironment of bone metastases. We showed that bone is innervated by calcitonin gene-related protein (CGRP)(+) SNs extending from dorsal root ganglia (DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia and flinching with increased CGRP(+) SNs in bone and augmented SN excitation in DRG as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons...
May 17, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28515697/trpa1-channels-modify-trpv1-mediated-current-responses-in-dorsal-root-ganglion-neurons
#8
Takayoshi Masuoka, Makiko Kudo, Yuka Yamashita, Junko Yoshida, Noriko Imaizumi, Ikunobu Muramatsu, Matomo Nishio, Takaharu Ishibashi
The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed in a subset of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia of experimental animals, responsible for nociception. Many researches have revealed that some TRPV1-positive neurons co-express the transient receptor potential ankyrin 1 (TRPA1) channel whose activities are closely modulated by TRPV1 channel. However, it is less investigated whether the activities of TRPV1 channel are modulated by the presence of TRPA1 channel in primary sensory neurons...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28508316/trpc-channels-and-neuron-development-plasticity-and-activities
#9
Yilin Tai, Yichang Jia
In this chapter, we mainly focus on the functions of TRPC channels in brain development, including neural progenitor proliferation, neurogenesis, neuron survival, axon guidance, dendritic morphology, synaptogenesis, and neural plasticity. We also notice emerging advances in understanding the functions of TRPC channels in periphery, especially their functions in sensation and nociception in dorsal root ganglion (DRG). Because TRPC channels are expressed in all major types of glial cells, which account for at least half of total cells in the brain, TRPC channels may act as modulators for glial functions as well...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28505206/effects-of-%C3%AE-tat1-and-hdac5-on-axonal-regeneration-in-adult-neurons
#10
Shen Lin, Noelle A Sterling, Ian P Junker, Courtney T Helm, George M Smith
The role of posttranslational modifications in axonal injury and regeneration has been widely studied but there has been little consensus over the mechanism by which each modification affects adult axonal growth. Acetylation is known to play an important role in a variety of neuronal functions and its homeostasis is controlled by two enzyme families: the Histone Deacetylases (HDACs) and Histone Acetyl Transferases (HATs). Recent studies show that HDAC5 deacetylates microtubules in the axonal cytoplasm as part of an injury-induced regeneration response, but little is known about how acetylation of microtubules plays a role...
2017: PloS One
https://www.readbyqxmd.com/read/28505030/association-between-neurotrophic-factor-expression-and-pain-related-behavior-induced-by-nucleus-pulposus-applied-to-rat-nerve-root
#11
Shinobu Seki, Miho Sekiguchi, Shin-Ichi Konno
STUDY DESIGN: An experimental animal study OBJECTIVE.: To investigate the relationship between pain-related behavior and the expression of neurotrophic factors in the dorsal root ganglion (DRG) and spinal cord (SC) using a nucleus pulposus (NP) rat model. SUMMARY OF BACKGROUND DATA: Neurotrophic factors are released from activated glial cells and are associated with pain-related behavior. Nerve growth factor (NGF) is a neurotrophic factor that is induced by inflammation...
April 12, 2017: Spine
https://www.readbyqxmd.com/read/28501905/investigation-of-pain-mechanisms-by-calcium-imaging-approaches
#12
REVIEW
Michael Anderson, Qin Zheng, Xinzhong Dong
Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely on an intricate variety of extracellular factors, it is important to strive to maintain the physiological environment. Many electrophysiological techniques require the implementation of artificially-produced physiological environments and it can be difficult to assess the activity of many cells simultaneously...
May 13, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28498403/mus-musculus-microrna-449a-ameliorates-neuropathic-pain-by-decreasing-the-level-of-kcnma1-and-trpa1-and-increasing-the-level-of-tpte
#13
Shan Lu, Sichao Ma, Yunyun Wang, Tao Huang, Zhihua Zhu, Guoqing Zhao
Neuropathic pain is a nerve disorder characterized by the dysregulation of ion channels in dorsal root ganglion (DRG) neurons. MicroRNAs (miRs) may be associated with the molecular mechanisms underlying the altered levels of ion channels; however, the molecular mechanisms remain widely unknown. To investigate these mechanisms, the present study conducted a genomic analysis of miR between a unilateral spared nerve injury (SNI) model and sham control. Differentially expressed miRs between the SNI and sham groups were selected for transfection of DRG cells, a polymerase chain reaction (PCR) array analysis was subsequently performed...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28485773/curcumin-alleviates-lumbar-radiculopathy-by-reducing-neuroinflammation-oxidative-stress-and-nociceptive-factors
#14
L Xiao, M Ding, A Fernandez, P Zhao, L Jin, X Li
Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2...
May 9, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28483977/uncoupling-of-unc5c-with-polymerized-tubb3-in-microtubules-mediates-netrin-1-repulsion
#15
Qiangqiang Shao, Tao Yang, Huai Huang, Farrah Alarmanazi, Guofa Liu
Modulation of microtubule (MT) dynamics is a key event of cytoskeleton remodeling in the growth cone (GC) during axon outgrowth and pathfinding. Our previous studies have shown that the direct interaction of netrin receptor DCC and DSCAM with polymerized TUBB3, a neuron-specific MT subunit in the brain, is required for netrin-1-mediated axon outgrowth, branching and attraction. Here, we show that uncoupling of polymerized TUBB3 with netrin-1 repulsive receptor UNC5C is involved in netrin-1-mediated axonal repulsion...
May 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28480765/targeting-dorsal-root-ganglia-and-primary-sensory-neurons-for-the-treatment-of-chronic-pain
#16
Temugin Berta, Yawar Qadri, Ping-Heng Tan, Ru-Rong Ji
Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered: The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons...
May 8, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28476948/hierarchical-specification-of-pruriceptors-by-runt-domain-transcription-factor-runx1
#17
Lu Qi, Chengcheng Huang, Xiaohua Wu, Yeqi Tao, Jingjing Yan, Tianyong Shi, Cheng Cao, Lu Han, Mengsheng Qiu, Qiufu Ma, Zijing Liu, Yang Liu
The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch and others. Recent genetic and single-cell RNA sequencing studies have revealed a group of DRG neurons that could be particularly relevant for acute and chronic itch information transmission. They express the natriuretic peptide type B (NPPB), as well as a cohort of receptors and neuropeptides that have been implicated in chronic itch manifestation, including the interleukin-31 receptor IL31ra and its co-receptor Osmr, the leuktriene receptor Cysltr2, somatostatin and neurotensin...
May 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28473457/pharmacologic-characterization-of-amg8379-a-potent-and-selective-small-molecule-sulfonamide-antagonist-of-the-voltage-gated-sodium-channel-nav1-7
#18
Thomas J Kornecook, Ruoyuan Yin, Stephen Altmann, Xuhai Be, Virginia Berry, Christopher P Ilch, Michael Jarosh, Danielle Johnson, Josie H Lee, Sonya G Lehto, Joseph Ligutti, Dong Liu, Jason Luther, David Matson, Danny Ortuno, John Roberts, Kristin Taborn, Jinti Wang, Matthew M Weiss, Violeta Yu, Dawn X D Zhu, Robert T Fremeau, Bryan D Moyer
Potent and selective antagonists of the voltage-gated sodium channel NaV1.7 represent a promising avenue for the development of new chronic pain therapies. We generated a small molecule atropisomer quinolone sulfonamide antagonist AMG8379 and a less active enantiomer AMG8380. Here we show that AMG8379 potently blocks human NaV1.7 channels with an IC50 of 8.5 nM and endogenous tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglia (DRG) neurons with an IC50 of 3.1 nM in whole cell patch clamp electrophysiology assays using a voltage protocol that interrogates channels in a partially inactivated state...
May 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28468993/trpv3-modulates-nociceptive-signaling-through-peripheral-and-supraspinal-sites-in-rats
#19
Steve McGaraughty, Katharine L Chu, Jun Xu, Laura Leys, Rich J Radek, Michael J Dart, Arthur Gomtsyan, Robert G Schmidt, Philip R Kym, Jill-Desiree Brederson
TRPV3 is a non-selective cation channel activated by temperatures above 33oC, and is reported localized in keratinocytes and nervous tissue. In order to investigate a role for TRPV3 in pain modulation, we conducted a series of in vivo electrophysiological studies on spinal and brain nociceptive neurons. Structurally diverse TRPV3 receptor antagonists reduced responses of spinal WDR neurons to low-intensity mechanical stimulation in neuropathic rats, but only CNS penetrant antagonists decreased elevated spontaneous firing...
May 3, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28462488/an-oral-form-of-methylglyoxal-bis-guanylhydrazone-reduces-monocyte-activation-and-traffic-to-the-dorsal-root-ganglia-in-a-primate-model-of-hiv-peripheral-neuropathy
#20
Jessica R Lakritz, Samshita Yalamanchili, Michael J Polydefkis, Andrew D Miller, Michael S McGrath, Kenneth C Williams, Tricia H Burdo
Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages...
May 1, 2017: Journal of Neurovirology
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