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Ablation or modulation of the dorsal root ganglion

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https://www.readbyqxmd.com/read/29106982/distinct-trka-and-ret-modulated-negative-and-positive-neuropathic-behaviors-in-a-mouse-model-of-resiniferatoxin-induced-small-fiber-neuropathy
#1
Yu-Lin Hsieh, Hung-Wei Kan, Hao Chiang, Yi-Chen Lee, Sung-Tsang Hsieh
Neurotrophic factors and their corresponding receptors play key roles in the maintenance of different phenotypic dorsal root ganglion (DRG) neurons, the axons of which degenerate in small fiber neuropathy, leading to various neuropathic manifestations. Mechanisms underlying positive and negative symptoms of small fiber neuropathy have not been systematically explored. This study investigated the molecular basis of these seemingly paradoxical neuropathic behaviors according to the profiles of TrkA and Ret with immunohistochemical and pharmacological interventions in a mouse model of resiniferatoxin (RTX)-induced small fiber neuropathy...
October 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29089436/protease-mediated-suppression-of-drg-neuron-excitability-by-commensal-bacteria
#2
Jessica L Sessenwein, Corey C Baker, Sabindra Pradhananga, Megan E Maitland, Elaine O Petrof, Emma Allen-Vercoe, Curtis Noordhof, David E Reed, Stephen J Vanner, Alan E Lomax
Peripheral pain signaling reflects a balance of pro and anti-nociceptive influences; the contribution by the gastrointestinal (GI) microbiota to this balance has received little attention. Disorders such as inflammatory bowel disease and irritable bowel syndrome are associated with exaggerated visceral nociceptive actions that may involve altered microbial signaling, particularly given the evidence for bacterial dysbiosis. Thus, we tested whether a community of commensal GI bacteria derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) can affect the excitability of male mouse dorsal root ganglion (DRG) neurons...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29044528/endomorphins-potentiate-asic-currents-and-enhance-the-lactic-acid-mediated-increase-in-arterial-blood-pressure-effects-amplified-in-hindlimb-ischemia
#3
Mohamed Farrag, Julie K Drobish, Henry L Puhl, Joyce S Kim, Paul B Herold, Marc P Kaufman, Victor Ruiz-Velasco
Chronic muscle ischemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex...
October 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29025860/negative-regulation-of-trpa1-by-amp-activated-protein-kinase-in-primary-sensory-neurons-as-a-potential-mechanism-of-painful-diabetic-neuropathy
#4
Shenglan Wang, Kimiko Kobayashi, Yoko Kogure, Hiroki Yamanaka, Satoshi Yamamoto, Hideshi Yagi, Koichi Noguchi, Yi Dai
AMP activated protein kinase (AMPK) is a widely expressed intracellular energy sensor that monitors and modulates energy expenditure. Transient receptor potential ankyrin 1 (TRPA1) channel is a widely recognized chemical and thermal sensor that plays vital roles in pain transduction. Here, we discovered a functional link between AMPK and TRPA1 in dorsal root ganglion (DRG) neurons, in which AMPK activation rapidly resulted in downregulation of membrane-associated TRPA1 and its channel activity within minutes...
October 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28975573/effects-of-voluntary-exercise-on-antiretroviral-therapy-induced-neuropathic-pain-in-mice
#5
Hong Ye, Xingguang Du, Qingli Hua
Antiretroviral therapy (ART) often results in painful peripheral neuropathy. Given that voluntary exercise has been shown to be beneficial in terms of modulating pain-like behaviors in various animal models of peripheral neuropathy, we have investigated the effects of voluntary wheel running on neuropathic pain induced by chronic ART. We first established an animal model of peripheral neuropathy induced by chronic 2',3'-dideoxycytidine (ddC) treatment. We showed that mice receiving ddC (3 mg/kg/day) had increased mechanical and thermal sensitivity at 9 weeks after the onset of the treatment...
October 3, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28952182/effects-of-duloxetine-on-pain-and-walking-distance-in-neuropathic-pain-models-via-modulation-of-the-spinal-monoamine-system
#6
K Minami, R Tamano, E Kasai, H Oyama, M Hasegawa, S Shinohara, T Asaki
BACKGROUND: Approximately 40% of patients with chronic low back pain have a neuropathic component. In this study, we assessed the effects of analgesics on tactile hypersensitivity and walking distance in the rat cauda equina compression (CEC) model of neuropathic low back pain. METHODS: The effects of analgesics on tactile hypersensitivity were examined using the von Frey test in CEC and partial sciatic nerve ligation (pSNL) models. Effects on walking distance were assessed using a treadmill test...
September 26, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28924864/a-nociceptive-role-for-integrin-signaling-in-pain-after-mechanical-injury-to-the-spinal-facet-capsular-ligament
#7
Sijia Zhang, Ethan Zhao, Beth A Winkelstein
Integrins modulate chemically-induced nociception in a variety of inflammatory and neuropathic pain models. Yet, the role of integrins in mechanically-induced pain remains undefined, despite its well-known involvement in cell adhesion and mechanotransduction. Excessive spinal facet capsular ligament stretch is a common injury that induces morphological and functional changes in its innervating afferent neurons and can lead to pain. However, the local mechanisms underlying the translation from tissue deformation to pain signaling are unclear, impeding effective treatment...
December 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28899795/microrna-137-and-its-downstream-target-lsd1-inversely-regulate-anesthetics-induced-neurotoxicity-in-dorsal-root-ganglion-neurons
#8
Lingyang Chen, Xiaodan Wang, Wenguang Huang, Tingting Ying, Minjuan Chen, Jianbin Cao, Mingcang Wang
PURPOSE: Anesthetic reagents, such as bupivacaine (Bv), induce significant neurotoxicity in dorsal root ganglion neurons (DRGNs). In this study, we investigated the expression, function and cross-association of microRNA-137-3p (miR-137-3p) and lysine (K)-specific demethylase 1A (LSD1) in a murine model of Bv-induced neural injury in DRGNs. METHODS: Murine DRGNs were culture in vitro and treated with Bv. QPCR was used to evaluate miR-137-3p expression in Bv-injured DRGNs...
September 9, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28882562/candesartan-prevents-resiniferatoxin-induced-sensory-small-fiber-neuropathy-in-mice-by-promoting-angiotensin-ii-mediated-at2-receptor-stimulation
#9
Flavien Bessaguet, Aurore Danigo, Laurent Magy, Franck Sturtz, Alexis Desmoulière, Claire Demiot
Sensory defects associated with small-fiber neuropathy (SFN) can lead to profound disabilities. The relationship between the sensory nervous system and modulation of the renin-angiotensin system (RAS) has been described and focused on pain and neurodegeneration in several animal models. We have recently developed an experimental model of functional sensory neuropathy showing thermal hypoalgesia and neuropeptide depletion without nerve fiber degeneration. Here, we aimed to determine whether the modulation of angiotensin II (Ang II) activity could prevent sensory neuropathy induced by RTX...
September 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28871264/neuroinflammation-bone-marrow-stem-cells-and-chronic-pain
#10
REVIEW
Yul Huh, Ru-Rong Ji, Gang Chen
Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS) plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG)], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain), and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL)-1β, IL-6, CCL2, and CXCL1]...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28867384/downregulations-of-trpm8-expression-and-membrane-trafficking-in-dorsal-root-ganglion-mediate-the-attenuation-of-cold-hyperalgesia-in-cci-rats-induced-by-gfr%C3%AE-3-knockdown
#11
Lin Su, Ruichen Shu, Chengcheng Song, Yonghao Yu, Guolin Wang, Yazhuo Li, Changxiao Liu
BACKGROUND: Cold hyperalgesia is an intractable sensory abnormality commonly seen in peripheral neuropathies. Although glial cell line-derived neurotrophic factor family receptor alpha3 (GFRα3) is required for the formation of pathological cold pain has been revealed, potential transduction mechanism is poorly elucidated. We have previously demonstrated the contribution of enhanced activity of transient receptor potential melastatin 8 (TRPM8) to cold hyperalgesia in neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve...
September 1, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28846565/swimming-training-reduces-neuroma-pain-by-regulating-neurotrophins
#12
Tian Jinge, Zhang Xin, Yu Tingting, Xu Yongming, Pu Shaofeng, Lv Yingying, Du Dongping
INTRODUCTION: Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested physical exercise could bring beneficial effect on alleviating neuropathic pain. Yet the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NTs), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting following nerve injury...
August 25, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28826490/g-protein-%C3%AE-%C3%AE-subunits-inhibit-trpm3-ion-channels-in-sensory-neurons
#13
Talisia Quallo, Omar Alkhatib, Clive Gentry, David A Andersson, Stuart Bevan
Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P2 and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM3 expressed in mouse dorsal root ganglion (DRG) neurons is inhibited by agonists of the Gi-coupled µ opioid, GABA-B and NPY receptors. These agonist effects are mediated by direct inhibition of TRPM3 by Gβγ subunits, rather than by a canonical cAMP mediated mechanism...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28813592/3d-printed-phema-materials-for-topographical-and-biochemical-modulation-of-dorsal-root-ganglion-cell-response
#14
Adina Badea, Joselle M McCracken, Emily G Tillmaand, Mikhail E Kandel, Aaron W Oraham, Molly B Mevis, Stanislav S Rubakhin, Gabriel Popescu, Jonathan V Sweedler, Ralph G Nuzzo
Understanding and controlling the interactions occurring between cells and engineered materials are central challenges toward progress in the development of biomedical devices. In this work, we describe materials for direct ink writing (DIW), an extrusion-based type of 3D printing, that embed a custom synthetic protein (RGD-PDL) within the microfilaments of 3D-hydrogel scaffolds to modify these interactions and differentially direct tissue-level organization of complex cell populations in vitro. The RGD-PDL is synthesized by modifying poly-d-lysine (PDL) to varying extents with peptides containing the integrin-binding motif Arg-Gly-Asp (RGD)...
September 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28751455/calcineurin-dysregulation-underlies-spinal-cord-injury-induced-k-channel-dysfunction-in-drg-neurons
#15
Benjamin M Zemel, Tanziyah Muqeem, Eric V Brown, Miguel Goulão, Mark W Urban, Stephen R Tymanskyj, Angelo C Lepore, Manuel Covarrubias
Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3...
August 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28734869/p2x-receptors-up-regulate-the-cell-surface-expression-of-the-neuronal-glycine-transporter-glyt2
#16
Lucía Villarejo-López, Esperanza Jiménez, David Bartolomé-Martín, Francisco Zafra, Pablo Lapunzina, Carmen Aragón, Beatriz López-Corcuera
Glycinergic inhibitory neurons of the spinal dorsal horn exert critical control over the conduction of nociceptive signals to higher brain areas. The neuronal glycine transporter 2 (GlyT2) is involved in the recycling of synaptic glycine from the inhibitory synaptic cleft and its activity modulates intra and extracellular glycine concentrations. In this report we show that the stimulation of P2X purinergic receptors with βγ-methylene adenosine 5'-triphosphate induces the up-regulation of GlyT2 transport activity by increasing total and plasma membrane expression and reducing transporter ubiquitination...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28729062/pharmacological-activation-of-ampk-inhibits-incision-evoked-mechanical-hypersensitivity-and-the-development-of-hyperalgesic-priming-in-mice
#17
Michael D Burton, Dipti V Tillu, Khadijah Mazhar, Galo L Mejia, Marina N Asiedu, Kufreobong Inyang, Travis Hughes, Bo Lian, Gregory Dussor, Theodore J Price
New therapeutics to manage post-surgical pain are needed to mitigate the liabilities of opioid and other analgesics. Our previous work shows that key modulators of excitability in peripheral nociceptors, such as extracellular signal-regulated kinases (ERK) are inhibited by activation of adenosine monophosphate activated protein kinase (AMPK). We hypothesized that AMPK activation would attenuate acute incision-evoked mechanical hypersensitivity and the development of hyperalgesic priming caused by surgery in mice...
September 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28685530/early-and-late-behavioral-changes-in-sciatic-nerve-injury-may-be-modulated-by-nerve-growth-factor-and-substance-p-in-rats-a-chronic-constriction-injury-long-term-evaluation
#18
J T Da Silva, B G Evangelista, R A G Venega, M E Oliveira, M Chacur
Chronic constriction injury (CCI) simulates the symptoms of chronic nerve compression, which is characterized by allodynia and hyperalgesia. Nerve growth factor (NGF) is released after nerve injury by immune and Schwann cells and transported in retrograde fashion to the dorsal root ganglion (DRG), resulting in increased synthesis of Substance P (SP) and the triggering of neuropathic pain. Here we performed long-term evaluation of allodynia and hyperalgesia in a CCI model, and evaluated the effects of NGF and SP on the peripheral and central nervous systems...
April 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28676344/crispr-epigenome-editing-of-akap150-in-drg-neurons-abolishes-degenerative-ivd-induced-neuronal-activation
#19
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...
September 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28638341/herbal-medicine-ac591-prevents-oxaliplatin-induced-peripheral-neuropathy-in-animal-model-and-cancer-patients
#20
Xiaolan Cheng, Jiege Huo, Dawei Wang, Xueting Cai, Xiaoyan Sun, Wuguang Lu, Yang Yang, Chunping Hu, Xiaoning Wang, Peng Cao
Oxaliplatin is clinically compelling because of severe peripheral neuropathy. The side effect can result in dosage reductions or even cessation of chemotherapy, and no effective treatments are available. AC591 is a standardized extract of Huangqi Guizhi Wuwu decoction, an herbal formula recorded in "Synopsis of the Golden Chamber" for improving limb numbness and pain. In this study, we investigated whether AC591 could protect against oxaliplatin-induced peripheral neuropathy. To clarify it, a rat model of oxaliplatin-induced peripheral neuropathy was established, and neuroprotective effect of AC591 was studied...
2017: Frontiers in Pharmacology
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