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Ablation or modulation of the dorsal root ganglion

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https://www.readbyqxmd.com/read/28813592/3d-printed-phema-materials-for-topographical-and-biochemical-modulation-of-dorsal-root-ganglion-cell-response
#1
Adina Badea, Joselle M McCracken, Emily G Tillmaand, Mikhail Eugene 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 towards 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-ᴅ-lysine (PDL) to varying extents with peptides containing the integrin-binding motif Arg-Gly-Asp (RGD)...
August 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28751455/calcineurin-dysregulation-underlies-spinal-cord-injury-induced-k-channel-dysfunction-in-drg-neurons
#2
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 Sprague-Dawley female rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slows repolarization of the somatic action potential (AP) and attenuates the Kv3...
July 27, 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
#3
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
#4
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...
July 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
#5
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
#6
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/28638341/herbal-medicine-ac591-prevents-oxaliplatin-induced-peripheral-neuropathy-in-animal-model-and-cancer-patients
#7
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
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#8
REVIEW
Kaicheng Li, Bing Cai, Changlin Li, Xu Zhang
Noxious stimuli cause pain by activating cutaneous nociceptors. The Aδ- and C-fibers of dorsal root ganglion (DRG) neurons convey the nociceptive signals to the laminae I-II of spinal cord. In the dorsal horn of spinal cord, the excitatory afferent synaptic transmission is regulated by the inhibitory neurotransmitter γ-aminobutyric acid and modulators such as opioid peptides released from the spinal interneurons, and by serotonin, norepinepherine and dopamine from the descending inhibitory system. In contrast to the accumulated evidence for these central inhibitors and their neural circuits in the dorsal spinal cord, the knowledge about the endogenous suppressive mechanisms in nociceptive DRG neurons remains very limited...
June 15, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28623618/endothelin-1-decreases-excitability-of-the-dorsal-root-ganglion-neurons-via-etb-receptor
#9
Nandkishor K Mule, Jitendra N Singh, Kunal U Shah, Anil Gulati, Shyam S Sharma
Endothelin-1 (ET-1) has been demonstrated to be a pro-nociceptive as well as an anti-nociceptive agent. However, underlying molecular mechanisms for these pain modulatory actions remain unclear. In the present study, we evaluated the ability of ET-1 to alter the nociceptor excitability using a patch clamp technique in acutely dissociated rat dorsal root ganglion (DRG) neurons. ET-1 produced an increase in threshold current to evoke an action potential (I threshold) and hyperpolarization of resting membrane potential (RMP) indicating decreased excitability of DRG neurons...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28587505/chronic-cervical-radiculopathic-pain-is-associated-with-increased-excitability-and-hyperpolarization-activated-current-ih-in-large-diameter-dorsal-root-ganglion-neurons
#10
Da-Lu Liu, Xu Wang, Wen-Guang Chu, Na Lu, Wen-Juan Han, Yi-Kang Du, San-Jue Hu, Zhan-Tao Bai, Sheng-Xi Wu, Rou-Gang Xie, Ceng Luo
Cervical radiculopathic pain is a very common symptom that may occur with cervical spondylosis. Mechanical allodynia is often associated with cervical radiculopathic pain and is inadequately treated with current therapies. However, the precise mechanisms underlying cervical radiculopathic pain-associated mechanical allodynia have remained elusive. Compelling evidence from animal models suggests a role of large-diameter dorsal root ganglion neurons and plasticity of spinal circuitry attached with Aβ fibers in mediating neuropathic pain...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28581556/a-co-culture-microtunnel-technique-demonstrating-a-significant-contribution-of-unmyelinated-schwann-cells-to-the-acceleration-of-axonal-conduction-in-schwann-cell-regulated-peripheral-nerve-development
#11
Koji Sakai, Kenta Shimba, Kiyoshi Kotani, Yasuhiko Jimbo
Schwann cells (SCs) contribute to the regulation of axonal conduction in a myelin-dependent and -independent manner. However, due to the lack of investigative techniques that are able to record axonal conduction under conditions that control the proliferation of specific SC types, little is known about the extent to which myelinated SCs (mSCs) and unmyelinated SCs (umSCs) modulate axonal conduction. In this study, a microtunnel-electrode approach was applied to a neuron/SC co-culture technique. Rat dorsal root ganglion neurons and SCs were co-cultured in a microtunnel-electrode device, which enabled recording of the conduction delay in multiple axons passing through microtunnels...
August 14, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28575334/characterization-of-peripheral-and-central-sensitization-after-dorsal-root-ganglion-intervention-in-patients-with-unilateral-lumbosacral-radicular-pain-a-prospective-pilot-study
#12
V Mehta, S Snidvongs, B Ghai, R Langford, T Wodehouse
Background.: Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. Methods.: Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG...
June 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28565998/gabab-receptors-mediated-tonic-inhibition-of-glutamate-release-from-a%C3%AE-fibers-in-rat-laminae-iii-iv-of-the-spinal-cord-dorsal-horn
#13
Chiara Salio, Adalberto Merighi, Rita Bardoni
Presynaptic GABAB receptors (GABABRs) are highly expressed in dorsal root ganglion neurons and spinal cord dorsal horn. GABABRs located in superficial dorsal horn play an important antinociceptive role, by acting at both pre- and postsynaptic sites. GABABRs expressed in deep dorsal horn could be involved in the processing of touch sensation and possibly in the generation of tactile allodynia in chronic pain. The objective of this study was to characterize the morphological and functional properties of GABABRs expressed on Aβ fibers projecting to lamina III/IV and to understand their role in modulating excitatory synaptic transmission...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28533165/analgesic-conopeptides-targeting-g-protein-coupled-receptors-reduce-excitability-of-sensory-neurons
#14
REVIEW
Mahsa Sadeghi, Jeffrey R McArthur, Rocio K Finol-Urdaneta, David J Adams
Conotoxins (conopeptides) are a diverse group of peptides isolated from the venom of marine cone snails. Conus peptides modulate pain by interacting with voltage-gated ion channels and G protein-coupled receptors (GPCRs). Opiate drugs targeting GPCRs have long been used, nonetheless, many undesirable side effects associated with opiates have been observed including addiction. Consequently, alternative avenues to pain management are a largely unmet need. It has been shown that various voltage-gated calcium channels (VGCCs) respond to GPCR modulation...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28515697/trpa1-channels-modify-trpv1-mediated-current-responses-in-dorsal-root-ganglion-neurons
#15
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
#16
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/28505604/nrf2-and-nf-%C3%AE%C2%BAb-modulation-by-plumbagin-attenuates-functional-behavioural-and-biochemical-deficits-in-rat-model-of-neuropathic-pain
#17
Vijay Arruri, Prashanth Komirishetty, Aparna Areti, Siva Kumar Naik Dungavath, Ashutosh Kumar
BACKGROUND: Plumbagin is known to exhibit a broad range of biological activities including anti-cancer, antimicrobial and has been widely used traditionally. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) inhibitory and Nuclear factor (erythroid derived-2) like-2 (Nrf2) modulatory activities of Plumbagin have been reported already. In nerve injury model of neuropathy in rats, the role of NF-κB upregulation and declined antioxidant defence has been well recognized...
February 27, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28483977/uncoupling-of-unc5c-with-polymerized-tubb3-in-microtubules-mediates-netrin-1-repulsion
#18
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...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28446581/cl-channel-is-required-for-cxcl10-induced-neuronal-activation-and-itch-response-in-a-murine-model-of-allergic-contact-dermatitis
#19
Lintao Qu, Kai Fu, Steven G Shimada, Robert H LaMotte
Persistent itch often accompanies allergic contact dermatitis (ACD), but the underlying mechanisms remain largely unexplored. We previously demonstrated that CXCL10/CXCR3 signaling activated a subpopulation of cutaneous primary sensory neurons and mediated itch response after contact hypersensitivity (CHS), a murine model of ACD, induced by squaric acid dibutylester. The purpose of this study was to determine the ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch. In whole cell recordings, CXCL10 triggered a current in dorsal root ganglion (DRG) neurons innervating the area of CHS...
July 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28426962/evidence-for-mechanosensitive-channel-activity-of-tentonin-3-tmem150c
#20
Gyu-Sang Hong, Byeongjun Lee, Uhtaek Oh
Mechanosensation is essential for various physiological processes, and it is mediated by mechanotransduction channels. Recently, we reported that TMEM150C/Tentonin 3 (TTN3) confers mechanically activated currents with slow inactivation kinetics in several cell types, including dorsal root ganglion neurons (Hong et al., 2016). The accompanying Matters Arising by Dubin, Murthy, and colleagues confirms that naive heterologous cells demonstrate a mechanically activated current, but finds that this response is absent in CRISPR-Cas9 Piezo1 knockout cell lines and suggests that TTN3 is a modulator of Piezo1...
April 19, 2017: Neuron
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