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https://www.readbyqxmd.com/read/28636944/transduction-of-repetitive-mechanical-stimuli-by-piezo1-and-piezo2-ion-channels
#1
Amanda H Lewis, Alisa F Cui, Malcolm F McDonald, Jörg Grandl
Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28634208/ligand-and-voltage-gated-ca-2-channels-differentially-regulate-the-mode-of-vesicular-neuropeptide-release-in-mammalian-sensory-neurons
#2
Yeshi Wang, Qihui Wu, Meiqin Hu, Bin Liu, Zuying Chai, Rong Huang, Yuan Wang, Huadong Xu, Li Zhou, Lianghong Zheng, Changhe Wang, Zhuan Zhou
Neuropeptides released from dorsal root ganglion (DRG) neurons play essential roles in the neurotransmission of sensory inputs, including those underlying nociception and pathological pain. Neuropeptides are released from intracellular vesicles through two modes: a partial release mode called "kiss-and-run" (KAR) and a full release mode called "full fusion-like" (FFL). Using total internal reflection fluorescence (TIRF) microscopy, we traced the release of pH-sensitive green fluorescent protein-tagged neuropeptide Y (pHluorin-NPY) from individual dense-core vesicles in the soma and axon of single DRG neurons after Ca(2+) influx through either voltage-gated Ca(2+) channels (VGCCs) or ligand-gated transient receptor potential vanilloid 1 (TRPV1) channels...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28630356/developmental-downregulation-of-lis1-expression-limits-axonal-extension-and-allows-axon-pruning
#3
Kanako Kumamoto, Tokuichi Iguchi, Ryuichi Ishida, Takuya Uemura, Makoto Sato, Shinji Hirotsune
The robust axonal growth and regenerative capacities of young neurons decrease substantially with age. This developmental downregulation of axonal growth may facilitate axonal pruning and neural circuit formation but limits functional recovery following nerve damage. While external factors influencing axonal growth have been extensively investigated, relatively little is known about the intrinsic molecular changes underlying the age-dependent reduction in regeneration capacity. We report that developmental downregulation of LIS1 is responsible for the decreased axonal extension capacity of mature dorsal root ganglion (DRG) neurons...
June 19, 2017: Biology Open
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#4
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
#5
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/28615337/accumulation-of-methylglyoxal-increases-the-advanced-glycation-end-products-levels-in-drg-and-contributes-to-lumbar-disc-herniation-induced-persistent-pain
#6
Cui-Cui Liu, Xin-Sheng Zhang, Yu-Ting Ruan, Zhu-Xi Huang, Su-Bo Zhang, Meng Liu, Hai-Jie Luo, Shao-Ling Wu, Chao Ma
Lumbar disc herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia and increased MG level in plasma and dorsal root ganglion (DRG) and enhanced the excitability of small DRG neurons (< 30μm in diameter)...
June 14, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28614186/mir-34c-5p-functions-as-pronociceptive-microrna-in-cancer-pain-by-targeting-cav2-3-containing-calcium-channels
#7
Jagadeesh Gandla, Santosh Kumar Lomada, Jianning Lu, Rohini Kuner, Kiran Kumar Bali
Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs are a class of non-coding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for microRNAs regulated in dorsal root ganglia (DRG) neurons in a mouse model of bone metastatic pain, we identified miR-34c-5p as a functionally important pronociceptive microRNA. Despite these functional insights and therapeutic potential for miR-34c-5p, its molecular mechanism of action in peripheral sensory neurons remains unknown...
June 9, 2017: Pain
https://www.readbyqxmd.com/read/28612318/somatosensory-neuron-typing-with-high-coverage-single-cell-rna-sequencing-and-functional-analysis
#8
REVIEW
Changlin Li, Sashuang Wang, Yan Chen, Xu Zhang
Different physical and chemical stimuli are detected by the peripheral sensory receptors of dorsal root ganglion (DRG) neurons, and the generated inputs are transmitted via afferent fibers into the central nervous system. The gene expression profiles of DRG neurons contribute to the generation, transmission, and regulation of various somatosensory signals. Recently, the single-cell transcriptomes, cell types, and functional annotations of somatosensory neurons have been studied. In this review, we introduce our classification of DRG neurons based on single-cell RNA-sequencing and functional analyses, and discuss the technical approaches...
June 13, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28609318/biochemical-and-pharmacological-characterization-of-a-mice-model-of-complex-regional-pain-syndrome
#9
Vaskar Das, Jeffrey S Kroin, Mario Moric, Asokumar Buvanendran
BACKGROUND AND OBJECTIVES: Complex regional pain syndrome is a challenging disease to treat. Recently, a mouse fracture model of complex regional pain syndrome has been developed that has many signs of the clinical syndrome. However, many aspects of the sensory neuron biochemistry and behavioral and pharmacological characterization of this model remain to be clarified. METHODS: Mice were randomly assigned to fracture/cast or control (naive) groups. Fracture/cast mice underwent a closed distal tibia facture, with hindlimb wrapped in casting tape for 3 weeks...
July 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28600329/effect-of-electroacupuncture-on-thermal-pain-threshold-and-expression-of-calcitonin-gene-related-peptide-substance-p-and-%C3%AE-aminobutyric-acid-in-the-cervical-dorsal-root-ganglion-of-rats-with-incisional-neck-pain
#10
Li-Na Qiao, Jun-Ling Liu, Lian-Hong Tan, Hai-Long Yang, Xu Zhai, Yong-Sheng Yang
OBJECTIVE: Acupuncture therapy effectively reduces post-surgical pain, but its mechanism of action remains unclear. The aim of this study was to investigate whether expression of γ-aminobutyric acid (GABA) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the primary sensory neurons of cervical dorsal root ganglia (DRG) are involved in electroacupuncture (EA)-induced analgesia in a rat model of incisional neck pain. METHODS: The pain model was established by making a longitudinal midline neck incision in 60 rats...
June 9, 2017: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/28587873/regulation-of-transient-receptor-potential-cation-channel-subfamily-v1-protein-synthesis-by-the-phosphoinositide-3-kinase-akt-pathway-in-colonic-hypersensitivity
#11
Shanwei Shen, Hamad W Al-Thumairy, Fiza Hashmi, Li-Ya Qiao
The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor or vanilloid receptor 1 (VR1), is expressed in nociceptive neurons in the dorsal root ganglia (DRG) and participates in the transmission of pain. The present study investigated the underlying molecular mechanisms by which TRPV1 was regulated by nerve growth factor (NGF) signaling pathways in colonic hypersensitivity in response to colitis. We found that during colitis TRPV1 protein levels were significantly increased in specifically labeled colonic afferent neurons in both L1 and S1 DRGs...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28579544/could-clinical-photochemical-internalisation-be-optimised-to-avoid-neuronal-toxicity
#12
Caitriona O'Rourke, Colin Hopper, Alexander J MacRobert, James B Phillips, Josephine H Woodhams
Photochemical Internalisation (PCI) is a novel drug delivery technology in which low dose photodynamic therapy (PDT) can selectively rupture endo/lysosomes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release in the treatment of cancer. For PCI to be developed further, it is important to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to PCI treatment in a 3D co-culture system following incubation with photosensitisers: meso-tetraphenylporphine (TPPS2a) or tetraphenylchlorin disulfonate (TPCS2a) and Bleomycin...
June 1, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28575952/biocompatibility-and-neurotoxicity-of-magnesium-alloys-potentially-used-for-neural-repairs
#13
Jianjun Fei, Xiaoxiao Wen, Xiao Lin, Saijilafu, Weihua Wang, Olga Ren, Xinjian Chen, Lili Tan, Ke Yang, Huilin Yang, Lei Yang
Nerve injury, especially the large-size nerve damage, is a serious problem affecting millions of people. Entubulation of two ends of the injured nerve by using an implantable device, e.g., nerve guidance conduit (NGC), to guide the regeneration of nerve tissue is a promising approach for treating the large-size nerve defect. Magnesium (Mg) and its alloys are biodegradable, conductive, and own good mechanical properties. Mg(2+) ion, one of the main degradation products of Mg and its alloys, was reported to promote the proliferation of neural stem cells and their neurite production...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28569571/curcumin-inhibits-oxidative-stress-induced-trpm2-channel-activation-calcium-ion-entry-and-apoptosis-values-in-sh-sy5y-neuroblastoma-cells-involvement-of-transfection-procedure
#14
Ahmi Öz, Ömer Çelik
Transient Receptor Potential (TRP) channels are mostly Ca(2+) permeable cation channels. Transient Receptor Potential Melastatin-like 2 (TRPM2) is expressed in neurological tissues such as brain, dorsal root ganglia (DRG) neurons, hippocampus and also liver, heart and kidney. The SH-SY5Y cells are mostly used as a cellular model of neurodegenerative diseases, Alzheimer's and Parkinson's diseases. Curcumin, shows phenolic structure, synthesized by Curcuma longa L. (turmeric), has powerful non-enzymatically antioxidant effects compared with Vitamin E...
June 1, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/28558976/chronic-exposure-to-tumor-necrosis-factor-in-vivo-induces-hyperalgesia-upregulates-sodium-channel-gene-expression-and-alters-the-cellular-electrophysiology-of-dorsal-root-ganglion-neurons
#15
Bradford D Fischer, Cojen Ho, Igor Kuzin, Andrea Bottaro, Michael E O'Leary
The goal of these studies was to investigate the links between chronic exposure to the pro-inflammatory cytokine tumor necrosis factor (TNF), hyperalgesia and the excitability of dorsal root ganglion (DRG) sensory neurons. We employed transgenic mice that constitutively express TNF (TNFtg mice), a well-established model of chronic systemic inflammation. At 6 months of age, TNFtg mice demonstrated increased sensitivity to both mechanical and thermal heat stimulation relative to aged-matched wild-type controls...
May 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28556533/in-vitro-evaluation-of-gel-encapsulated-adipose-derived-stem-cells-biochemical-cues-for-in-vivo-peripheral-nerve-repair
#16
A C de Luca, C M Fonta, W Raffoul, P G di Summa, S P Lacour
Adipose-derived stem cells (ASC) are becoming one of the most exploited cells in peripheral nerve repair. They are fast-growing and able to protect neurons from apoptosis; they can reduce post-injury latency, and the risk of muscle atrophy. This study evaluates laminin-loaded fibrin gel as an ASC-carrying scaffold for nerve repair. In vitro, ASC retained their proliferative activity, but showed significant increase in proliferation rate when encapsulated in gels with low laminin concentrations (i.e. 1μg/mL)...
May 26, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28553323/phosphatidylserine-improves-axonal-transport-by-inhibition-of-hdac-and-has-potential-in-treatment-of-neurodegenerative-diseases
#17
REVIEW
Shiran Naftelberg, Gil Ast, Eran Perlson
Familial dysautonomia (FD) is a rare children neurodegenerative disease caused due to a point mutation in the IKBKAP gene that results in decreased IKK complex-associated protein (IKAP) protein production. The disease affects mostly the dorsal root ganglion (DRG) and the sympathetic ganglion. Recently, we found that the molecular mechanisms underlying neurodegeneration in FD patients are defects in axonal transport of nerve growth factors and microtubule stability in the DRG. Neurons are highly polarized cells with very long axons...
April 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28550532/drug-induced-hsp90-inhibition-alleviates-pain-in-monoarthritic-rats-and-alters-the-expression-of-new-putative-pain-players-at-the-drg
#18
Diana Sofia Marques Nascimento, Catarina Soares Potes, Miguel Luz Soares, António Carlos Ferreira, Marzia Malcangio, José Manuel Castro-Lopes, Fani Lourença Moreira Neto
Purinergic receptors (P2XRs) have been widely associated with pain states mostly due to their involvement in neuron-glia communication. Interestingly, we have previously shown that satellite glial cells (SGC), surrounding dorsal root ganglia (DRG) neurons, become activated and proliferate during monoarthritis (MA) in the rat. Here, we demonstrate that P2X7R expression increases in ipsilateral DRG after 1 week of disease, while P2X3R immunoreactivity decreases. We have also reported a significant induction of the activating transcriptional factor 3 (ATF3) in MA...
May 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28547032/car8-dorsal-root-ganglion-expression-and-genetic-regulation-of-analgesic-responses-are-associated-with-a-cis-eqtl-in-mice
#19
Roy C Levitt, Gerald Y Zhuang, Yuan Kang, Diana M Erasso, Udita Upadhyay, Mehtap Ozdemir, Eugene S Fu, Konstantinos D Sarantopoulos, Shad B Smith, William Maixner, Luda Diatchenko, Eden R Martin, Tim Wiltshire
Carbonic anhydrase-8 (Car8 mouse gene symbol) is devoid of enzymatic activity, but instead functions as an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1) to regulate this intracellular calcium release channel important in synaptic functions and neuronal excitability. Causative mutations in ITPR1 and carbonic anhydrase-8 in mice and humans are associated with certain subtypes of spinal cerebellar ataxia (SCA). SCA mice are genetically deficient in dorsal root ganglia (DRG) Car8 expression and display mechanical and thermal hypersensitivity and susceptibility to subacute and chronic inflammatory pain behaviors...
May 25, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28545921/a-mechanically-activated-ion-channel-is-functionally-expressed-in-the-mrgprb4-positive-sensory-neurons-which-detect-stroking-of-hairy-skin-in-mice
#20
Soichiro Yamaguchi, Ken-Ichi Otsuguro
Mas-related G-protein coupled receptor B4 (MrgprB4) has been reported to be expressed in the dorsal root ganglion (DRG) neurons which detect stroking of hairy skin of mice. However, the mechanisms by which the MrgprB4 positive (+) neurons respond to adequate stimulus remain unsolved as it was also reported that electrophysiological analysis of cultured MrgprB4+ neurons did not reveal responses to mechanical stimuli. Contrary to the observation, however, in this study we show that the MrgprB4+ neurons functionally express a mechanically activated channel using DRG neurons dissociated from genetically-modified mice whose MrgprB4+ neurons express a red fluorescent protein...
May 22, 2017: Neuroscience Letters
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