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Ablation or modulation of the dorsal root ganglion

Tanziyah Muqeem, Biswarup Ghosh, Vitor Pinto, Angelo C Lepore, Manuel Covarrubias
Presynaptic voltage-gated K+ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Rafael Taeho Han, Han-Byul Kim, Young-Beom Kim, Kyungmin Choi, Gi Yeon Park, Pa Reum Lee, JaeHee Lee, Hye Young Kim, Chul-Kyu Park, Youngnam Kang, Seog Bae Oh, Heung Sik Na
Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by d(CH2 )5 [Tyr(Me)2 ,Dab5 ] AVP, a vasopressin-1a (V1a) receptor antagonist, but not by desGly-NH2 -d(CH2 )5 [DTyr2 , Thr4 ]OVT, an oxytocin receptor antagonist...
March 2018: Korean Journal of Physiology & Pharmacology
Priyanka Chauhan, Wen S Sheng, Shuxian Hu, Sujata Prasad, James R Lokensgard
BACKGROUND: Peripheral neuropathy is currently the most common neurological complication in HIV-infected individuals, occurring in 35-50% of patients undergoing combination anti-retroviral therapy. Data have shown that distal symmetric polyneuropathy develops in mice by 6 weeks following infection with the LP-BM5 retrovirus mixture. Previous work from our laboratory has demonstrated that glial cells modulate antiviral T-cell effector responses through the programmed death (PD)-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation...
March 5, 2018: Journal of Neuroinflammation
Yuanlong Song, Linlin Gao
The acutely dissociated neurons from the dorsal root ganglia (DRGs) are extensively used. The effects of acute dissociation on the properties of these neurons are, however, not clear. In this study, the action potentials (APs) were recorded from both acutely dissociated and in vivo identified DRG neurons with patch clamp and sharp electrode recording techniques, respectively. We found that acute dissociation slowed both the depolarizing and repolarizing rate of APs, and elongated the AP duration (APD). The lower recording temperature presented in the acutely dissociated neurons contributed to about 10% of these differences...
February 23, 2018: Somatosensory & Motor Research
Ramya Parameswaran, João L Carvalho-de-Souza, Yuanwen Jiang, Michael J Burke, John F Zimmerman, Kelliann Koehler, Andrew W Phillips, Jaeseok Yi, Erin J Adams, Francisco Bezanilla, Bozhi Tian
Optical methods for modulating cellular behaviour are promising for both fundamental and clinical applications. However, most available methods are either mechanically invasive, require genetic manipulation of target cells or cannot provide subcellular specificity. Here, we address all these issues by showing optical neuromodulation with free-standing coaxial p-type/intrinsic/n-type silicon nanowires. We reveal the presence of atomic gold on the nanowire surfaces, likely due to gold diffusion during the material growth...
February 19, 2018: Nature Nanotechnology
Basabjit Das, Melissa Conroy, David Moore, Joanne Lysaght, Connail McCrory
Radicular pain is a common cause of disability. Traditionally treatment has been either epidural steroid injection providing short-term relief or surgery with associated complications. Pulsed radiofrequency (PRF) applied to the Dorsal Root Ganglion (DRG) is a minimally invasive day-care treatment, which is gaining significant clinical acceptance in a selective group of patients with pure radicular pain. Greater insights into the immunomodulatory effects of this procedure may help to further optimise its application and find alternative treatment options...
February 16, 2018: Brain, Behavior, and Immunity
Mikie Hinata, Sunao Imai, Takao Sanaki, Junji Tsuchida, Takeshi Yoshioka, Kenichi Higashino, Miyuki Yamamoto, Masayuki Imai, Masahiko Soga, Narumi Horita, Isao Fukuda, Minoru Ikeda, Shoji Yamane, Atsushi Morita, Toshiyuki Kanemasa, Gaku Sakaguchi, Minoru Hasegawa, Masabumi Minami, Yasuhide Morioka
Transient receptor potential vanilloid 4 (TRPV4) receptor modulates pain, and this has been noted in several animal models. However, the involvement of TRPV4 in osteoarthritic (OA) pain remains poorly understood. The present study assessed the functional changes in TRPV4 and the expression of its endogenous ligand 5,6-epoxyeicosatrienoic acid (5,6-EET) in a rat monoiodoacetate (MIA)-induced OA pain model (MIA rats). MIA-treated rats showed reduced grip strength as compared with sham-treated rats, and this loss in function could be recovered by the intra-articular administration of a TRPV4 antagonist (HC067047 or GSK2193874)...
February 9, 2018: Pain
John M Dawes, Greg A Weir, Steven J Middleton, Ryan Patel, Kim I Chisholm, Philippa Pettingill, Liam J Peck, Joseph Sheridan, Akila Shakir, Leslie Jacobson, Maria Gutierrez-Mecinas, Jorge Galino, Jan Walcher, Johannes Kühnemund, Hannah Kuehn, Maria D Sanna, Bethan Lang, Alex J Clark, Andreas C Themistocleous, Noboru Iwagaki, Steven J West, Karolina Werynska, Liam Carroll, Teodora Trendafilova, David A Menassa, Maria Pia Giannoccaro, Ester Coutinho, Ilaria Cervellini, Damini Tewari, Camilla Buckley, M Isabel Leite, Hendrik Wildner, Hanns Ulrich Zeilhofer, Elior Peles, Andrew J Todd, Stephen B McMahon, Anthony H Dickenson, Gary R Lewin, Angela Vincent, David L Bennett
Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2-/- ) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens...
February 1, 2018: Neuron
Koji Yoshie, Pradeep S Rajendran, Louis Massoud, OhJin Kwon, Vasudev Tadimeti, Siamak Salavatian, Jeffrey Laurence Ardell, Kalyanam Shivkumar, Olujimi A Ajijola
Afferent fibers expressing the vanilloid receptor 1 (VR1) channel are implicated in cardiac nociception, however, their role in modulating reflex responses to cardiac stress is not well-understood. We evaluated this role in Yorkshire pigs by percutaneous epicardial application of resiniferatoxin (RTX), a toxic activator of the VR1 channel, resulting in depletion of cardiac VR1-expressing afferents. Hemodynamics, epicardial activation recovery intervals (ARIs), and in vivo activity of stellate ganglion (SG) neurons (SGNs) were recorded in control and RTX-treated animals...
January 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Vladimir A Martínez-Rojas, Guadalupe García, Roxana Noriega-Navarro, Crystell G Guzmán-Priego, Jorge E Torres-López, Vinicio Granados-Soto, Janet Murbartián
Background: Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed by a subset of nociceptive neurons that acts as a multimodal receptor. Its activity contributes to modulate nociceptive transmission in acute inflammatory pain. However, the role of this channel in chronic pain has been less studied. The purpose of this study was to investigate the local peripheral and spinal participation of TRPA1 channels in formalin-induced long-lasting hypersensitivity...
2018: Journal of Pain Research
Ana C N Freitas, Steve Peigneur, Flávio H P Macedo, José E Menezes-Filho, Paul Millns, Liciane F Medeiros, Maria A Arruda, Jader Cruz, Nicholas D Holliday, Jan Tytgat, Gareth Hathway, Maria E de Lima
The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19 induces antinociception by activation of CB1, μ and δ opioid receptors. Since the peripheral and central antinociception induced by PnPP-19 involves opioid activation, the aim of this work was to identify whether this synthetic peptide could directly activate opioid receptors and investigate the subtype selectivity for μ-, δ- and/or κ-opioid receptors...
January 15, 2018: Toxins
Na-Xi Tian, Yu Xu, Jin-Yu Yang, Lu Li, Xiao-Hong Sun, Yun Wang, Ying Zhang
Potassium voltage-gated channel interacting protein 3 (KChIP3), also termed downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a multifunctional protein belonging to the neuronal calcium sensor (NCS) family. Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG) neurons, suggesting the potential role of KChIP3 in peripheral sensory processing. Herein, we show that KChIP3 colocalizes with transient receptor potential ion channel V1 (TRPV1), a critical molecule involved in peripheral sensitization during inflammatory pain...
February 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ji-An Yang, Jun-Min He, Jing-Min Lu, Li-Juan Ji
Neuropathic pain is a kind of pain caused by primary or secondary impairment or dysfunction of peripheral or central nervous system. Patients with neuropathic pain were often with poor clinical outcome. We screened the differentially expressed genes between sciatic nerve injury and dorsal root ganglion gene in the sham operation model. Microarray and the spared nerve injury module were used to explore the molecular mechanism of neuropathic pain by injuries and the differentially expressed genes (DEGs) were identified out...
January 13, 2018: Journal of Cellular Biochemistry
Si-Jian Huang, Jian-Qin Yan, Hui Luo, Lu-Yao Zhou, Jian-Gang Luo
BACKGROUND: Immune and inflammatory responses occurring in the spinal cord play a pivotal role in the progression of radicular pain caused by intervertebral disk herniation. Interleukin-33 (IL-33) orchestrates inflammatory responses in a wide range of inflammatory and autoimmune disorders of the nervous system. Thus, the purpose of this study is to investigate the expression of IL-33 and its receptor ST2 in the dorsal spinal cord and to elucidate whether the inhibition of spinal IL-33 expression significantly attenuates pain-related behaviors in rat models of noncompressive lumbar disc herniation...
January 12, 2018: Journal of Neuroinflammation
Yumi Matsushita, Miki Manabe, Naoki Kitamura, Izumi Shibuya
Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined...
2018: PloS One
Veera Ganesh Yerra, Anil Kumar Kalvala, Bhoomika Sherkhane, Aparna Areti, Ashutosh Kumar
Adenosine monophosphate activated protein kinase (AMPK) has been studied for its myriad metabolic and mitochondrial benefits in several chronic diseases. Recent studies have uncovered its therapeutic potential against mitochondrial dysfunction in cultured dorsal root ganglion (DRG) neurons isolated from streptozotocin (STZ) induced diabetic rats. The present study is aimed at evaluating the pharmacological efficacy of berberine (BRB), a natural AMPK activator against experimental diabetic neuropathy (DN) phenotype developed in STZ (55 mg/kg, i...
December 19, 2017: Neuropharmacology
Li-Liang Zhang, Li-Na Qi, Ze-Yu Yao
OBJECTIVE: To observe the expression mode and modulation effects of lncRNA-Paupar in the process of bupivacaine induced neurotoxicity. METHODS: Dorsal root ganglion (DRG) neurons were cultured and neurotoxicity model was produced on it. And the expression of lncRNA-Paupar was evaluated by qRT-PCR. Lnc-Paupar specific siRNA-P and random control group siRNA-C were constructed,200 nmol/L siRNA-P,siRNA-C were transfected into ganglion cells and the apoptosis rate of transfected cells were observed by TUNEL method...
November 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Liangsheng Yu, Yuanxu Jiang, Bin Tang
PURPOSE: Lin-28 Homolog A gene (Lin28a) is an important regulator in nerve system. In this study, we investigated the functional mechanism of Lin28a during the process of bupivacaine (BUP)-induced neuronal apoptosis of spinal cord dorsal root ganglion neurons (DRGNs). METHODS: Young mouse DRGNs were cultured in vitro and treated with series concentrations of BUP. Apoptosis was evaluated by TUNEL assay. Corresponding Lin28a mRNA and protein expressions were evaluated by qRT-PCR and western blot (WB) assays...
December 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Chao-Jin Chen, De-Zhao Liu, Wei-Feng Yao, Yu Gu, Fei Huang, Zi-Qing Hei, Xiang Li
Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs) drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs) and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL) by using bioinformatic analysis...
2017: Journal of Pain Research
Anqi Sheng, Yan Zhang, Guang Li, Guangqin Zhang
Voltage-gated potassium (KV ) currents, subdivided into rapidly inactivating A-type currents (IA ) and slowly inactivating delayed rectifier currents (IK ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on KV currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited IA and IK in concentration-dependent manner...
February 2018: Neurochemical Research
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