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Ablation of the dorsal root ganglion

Brett Boonen, Yeranddy A Alpizar, Alicia Sanchez, Alejandro López-Requena, Thomas Voets, Karel Talavera
Acute neurogenic inflammation and pain associated to bacterial infection have been traditionally ascribed to sensitization and activation of sensory nerve afferents secondary to immune cell stimulation. However, we recently showed that lipopolysaccharides (LPS) directly activate the Transient Receptor Potential channels TRPA1 in sensory neurons and TRPV4 in airway epithelial cells. Here we investigated whether LPS activates other sensory TRP channels expressed in sensory neurons. Using intracellular Ca2+ imaging and patch-clamp we determined the effects of LPS on recombinant TRPV1, TRPV2, TRPM3 and TRPM8, heterologously expressed in HEK293T cells...
April 14, 2018: Cell Calcium
Mateus Fortes Rossato, Flavia Karine Rigo, Sara Marchesan Oliveira, Gustavo Petri Guerra, Cássia Regina Silva, Thiago Mattar Cunha, Marcus Vinícius Gomez, Juliano Ferreira, Gabriela Trevisan
The clinical use of paclitaxel as a chemotherapeutic agent is limited by the severe acute and chronic hypersensitivity caused when it is administered via intraperitoneal or intravenous routes. Thus far, evidence has suggested that transient receptor potential vanilloid-1 (TRPV1) has a key role in the chronic neuropathy induced by paclitaxel. Despite this, the role of TRPV1 in paclitaxel -related acute nociception, especially the development of visceral nociception, has not been evaluated. Thus, the goal of this study was to evaluate the participation of TRPV1 in a model of acute nociception induced by paclitaxel in rats and mice...
March 22, 2018: European Journal of Pharmacology
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 21, 2018: Neuron
Weitao Chen, Na Lu, Yue Ding, Yuan Wang, Leung Ting Chan, Xu Wang, Xin Gao, Songshan Jiang, Kai Liu
Neuronal mammalian target of rapamycin (mTOR) activity is a critical determinant of the intrinsic regenerative ability of mature neurons in the adult central nervous system (CNS). However, whether its action also applies to peripheral nervous system (PNS) neurons after injury remains elusive. To address this issue unambiguously, we used genetic approaches to determine the role of mTOR signaling in sensory axon regeneration in mice. We showed that deleting mTOR in dorsal root ganglion (DRG) neurons suppressed the axon regeneration induced by conditioning lesions...
November 2016: ENeuro
T Denton, J Howe, A Spalding
PURPOSE: Occipital neuralgia is a condition wherein pain is transmitted by the occipital nerves. Non-invasive therapies generally alleviate symptoms; however, persistent or recurring pain may require invasive procedures. Repeated invasive procedures upon failure are considered higher risk and are often contraindicated due to compounding inherent risk. SRS has not been explored as a treatment option largely due to the extracranial nature of the target (as opposed to the similar, more established trigeminal neuralgia), but advances in linear-accelerator frameless-based SRS now present an opportunity to evaluate the novel potential of this modality for this application...
June 2016: Medical Physics
Sean M O'Toole, Monica M Ferrer, Jennifer Mekonnen, Haihan Zhang, Yasuyuki Shima, David R Ladle, Sacha B Nelson
Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established...
March 1, 2017: Journal of Neurophysiology
Gyu-Sang Hong, Byeongjun Lee, Jungwon Wee, Hyeyeon Chun, Hyungsup Kim, Jooyoung Jung, Joo Young Cha, Tae-Ryong Riew, Gyu Hyun Kim, In-Beom Kim, Uhtaek Oh
Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics...
July 6, 2016: Neuron
Liong Liem, Eric van Dongen, Frank J Huygen, Peter Staats, Jeff Kramer
Chronic neuropathic pain is a widespread problem with negative personal and societal consequences. Despite considerable clinical neuroscience research, the goal of developing effective, reliable, and durable treatments has remained elusive. The critical role played by the dorsal root ganglion (DRG) in the induction and maintenance of chronic pain has been largely overlooked in these efforts, however. It may be that, by targeting this site, robust new options for pain management will be revealed. This review summarizes recent advances in the knowledge base for DRG-targeted treatments for neuropathic pain:• Pharmacological options including the chemical targeting of voltage-dependent calcium channels, transient receptor potential channels, neurotrophin production, potentiation of opioid transduction pathways, and excitatory glutamate receptors...
July 2016: Regional Anesthesia and Pain Medicine
Satoshi Fuseya, Katsumi Yamamoto, Hitoshi Minemura, Satoshi Yamaori, Tomoyuki Kawamata, Mikito Kawamata
BACKGROUND: The aim of this study was to determine whether systemic administration of QX-314 reduces bone cancer pain through selective inhibition of transient receptor potential vanilloid subfamily 1 (TRPV1)-expressing afferents. METHODS: A mouse model of bone cancer pain was used. The authors examined the effects of bolus (0.01 to 3 mg/kg, n = 6 to 10) and continuous (5 mg kg h, n = 5) administration of QX-314 on both bone cancer pain-related behaviors and phosphorylated cyclic adenosine monophosphate response element-binding protein expression in dorsal root ganglion neurons (n = 3 or 6) and the effects of ablation of TRPV1-expressing afferents on bone cancer pain-related behaviors (n = 10)...
July 2016: Anesthesiology
Erin G Reed-Geaghan, Margaret C Wright, Lauren A See, Peter C Adelman, Kuan Hsien Lee, H Richard Koerber, Stephen M Maricich
UNLABELLED: The extent to which the skin instructs peripheral somatosensory neuron maturation is unknown. We studied this question in Merkel cell-neurite complexes, where slowly adapting type I (SAI) neurons innervate skin-derived Merkel cells. Transgenic mice lacking Merkel cells had normal dorsal root ganglion (DRG) neuron numbers, but fewer DRG neurons expressed the SAI markers TrkB, TrkC, and Ret. Merkel cell ablation also decreased downstream TrkB signaling in DRGs, and altered the expression of genes associated with SAI development and function...
April 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Md Habibur Rahman, Mithilesh Kumar Jha, Jong-Heon Kim, Youngpyo Nam, Maan Gee Lee, Younghoon Go, Robert A Harris, Dong Ho Park, Hyun Kook, In-Kyu Lee, Kyoungho Suk
The dorsal root ganglion (DRG) is a highly vulnerable site in diabetic neuropathy. Under diabetic conditions, the DRG is subjected to tissue ischemia or lower ambient oxygen tension that leads to aberrant metabolic functions. Metabolic dysfunctions have been documented to play a crucial role in the pathogenesis of diverse pain hypersensitivities. However, the contribution of diabetes-induced metabolic dysfunctions in the DRG to the pathogenesis of painful diabetic neuropathy remains ill-explored. In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to painful diabetic neuropathy...
March 11, 2016: Journal of Biological Chemistry
Hiroshi Urabe, Tomoya Terashima, Hideto Kojima, Lawrence Chan
Diabetic peripheral neuropathy (DPN) is a major diabetic complication. Previously, we showed that hyperglycemia induces the appearance of proinsulin (PI)-producing bone marrow-derived cells (PI-BMDCs), which fuse with dorsal root ganglion neurons, causing apoptosis, nerve dysfunction, and DPN. In this study, we have devised a strategy to ablate PI-BMDCs in mice in vivo. The use of this strategy to selectively ablate TNFα-producing PI-BMDCs in diabetic mice protected these animals from developing DPN. The findings provide powerful validation for a pathogenic role of PI-BMDCs and identify PI-BMDCs as an accessible therapeutic target for the treatment and prevention of DPN...
February 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
Zhen-Zhong Xu, Yong Ho Kim, Sangsu Bang, Yi Zhang, Temugin Berta, Fan Wang, Seog Bae Oh, Ru-Rong Ji
Mechanical allodynia, induced by normally innocuous low-threshold mechanical stimulation, represents a cardinal feature of neuropathic pain. Blockade or ablation of high-threshold, small-diameter unmyelinated group C nerve fibers (C-fibers) has limited effects on mechanical allodynia. Although large, myelinated group A fibers, in particular Aβ-fibers, have previously been implicated in mechanical allodynia, an A-fiber-selective pharmacological blocker is still lacking. Here we report a new method for targeted silencing of A-fibers in neuropathic pain...
November 2015: Nature Medicine
Jun-Ho La, Bin Feng, Kaori Kaji, Erica S Schwartz, G F Gebhart
Isolectin B4-binding (IB4+) dorsal root ganglion (DRG) neurons are distinct from peptidergic DRG neurons in their terminal location in the spinal cord and respective contributions to various classes and modalities of nociception. In DRG neurons innervating the mouse colon (c-DRG neurons), the reported proportion of IB4+ population is inconsistent across studies, and little is known regarding their role in colorectal mechanonociception. To address these issues, in C57BL/6J mice, we quantified IB4+ binding after labeling c-DRG neurons with Fast Blue and examined functional consequences of ablating these neurons by IB4-conjugated saporin...
February 2016: Pain
R Bale
CLINICAL ISSUE: Increasing understanding of the anatomy and physiology of neural structures has led to the development of surgical and percutaneous neurodestructive methods in order to target and destroy various components of afferent nociceptive pathways. The dorsal root ganglia and in particular the ganglia of the autonomous nervous system are targets for radiological interventions. The autonomous nervous system is responsible for the regulation of organ functions, sweating, visceral and blood vessel-associated pain...
October 2015: Der Radiologe
Stefan R Pulver, Timothy G Bayley, Adam L Taylor, Jimena Berni, Michael Bate, Berthold Hedwig
We have established a preparation in larval Drosophila to monitor fictive locomotion simultaneously across abdominal and thoracic segments of the isolated CNS with genetically encoded Ca(2+) indicators. The Ca(2+) signals closely followed spiking activity measured electrophysiologically in nerve roots. Three motor patterns are analyzed. Two comprise waves of Ca(2+) signals that progress along the longitudinal body axis in a posterior-to-anterior or anterior-to-posterior direction. These waves had statistically indistinguishable intersegmental phase delays compared with segmental contractions during forward and backward crawling behavior, despite being ∼10 times slower...
November 2015: Journal of Neurophysiology
Jeffrey V Kras, Christine L Weisshaar, Parul S Pall, Beth A Winkelstein
Non-physiological stretch of the cervical facet joint's capsular ligament induces persistent behavioral hypersensitivity and spinal neuronal hyperexcitability via an intra-articular NGF-dependent mechanism. Although that ligament is innervated by nociceptors, it is unknown if a subpopulation is exclusively responsible for the behavioral and spinal neuronal responses to intra-articular NGF and/or facet joint injury. This study ablated joint afferents using the neurotoxin saporin targeted to neurons involved in either peptidergic ([Sar(9),Met (O2)(11)]-substance P-saporin (SSP-Sap)) or non-peptidergic (isolectin B4-saporin (IB4-Sap)) signaling to investigate the contributions of those neuronal populations to facet-mediated pain...
September 14, 2015: Neuroscience Letters
Jennifer L Beams, Matthew T Kline, Todd D Rozen
OBJECTIVE: The objective of this research is to describe novel procedural treatments for hemicrania continua that allow patients to remain off indomethacin. METHODS: Case reports are presented. RESULTS: We describe four distinct patients with indomethacin-responsive hemicrania continua who were unable to discontinue the use of indomethacin without headache recurrence. No other medications were effective for their syndrome. Secondary causes of headache were ruled out in each case...
November 2015: Cephalalgia: An International Journal of Headache
Jiashu Sun, Haitao Zhang
This paper was to analyze and contrast the damage rate on the thoracic segment different position of the dorsal root ganglion(dorsal root ganglion, DRG) caused by different puncture path in radiofrequency ablation, thus the best RF target way for the thoracic segment of different types of DRG was confirmed. According to the difference of puncture and ablation damage way, 14 segmental spinal specimens were randomly divided into three groups, and then conducted DRG radiofrequency damage on percutaneous puncture path according to the type of DRG position...
September 2014: Pakistan Journal of Pharmaceutical Sciences
Mayur Sharma, Andrew Shaw, Milind Deogaonkar
Complex craniofacial pain can be a challenging condition to manage both medically and surgically, but there is a resurgence of interest in the role of neurostimulation therapy. Surgical options for complex craniofacial pain syndromes include peripheral nerve/field stimulation, ganglion stimulation, spinal cord stimulation, dorsal nerve root entry zone lesioning, motor cortex stimulation, and deep brain stimulation. Peripheral nerve/field stimulation is rapidly being explored and is preferred by both patients and surgeons...
October 2014: Neurosurgery Clinics of North America
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