scholarly journals Surgical extraction of human dorsal root ganglia from organ donors and preparation of primary sensory neuron cultures

2016 ◽  
Vol 11 (10) ◽  
pp. 1877-1888 ◽  
Author(s):  
Manouela V Valtcheva ◽  
Bryan A Copits ◽  
Steve Davidson ◽  
Tayler D Sheahan ◽  
Melanie Y Pullen ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Organ Donors ◽  
Primary Sensory Neuron ◽  
Surgical Extraction

scholarly journals Enhanced T-type calcium channel 3.2 activity in sensory neurons contributes to neuropathic-like pain of monosodium iodoacetate-induced knee osteoarthritis

2020 ◽  
Vol 16 ◽  
pp. 174480692096380
Author(s):  
Seung Min Shin ◽  
Yongsong Cai ◽  
Brandon Itson-Zoske ◽  
Chensheng Qiu ◽  
Xu Hao ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Primary Sensory Neurons ◽  
Primary Sensory Neuron ◽  
Spinal Dorsal ◽  
Osteoarthritis Pain ◽  
Monosodium Iodoacetate

The monosodium iodoacetate knee osteoarthritis model has been widely used for the evaluation of osteoarthritis pain, but the pathogenesis of associated chronic pain is not fully understood. The T-type calcium channel 3.2 (CaV3.2) is abundantly expressed in the primary sensory neurons, in which it regulates neuronal excitability at both the somata and peripheral terminals and facilitates spontaneous neurotransmitter release at the spinal terminals. In this study, we investigated the involvement of primary sensory neuron-CaV3.2 activation in monosodium iodoacetate osteoarthritis pain. Knee joint osteoarthritis pain was induced by intra-articular injection of monosodium iodoacetate (2 mg) in rats, and sensory behavior was evaluated for 35 days. At that time, knee joint structural histology, primary sensory neuron injury, and inflammatory gliosis in lumbar dorsal root ganglia, and spinal dorsal horn were examined. Primary sensory neuron-T-type calcium channel current by patch-clamp recording and CaV3.2 expression by immunohistochemistry and immunoblots were determined. In a subset of animals, pain relief by CaV3.2 inhibition after delivery of CaV3.2 inhibitor TTA-P2 into sciatic nerve was investigated. Knee injection of monosodium iodoacetate resulted in osteoarthritis histopathology, weight-bearing asymmetry, sensory hypersensitivity of the ipsilateral hindpaw, and inflammatory gliosis in the ipsilateral dorsal root ganglia, sciatic nerve, and spinal dorsal horn. Neuronal injury marker ATF-3 was extensively upregulated in primary sensory neurons, suggesting that neuronal damage was beyond merely knee-innervating primary sensory neurons. T-type current in dissociated primary sensory neurons from lumbar dorsal root ganglia of monosodium iodoacetate rats was significantly increased, and CaV3.2 protein levels in the dorsal root ganglia and spinal dorsal horn ipsilateral to monosodium iodoacetate by immunoblots were significantly increased, compared to controls. Perineural application of TTA-P2 into the ipsilateral sciatic nerve alleviated mechanical hypersensitivity and weight-bearing asymmetry in monosodium iodoacetate osteoarthritis rats. Overall, our findings demonstrate an elevated CaV3.2 expression and enhanced function of primary sensory neuron-T channels in the monosodium iodoacetate osteoarthritis pain. Further study is needed to delineate the importance of dysfunctional primary sensory neuron-CaV3.2 in osteoarthritis pain.

scholarly journals Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia

2004 ◽  
Vol 229 (3) ◽  
pp. 618-629 ◽  
Author(s):  
Branden R. Nelson ◽  
Meru Sadhu ◽  
Jennifer C. Kasemeier ◽  
Lawrence W. Anderson ◽  
Frances Lefcort
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root

scholarly journals Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity

2021 ◽  
Vol 2 ◽  
Author(s):  
Zachary K. Ford ◽  
Ashlie N. Reker ◽  
Sisi Chen ◽  
Feni Kadakia ◽  
Alexander Bunk ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Cannabinoid Receptors ◽  
Calcium Influx ◽  
Membrane Properties ◽  
Neuron Activity ◽  
Membrane Excitability ◽  
Bidirectional Modulation

Cannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal root ganglia were rapidly recovered from organ donors to perform physiological and anatomical investigations into the potential for cannabinoids to mediate analgesia at the level of the peripheral nervous system. Anatomical characterization of in situ gene expression and immunoreactivity showed that 61 and 53% of human sensory neurons express the CB1 gene and receptor, respectively. Calcium influx evoked by the algogen capsaicin was measured by Fura-2AM in dissociated human sensory neurons pre-exposed to the inflammatory mediator prostaglandin E2 (PGE2) alone or together with CB13 (1 μM), a cannabinoid agonist with limited blood–brain barrier permeability. Both a higher proportion of neurons and a greater magnitude of response to capsaicin were observed after exposure to CB13, indicating cannabinoid-mediated sensitization. In contrast, membrane properties measured by patch-clamp electrophysiology demonstrated that CB13 suppressed excitability and reduced action potential discharge in PGE2-pre-incubated sensory neurons, suggesting the suppression of sensitization. This bidirectional modulation of sensory neuron activity suggests that cannabinoids may suppress overall membrane excitability while simultaneously enhancing responsivity to TRPV1-mediated stimuli. We conclude that peripherally restricted cannabinoids may have both pro- and anti-nociceptive effects in human sensory neurons.

scholarly journals Expression of huntingtin-associated protein 1 in adult mouse dorsal root ganglia and its neurochemical characterization in reference to sensory neuron subpopulations

IBRO Reports ◽  
2020 ◽  
Vol 9 ◽  
pp. 258-269 ◽  
Author(s):  
Md Nabiul Islam ◽  
Naoki Maeda ◽  
Emi Miyasato ◽  
Mir Rubayet Jahan ◽  
Abu Md Mamun Tarif ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Adult Mouse

scholarly journals A video protocol for rapid dissection of mouse dorsal root ganglia from defined spinal levels

2020 ◽  
Author(s):  
James Nicholas Sleigh ◽  
Steven J West ◽  
Giampietro Schiavo
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Genetic Diseases ◽  
Spinal Column ◽  
Spinal Cord Dorsal Horn ◽  
Neuron Development ◽  
Spinal Cord Dorsal ◽  
And Function ◽  
External Stimuli

Abstract Objective: Dorsal root ganglia (DRG) are heterogeneous assemblies of assorted sensory neuron cell bodies found in bilateral pairs at every level of the spinal column. Pseudounipolar afferent neurons convert external stimuli from the environment into electrical signals that are retrogradely transmitted to the spinal cord dorsal horn. To do this, they extend single axons from their DRG-resident somas that then bifurcate and project both centrally and distally. DRG can be dissected from mice at embryonic stages and any age post-natally, and have been extensively used to study sensory neuron development and function, response to injury, and pathological processes in acquired and genetic diseases. We have previously published a step-by-step dissection method for the rapid isolation of post-natal mouse DRG. Here, the objective is to extend the protocol by providing training videos that showcase the dissection in fine detail and permit the extraction of ganglia from defined spinal levels. Results: By following this method, the reader will be able to swiftly and accurately isolate specific lumbar, thoracic, and cervical DRG from mice. Dissected ganglia can then be used for RNA/protein analyses, subjected to immunohistochemical examination, and cultured as explants or dissociated primary neurons, for in-depth investigations of sensory neuron biology.

cAMP and cGMP Contribute to Sensory Neuron Hyperexcitability and Hyperalgesia in Rats With Dorsal Root Ganglia Compression

2006 ◽  
Vol 95 (1) ◽  
pp. 479-492 ◽  
Author(s):  
Xue-Jun Song ◽  
Zheng-Bei Wang ◽  
Qiang Gan ◽  
Edgar T. Walters
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Camp And Cgmp

scholarly journals Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study

2015 ◽  
Vol 114 (6) ◽  
pp. 3140-3153 ◽  
Author(s):  
Danielle Sundt ◽  
Nikita Gamper ◽  
David B. Jaffe
Keyword(s):  
Ion Channels ◽  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Major Type ◽  
Delayed Rectifier ◽  
Kcnq Channels ◽  
Voltage Gated ◽  
C Fibers ◽  
M Channels

Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na+ channels. A model containing only fast voltage-gated Na+ and delayed-rectifier K+ channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca2+-dependent K+ current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na+-K+ pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca2+-dependent K+ current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain.

scholarly journals p38 Mitogen–activated Protein Kinase Activation by Nerve Growth Factor in Primary Sensory Neurons Upregulates μ-Opioid Receptors to Enhance Opioid Responsiveness Toward Better Pain Control

2011 ◽  
Vol 114 (1) ◽  
pp. 150-161 ◽  
Author(s):  
Reine-Solange Yamdeu ◽  
Mohammed Shaqura ◽  
Shaaban A. Mousa ◽  
Michael Schäfer ◽  
Jana Droese
Keyword(s):  
Nerve Growth Factor ◽  
P38 Mapk ◽  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Mapk Inhibitors

Background Sensory neuron opioid receptors are targets for spinal, epidural, and peripheral opioid application. Although local nerve growth factor (NGF) has been identified as a mediator of sensory neuron μ-opioid receptor (MOR) up-regulation, the signaling pathways involved have not been yet identified. Methods Wistar rats were treated with intraplantar vehicle, Freund's complete adjuvant, NGF, NGF plus intrathecal p38 mitogen-activated protein kinase (MAPK) inhibitors, or NGF plus extracellular signal-regulated kinase-1/2 MAPK inhibitors. After 4 days of treatment, paw pressure thresholds of an intraplantar full (fentanyl) or partial (buprenorphine) opioid agonist were determined by algesiometry. Tissue samples from rat dorsal root ganglia were subjected to radiolabeled ligand binding, Western blot analysis, and confocal immunofluorescence. Results Exogenous and endogenous NGF resulting from Freund's complete adjuvant inflammation produced significant potentiation and enhanced efficacy in fentanyl- and buprenorphine-induced dose-dependent antinociception, respectively. Furthermore, in the ipsilateral dorsal root ganglia, NGF produced a significant increase in MOR binding sites, proteins, and immunoreactive neurons. In parallel, phosphorylated p38-MAPK protein, the number of phosphorylated p38-MAPK immunoreactive neurons expressing MOR in dorsal root ganglia, and the peripherally directed axonal transport of MOR significantly increased. Finally, NGF-induced effects occurring in dorsal root ganglia, on axonal transport, and on the potentiation or enhanced efficacy of opioid antinociception were abrogated by inhibition of p38, but not extracellular signal-regulated kinase-1/2, MAPK. Conclusions Local NGF through activation of the p38-MAPK pathway leads to adaptive changes in sensory neuron MOR toward enhanced susceptibility to local opioids. This effect may act as a counter-regulatory response to p38-MAPK-induced pain (e.g., inflammatory pain) to facilitate opioid-mediated antinociception.

scholarly journals Does the physical disector method provide an accurate estimation of sensory neuron number in rat dorsal root ganglia?

2009 ◽  
Vol 176 (2) ◽  
pp. 290-297 ◽  
Author(s):  
Sibylle Delaloye ◽  
Rudolf Kraftsik ◽  
Thierry Kuntzer ◽  
Ibtissam Barakat-Walter
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Accurate Estimation ◽  
Neuron Number ◽  
Physical Disector
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