scholarly journals Liver X Receptors Protect Dorsal Root Ganglia from Obesity-Induced Endoplasmic Reticulum Stress and Mechanical Allodynia

Cell Reports ◽  
2018 ◽  
Vol 25 (2) ◽  
pp. 271-277.e4 ◽  
Author(s):  
Chaitanya K. Gavini ◽  
Angie L. Bookout ◽  
Raiza Bonomo ◽  
Laurent Gautron ◽  
Syann Lee ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Liver X Receptors ◽  
X Receptors

scholarly journals Endoplasmic reticulum stress in the dorsal root ganglia regulates large‐conductance potassium channels and contributes to pain in a model of multiple sclerosis

2020 ◽  
Vol 34 (9) ◽  
pp. 12577-12598 ◽  
Author(s):  
Muhammad Saad Yousuf ◽  
Samira Samtleben ◽  
Shawn M. Lamothe ◽  
Timothy N. Friedman ◽  
Ana Catuneanu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Endoplasmic Reticulum ◽  
Potassium Channels ◽  
Endoplasmic Reticulum Stress ◽  
Dorsal Root Ganglia ◽  
Dorsal Root

Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

1986 ◽  
Vol 44 ◽  
pp. 368-369
Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Dorsal Root Ganglia ◽  
Rough Endoplasmic Reticulum ◽  
Dorsal Root ◽  
Vitamin B6 ◽  
Morphological Changes ◽  
Model System ◽  
Sensory Nerves ◽  
Peripheral Sensory

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

Time Course of Inflammation in Dorsal Root Ganglia Correlates with Differential Reversibility of Mechanical Allodynia

Neuroscience ◽  
2020 ◽  
Vol 428 ◽  
pp. 199-216 ◽  
Author(s):  
Myung-chul Noh ◽  
Benjamin Mikler ◽  
Twinkle Joy ◽  
Peter A. Smith
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Time Course

scholarly journals THE FINE STRUCTURE OF NEURONS

1955 ◽  
Vol 1 (1) ◽  
pp. 69-88 ◽  
Author(s):  
Sanford L. Palay ◽  
George E. Palade
Keyword(s):  
Endoplasmic Reticulum ◽  
Fine Structure ◽  
Electron Microscope ◽  
Cerebellar Cortex ◽  
Dorsal Root Ganglia ◽  
Medulla Oblongata ◽  
Dorsal Root ◽  
Thin Sections ◽  
Lipid Inclusions ◽  
Nissl Substance

1. Thin sections of representative neurons from intramural, sympathetic and dorsal root ganglia, medulla oblongata, and cerebellar cortex were studied with the aid of the electron microscope. 2. The Nissl substance of these neurons consists of masses of endoplasmic reticulum showing various degrees of orientation; upon and between the cisternae, tubules, and vesicles of the reticulum lie clusters of punctate granules, 10 to 30 mµ in diameter. 3. A second system of membranes can be distinguished from the endoplasmic reticulum of the Nissl bodies by shallower and more tightly packed cisternae and by absence of granules. Intermediate forms between the two membranous systems have been found. 4. The cytoplasm between Nissl bodies contains numerous mitochondria, rounded lipid inclusions, and fine filaments.

scholarly journals Depletion of Calcium Stores in Injured Sensory Neurons

2009 ◽  
Vol 111 (2) ◽  
pp. 393-405 ◽  
Author(s):  
Geza Gemes ◽  
Marcel Rigaud ◽  
Paul D. Weyker ◽  
Stephen E. Abram ◽  
Dorothee Weihrauch ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Spinal Nerve ◽  
Calcium Stores ◽  
Functional Importance ◽  
Electrophysiological Recordings ◽  
Intracellular Ca ◽  
Functional Consequences

Background Painful nerve injury leads to disrupted Ca signaling in primary sensory neurons, including decreased endoplasmic reticulum (ER) Ca storage. This study examines potential causes and functional consequences of Ca store limitation after injury. Methods Neurons were dissociated from axotomized fifth lumbar (L5) and the adjacent L4 dorsal root ganglia after L5 spinal nerve ligation that produced hyperalgesia, and they were compared to neurons from control animals. Intracellular Ca levels were measured with Fura-2 microfluorometry, and ER was labeled with probes or antibodies. Ultrastructural morphology was analyzed by electron microscopy of nondissociated dorsal root ganglia, and intracellular electrophysiological recordings were obtained from intact ganglia. Results Live neuron staining with BODIPY FL-X thapsigargin (Invitrogen, Carlsbad, CA) revealed a 40% decrease in sarco-endoplasmic reticulum Ca-ATPase binding in axotomized L5 neurons and a 34% decrease in L4 neurons. Immunocytochemical labeling for the ER Ca-binding protein calreticulin was unaffected by injury. Total length of ER profiles in electron micrographs was reduced by 53% in small axotomized L5 neurons, but it was increased in L4 neurons. Cisternal stacks of ER and aggregation of ribosomes occurred less frequently in axotomized neurons. Ca-induced Ca release, examined by microfluorometry with dantrolene, was eliminated in axotomized neurons. Pharmacologic blockade of Ca-induced Ca release with dantrolene produced hyperexcitability in control neurons, confirming its functional importance. Conclusions After axotomy, ER Ca stores are reduced by anatomic loss and possibly diminished sarco-endoplasmic reticulum Ca-ATPase. The resulting disruption of Ca-induced Ca release and protein synthesis may contribute to the generation of neuropathic pain.

scholarly journals Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats

2021 ◽  
Author(s):  
F.H.G. Ahlström ◽  
K. Mätlik ◽  
H. Viisanen ◽  
K.J. Blomqvist ◽  
X. Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Female Rats ◽  
Sexually Dimorphic ◽  
Spared Nerve Injury ◽  
Rna Seq

AbstractNeuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.

scholarly journals Local Sympathectomy Promotes Anti-inflammatory Responses and Relief of Paclitaxel-induced Mechanical and Cold Allodynia in Mice

2020 ◽  
Vol 132 (6) ◽  
pp. 1540-1553
Author(s):  
Raquel Tonello ◽  
Wenrui Xie ◽  
Sang Hoon Lee ◽  
Min Wang ◽  
Xiaojuan Liu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Growth Factor ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Sympathetic Blockade ◽  
Male Mice ◽  
Cold Allodynia

Abstract Background Patients undergoing cancer treatment often experience chemotherapy-induced neuropathic pain at their extremities, for which there is no U.S. Food and Drug Administration–approved drug. The authors hypothesized that local sympathetic blockade, which is used in the clinic to treat various pain conditions, can also be effective to treat chemotherapy-induced neuropathic pain. Methods A local sympathectomy (i.e., cutting the ipsilateral gray rami entering the spinal nerves near the L3 and L4 dorsal root ganglia) was performed in mice receiving intraperitoneal injections every other day of the chemotherapeutic drug paclitaxel. Sympathectomy effects were then assessed in chemotherapy-induced pain-like behaviors (i.e., mechanical and cold allodynia) and neuroimmune and electrophysiologic responses. Results Local microsympathectomy produced a fast recovery from mechanical allodynia (mean ± SD: sympathectomy vs. sham at day 5, 1.07 ± 0.34 g vs. 0.51 ± 0.17g, n = 5, P = 0.030 in male mice, and 1.08 ± 0.28 g vs. 0.62 ± 0.16 g, n = 5, P = 0.036 in female mice) and prevented the development of cold allodynia in both male and female mice after paclitaxel. Mechanistically, microsympathectomy induced transcriptional increases in dorsal root ganglia of macrophage markers and anti-inflammatory cytokines, such as the transforming growth factor-β. Accordingly, depletion of monocytes/macrophages and blockade of transforming growth factor-β signaling reversed the relief of mechanical allodynia by microsympathectomy. In particular, exogenous transforming growth factor-β was sufficient to relieve mechanical allodynia after paclitaxel (transforming growth factor-β 100 ng/site vs. vehicle at 3 h, 1.21 ± 0.34g vs. 0.53 ± 0.14 g, n = 5, P = 0.001 in male mice), and transforming growth factor-β signaling regulated neuronal activity in dorsal root ganglia. Conclusions Local sympathetic nerves control the progression of immune responses in dorsal root ganglia and pain-like behaviors in mice after paclitaxel, raising the possibility that clinical strategies already in use for local sympathetic blockade may also offer an effective treatment for patients experiencing chemotherapy-induced neuropathic pain. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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