scholarly journals Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 320 ◽  
Author(s):  
Jennifer Cohnen ◽  
Lisa Kornstädt ◽  
Lisa Hahnefeld ◽  
Nerea Ferreiros ◽  
Sandra Pierre ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Neuronal Damage ◽  
Physical Contact ◽  
Melanoma Tumor ◽  
Inflammatory Processes ◽  
Sciatic Nerves ◽  
Tumor Types ◽  
Junction Proteins ◽  
Time Point

Cancer-induced pain occurs frequently in patients when tumors or their metastases grow in the proximity of nerves. Although this cancer-induced pain states poses an important therapeutical problem, the underlying pathomechanisms are not understood. Here, we implanted adenocarcinoma, fibrosarcoma and melanoma tumor cells in proximity of the sciatic nerve. All three tumor types caused mechanical hypersensitivity, thermal hyposensitivity and neuronal damage. Surprisingly the onset of the hypersensitivity was independent of physical contact of the nerve with the tumors and did not depend on infiltration of cancer cells in the sciatic nerve. However, macrophages and dendritic cells appeared on the outside of the sciatic nerves with the onset of the hypersensitivity. At the same time point downregulation of perineural tight junction proteins was observed, which was later followed by the appearance of microlesions. Fitting to the changes in the epi-/perineurium, a dramatic decrease of triglycerides and acylcarnitines in the sciatic nerves as well as an altered localization and appearance of epineural adipocytes was seen. In summary, the data show an inflammation at the sciatic nerves as well as an increased perineural and epineural permeability. Thus, interventions aiming to suppress inflammatory processes at the sciatic nerve or preserving peri- and epineural integrity may present new approaches for the treatment of tumor-induced pain.

scholarly journals Netrin-1 as a Multitarget Barrier Stabilizer in the Peripheral Nerve after Injury

2021 ◽  
Vol 22 (18) ◽  
pp. 10090
Author(s):  
Jeremy Tsung-Chieh Chen ◽  
Lea Schmidt ◽  
Christina Schürger ◽  
Mohammed K. Hankir ◽  
Susanne M. Krug ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Chronic Constriction Injury ◽  
Neuronal Damage ◽  
Pain Processing ◽  
Central Nervous Systems ◽  
Neuronal Guidance ◽  
Junction Proteins

The blood–nerve barrier and myelin barrier normally shield peripheral nerves from potentially harmful insults. They are broken down during nerve injury, which contributes to neuronal damage. Netrin-1 is a neuronal guidance protein with various established functions in the peripheral and central nervous systems; however, its role in regulating barrier integrity and pain processing after nerve injury is poorly understood. Here, we show that chronic constriction injury (CCI) in Wistar rats reduced netrin-1 protein and the netrin-1 receptor neogenin-1 (Neo1) in the sciatic nerve. Replacement of netrin-1 via systemic or local administration of the recombinant protein rescued injury-induced nociceptive hypersensitivity. This was prevented by siRNA-mediated knockdown of Neo1 in the sciatic nerve. Mechanistically, netrin-1 restored endothelial and myelin, but not perineural, barrier function as measured by fluorescent dye or fibrinogen penetration. Netrin-1 also reversed the decline in the tight junction proteins claudin-5 and claudin-19 in the sciatic nerve caused by CCI. Our findings emphasize the role of the endothelial and myelin barriers in pain processing after nerve damage and reveal that exogenous netrin-1 restores their function to mitigate CCI-induced hypersensitivity via Neo1. The netrin-1-neogenin-1 signaling pathway may thus represent a multi-target barrier protector for the treatment of neuropathic pain.

Prevention of painful neuromas by oblique transection of peripheral nerves

2006 ◽  
Vol 104 (2) ◽  
pp. 285-289 ◽  
Author(s):  
Wieslaw Marcol ◽  
Katarzyna Kotulska ◽  
Magdalena Larysz-Brysz ◽  
Grazyna Bierzyñska-Macyszyn ◽  
Pawel Wlaszczuk ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Traditional Method ◽  
Healing Process ◽  
Nerve Transection ◽  
Proximal Stump ◽  
Sciatic Nerves ◽  
Neuroma Formation

Object Neuroma formation often occurs at the proximal stump of the transected nerve, complicating the healing process after gap injuries or nerve biopsies. Most such neuromas cause therapy-resistant neuropathic pain. The purpose of this study was to determine whether oblique transection of the proximal stump of the sciatic nerve can prevent neuroma formation. Methods The sciatic nerves of 10 rats were transected unilaterally at an angle of 30°, and the peripheral segments of the nerves were removed. In 10 control animals the sciatic nerves were transected at a perpendicular angle. Twenty weeks after surgery the nerves were reexposed and collected. The presence of neuromas was determined by two board-certified pathologists on the basis of histopathological evaluations. Conclusions The oblique transection of peripheral nerves, contrary to perpendicularly transected nerves, is rarely followed by classic neuroma development. Moreover, neuropathic pain is significantly reduced compared with that following the traditional method of nerve transection.

Waterjet Dissection of Peripheral Nerves: An Experimental Study of the Sciatic Nerve of Rats

2010 ◽  
Vol 67 (suppl_2) ◽  
pp. ons368-ons376 ◽  
Author(s):  
Christoph A. Tschan ◽  
Doerthe Keiner ◽  
Harald D. Müller ◽  
Kerstin Schwabe ◽  
Michael R. Gaab ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerves ◽  
Scar Tissue ◽  
Small Water ◽  
Peripheral Nerve Surgery ◽  
Sciatic Nerves ◽  
Nerve Surgery ◽  
Waterjet Dissection

ABSTRACT BACKGROUND: Although waterjet dissection has been well evaluated in intracranial pathologies, little is known of its qualities in peripheral nerve surgery. Theoretically, the precise dissection qualities could support the separation of nerves from adjacent tissues and improve the preservation of nerve integrity in peripheral nerve surgery. OBJECTIVE: To evaluate the potential of the new waterjet dissector in peripheral nerve surgery. METHODS: Waterjet dissection with pressures of 20 to 80 bar was applied on the sciatic nerves of 101 rats. The effect of waterjet dissection on the sciatic nerve was evaluated by clinical tests, neurophysiological examinations, and histopathological studies up to 12 weeks after surgery. RESULTS: With waterjet pressures up to 30 bar, the sciatic nerve was preserved in its integrity in all cases. Functional damaging was observed at pressures of 40 bar and higher. However, all but 1 rat in the 80 bar subgroup showed complete functional regeneration at 12 weeks after surgery. Histopathologically, small water bubbles were observed around the nerves. At 40 bar and higher, the sciatic nerves showed signs of direct nerve injury. However, all these animals showed nerve regeneration after 12 weeks, as demonstrated by histological studies. CONCLUSION: Sciatic nerves were preserved functionally and morphologically at pressures up to 30 bar. Between 40 and 80 bar, reliable functional and morphological nerve regeneration occurred. Waterjet pressures up to 30 bar might be applied safely under clinical conditions. This technique might be well suited to separate intact peripheral nerves from adjacent tumor or scar tissue. Further studies will have to show the clinical relevance of these dissection qualities.

Arsenic-induced toxicity: effect on protein composition in sciatic nerve

2006 ◽  
Vol 25 (11) ◽  
pp. 667-674 ◽  
Author(s):  
A Vahidnia ◽  
F Romijn ◽  
M Tiller ◽  
G B van der Voet ◽  
F A de Wolff
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Protein Composition ◽  
Arsenic Compounds ◽  
Neurotoxic Effects ◽  
Electrophysiological Studies ◽  
Male Wistar Rats ◽  
Sciatic Nerves ◽  
L Proteins

Exposure to arsenic compounds may lead to skin and lung cancer and various disorders such as vascular disease and peripheral neuropathy in humans. Peripheral arsenic neurotoxicity has been demonstrated clinically and in electrophysiological studies. Patients intoxicated with arsenic show neurological symptoms in their feet and hands. These patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison with controls. The mechanism of arsenic peripheral nervous system (PNS) toxicity, however, has never been described before. This is the first study to investigate the toxicity of arsenic on the PNS. Male Wistar rats were exposed to arsenite given as a single dose i.v. After sacrifice, sciatic nerves were excised and the protein composition was analysed. Protein analysis of sciatic nerves showed disappearance of neurofilament and fibroblast proteins in rats treated with arsenite doses of 15 and 20 mg/kg in comparison with the control groups. Some fibroblast protein bands had disappeared in the 20-mg/kg dose group. The analysed neurofilament-M and-L proteins decreased dose dependency over time. arsenic affects the composition of proteins in the rat sciatic nerve, especially the neurofilaments. The reduction of signals in Western blot analysis reveals changes in cytoskeletal composition, which may well lead to neurotoxic effects in vivo.

Incorporation of Cholesterol into Peripheral Nerve Myelin

1972 ◽  
Vol 30 ◽  
pp. 334-335
Author(s):  
Frank A. Rawlins
Keyword(s):  
Electron Microscope ◽  
Sciatic Nerve ◽  
Electron Microscope Autoradiography ◽  
Myelin Sheaths ◽  
Microscope Autoradiography ◽  
Grain Distribution ◽  
Sciatic Nerves ◽  
Autoradiographic Analysis ◽  
Old Mice ◽  
Short Times

Several speculations exist as to the site of incorporation of preformed molecules into myelin. The possibility that an autoradiographic analysis of cholesterol-1,2-H3 incorporation at very short times after injection might shed some light in the solution of that problem led to the present experiment.Cholesterol-1,2-H3 was injected intraperitoneally into 24 tenday old mice. The animals were then sacrificed at 10,20,30,40,60,90,120 and 180 min after the injection and the sciatic nerves were processed for electron microscope autoradiography. To analyze the grain distribution in the autoradiograms of cross and longitudinal sections from each sciatic nerve myelin sheaths were subdivided into three compartments named: outer 1/3, middle 1/3 and inner 1/3 compartments.It was found that twenty min. after the injection of cholesterol -1.2-H3 (Figs. 1 and 2), 55% of the total number of grains (t.n.g) found in myelin were within the outer 1/3 compartment, 9% were within the middle 1/3 and 36% within the inner 1/3 compartment

Prevention and Healing of Calcium Signaling Mediated Neuronal Damage on successive Administration of Flavonoid Enriched Pterocarpus Marsupium Roxb in Peripheral Neuropathy Model

2020 ◽  
Vol 16 (9) ◽  
pp. 1346-1355
Author(s):  
Neethi Shaju ◽  
Mrinmoy Gautam ◽  
Abdul Khayum ◽  
Gunasekaran Venkatesh
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Motor Neurons ◽  
Neuronal Damage ◽  
Interleukin 10 ◽  
Central Mechanism ◽  
Behavioral Models ◽  
Cell Hyperplasia ◽  
Pterocarpus Marsupium

Background: Modern research on peripheral neuropathy circumstance utter that treatments with Vincristine (VCR) disturb the microtubular cells in sensory and motor neurons due to calcium over- load in sciatic nerve, unfortunately, VCR triggering the release of Tumor necrosis factor-α (TNFα) in central neurons causes excitotoxicity as well. Although ethnomedical information specifies that Pterocarpus marsupium Roxb (PM) is widely used for various nervous disorders, not yet justified on VCR induced peripheral neuropathy and in relation to central mechanism. Objective: This study is aimed to explore the possible central and peripheral mechanism of flavonoid enriched PM in VCR induced neuropathy model. Methods: Neuropathic pain was induced in female Wistar rats by VCR (75μg/ kg/day, i.p) for 10 days. Nociceptive thresholds were assessed by subjecting them to behavioral and biochemical estimation, proinflammatory cytokines along with morphological evaluation. Results: PM significantly increased the nociceptive threshold evident from various behavioral models in comparison to VCR group. More importantly, PM significantly reversed the VCR induced calcium elevation, glutamate and aspartate release in the brain. Discussion: It was also observed that the raised TNF-α, Interleukin-1β were controlled and interleukin- 10 was elevated in sciatic nerve after PM treatment. Evident from histology, PM markedly reversed the VCR induced axonal degeneration, Schwann cell hyperplasia, and myelin fibrosis. Conclusion: Flavonoid enriched PM both 100 & 200mg/kg post and co-administration exerted a preventive and curative effect in VCR induced neuropathic pain by controlling calcium-mediated excitotoxicity through peripheral and central mechanism.

On the issue of damage to the nerve trunks during intramuscular injections

1937 ◽  
Vol 33 (5) ◽  
pp. 590-596
Author(s):  
Sh. V. Bikchurin ◽  
E. I. Eselevich
Keyword(s):  
Sciatic Nerve ◽  
Injection Site ◽  
Peripheral Nerves ◽  
Intramuscular Injections

Cases of damage to the nerve trunks during intramuscular injections are now quite rare, since they can be avoided by strictly observing the rules for choosing the injection site. In the old manuals of Oppenheim and Lewandowski and in the newest manuals of Kraus and Brugsch (Toby Cohn), injections of various medications are indicated as the etiological moment of damage to the sciatic nerve. Injections of quinine and its compounds in the treatment of malaria, as well as injections of bioquinol, in some cases cause injury to peripheral nerves.

scholarly journals A Novel Model of Cancer-Induced Peripheral Neuropathy and the Role of TRPA1 in Pain Transduction

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Ahmad Maqboul ◽  
Bakheet Elsadek
Keyword(s):  
Immune Cells ◽  
Peripheral Nerves ◽  
Morphological Changes ◽  
Nerve Fibres ◽  
Cold Allodynia ◽  
Sciatic Nerves ◽  
Pain Transduction ◽  
Thermal Stimuli ◽  
Novel Model

Background. Models of cancer-induced neuropathy are designed by injecting cancer cells near the peripheral nerves. The interference of tissue-resident immune cells does not allow a direct contact with nerve fibres which affects the tumor microenvironment and the invasion process. Methods. Anaplastic tumor-1 (AT-1) cells were inoculated within the sciatic nerves (SNs) of male Copenhagen rats. Lumbar dorsal root ganglia (DRGs) and the SNs were collected on days 3, 7, 14, and 21. SN tissues were examined for morphological changes and DRG tissues for immunofluorescence, electrophoretic tendency, and mRNA quantification. Hypersensitivities to cold, mechanical, and thermal stimuli were determined. HC-030031, a selective TRPA1 antagonist, was used to treat cold allodynia. Results. Nociception thresholds were identified on day 6. Immunofluorescent micrographs showed overexpression of TRPA1 on days 7 and 14 and of CGRP on day 14 until day 21. Both TRPA1 and CGRP were coexpressed on the same cells. Immunoblots exhibited an increase in TRPA1 expression on day 14. TRPA1 mRNA underwent an increase on day 7 (normalized to 18S). Injection of HC-030031 transiently reversed the cold allodynia. Conclusion. A novel and a promising model of cancer-induced neuropathy was established, and the role of TRPA1 and CGRP in pain transduction was examined.

scholarly journals S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury

2008 ◽  
Vol 23 (6) ◽  
pp. 555-560 ◽  
Author(s):  
Tatiana Duobles ◽  
Thais de Sousa Lima ◽  
Beatriz de Freitas Azevedo Levy ◽  
Gerson Chadi
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Fibroblast Growth Factor ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Satellite Cells ◽  
Peripheral Nerves ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Cultured Schwann Cells

PURPOSE: The neurotrophic factor fibroblast growth factor-2 (FGF-2, bFGF) and Ca++ binding protein S100ß are expressed by the Schwann cells of the peripheral nerves and by the satellite cells of the dorsal root ganglia (DRG). Recent studies have pointed out the importance of the molecules in the paracrine mechanisms related to neuronal maintenance and plasticity of lesioned motor and sensory peripheral neurons. Moreover, cultured Schwann cells have been employed experimentally in the treatment of central nervous system lesions, in special the spinal cord injury, a procedure that triggers an enhanced sensorymotor function. Those cells have been proposed to repair long gap nerve injury. METHODS: Here we used double labeling immunohistochemistry and Western blot to better characterize in vitro and in vivo the presence of the proteins in the Schwann cells and in the satellite cells of the DRG as well as their regulation in those cells after a crush of the rat sciatic nerve. RESULTS: FGF-2 and S100ß are present in the Schwann cells of the sciatic nerve and in the satellite cells of the DRG. S100ß positive satellite cells showed increased size of the axotomized DRG and possessed elevated amount of FGF-2 immunoreactivity. Reactive satellite cells with increased FGF-2 labeling formed a ring-like structure surrounding DRG neuronal cell bodies.Reactive S100ß positive Schwann cells of proximal stump of axotomized sciatic nerve also expressed higher amounts of FGF-2. CONCLUSION: Reactive peripheral glial cells synthesizing FGF-2 and S100ß may be important in wound repair and restorative events in the lesioned peripheral nerves.

A Neuropathy in Goats Caused by Experimental Coyotillo (Karwinskia humboldtiana) Poisoning

1970 ◽  
Vol 7 (5) ◽  
pp. 420-434 ◽  
Author(s):  
K. M. Charlton ◽  
K. R. Pierce
Keyword(s):  
Electron Microscopy ◽  
Sciatic Nerve ◽  
Schwann Cells ◽  
Active Transport ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Light And Electron Microscopy ◽  
Segmental Demyelination ◽  
Femoral Site ◽  
Oral Doses

Lesions in peripheral nerves from 12 goats poisoned experimentally with coyotillo were studied by light and electron microscopy. The goats were poisoned with daily oral doses of the ground coyotillo fruits and killed at various times after the first day of dosing. Lesions at a mid-femoral site of the sciatic nerve included swelling of Schwann cells, degeneration of mitochondria, depletion of glycogen, splitting of myelin, segmental demyelination, and Wallerian degeneration. The results were suggestive of primary mitochondrial injury in Schwann cells with resultant impaired active transport, intracellular edema, splitting of myelin, and segmental demyelination.

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