Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves

Cohnen, Jennifer; Kornstädt, Lisa; Hahnefeld, Lisa; Ferreiròs, Nerea; Pierre, Sandra; Koehl, Ulrike; Deller, Thomas; Geißlinger, Gerd; Scholich, Klaus

doi:10.3390/cells9020320

Cited by 9 publications

(9 citation statements)

References 27 publications

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“…The claudin-1 antibody was raised against a synthetic peptide within human claudin-1 aa 150 to the C-terminus. The ab15098 antibody was used for targeting peripheral nerve perineurium ( Cohnen et al, 2020 ), as well as for applications of IHC of many other paraffin-embedded tissues [e.g., skin ( Kim et al, 2016 ), intestine ( Gumber et al, 2014 ; Mandle et al, 2019 ), and kidney ( Koda et al, 2014 )]; other claudin-1 antibodies were also used to label perineurium in peripheral nerves ( Pummi et al, 2004 ; Rittner et al, 2012 ; Piña et al, 2015 ; Reinhold et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat

et al. 2020

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It is necessary to understand the morphology of the vagus nerve (VN) to design and deliver effective and selective vagus nerve stimulation (VNS) because nerve morphology influences fiber responses to electrical stimulation. Specifically, nerve diameter (and thus, electrode-fiber distance), fascicle diameter, fascicular organization, and perineurium thickness all significantly affect the responses of nerve fibers to electrical signals delivered through a cuff electrode. We quantified the morphology of cervical and subdiaphragmatic VNs in humans, pigs, and rats: effective nerve diameter, number of fascicles, effective fascicle diameters, proportions of endoneurial, perineurial, and epineurial tissues, and perineurium thickness. The human and pig VNs were comparable sizes (∼2 mm cervically; ∼1.6 mm subdiaphragmatically), while the rat nerves were ten times smaller. The pig nerves had ten times more fascicles—and the fascicles were smaller—than in human nerves (47 vs. 7 fascicles cervically; 38 vs. 5 fascicles subdiaphragmatically). Comparing the cervical to the subdiaphragmatic VNs, the nerves and fascicles were larger at the cervical level for all species and there were more fascicles for pigs. Human morphology generally exhibited greater variability across samples than pigs and rats. A prior study of human somatic nerves indicated that the ratio of perineurium thickness to fascicle diameter was approximately constant across fascicle diameters. However, our data found thicker human and pig VN perineurium than those prior data: the VNs had thicker perineurium for larger fascicles and thicker perineurium normalized by fascicle diameter for smaller fascicles. Understanding these differences in VN morphology between preclinical models and the clinical target, as well as the variability across individuals of a species, is essential for designing suitable cuff electrodes and stimulation parameters and for informing translation of preclinical results to clinical application to advance the therapeutic efficacy of VNS.

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Section: Methodsmentioning

confidence: 99%

Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat

et al. 2020

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“…Dysfunction and breakage of the blood–spinal cord barrier is observed in several neurodegenerative disorders, peripheral neural injury-induced inflammatory pain, and chemotherapy-induced neuropathic pain [ 26 , 27 ]. In a rat sciatic nerve model, recruitment of inflammatory materials outside the nerve led to damage of the epineurium and depletion of epineural adipocytes [ 21 , 28 ]. Simultaneously, pro-nociceptive and pro-inflammatory mediators can enter the sciatic nerve through microlesions caused by neural damage [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…In a rat sciatic nerve model, recruitment of inflammatory materials outside the nerve led to damage of the epineurium and depletion of epineural adipocytes [ 21 , 28 ]. Simultaneously, pro-nociceptive and pro-inflammatory mediators can enter the sciatic nerve through microlesions caused by neural damage [ 28 ]. Therefore, non-myelinating Schwann cells may no longer protect non-myelinated neurons, causing tactile allodynia and loss of function of thermal sensitivity [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Simultaneously, pro-nociceptive and pro-inflammatory mediators can enter the sciatic nerve through microlesions caused by neural damage [ 28 ]. Therefore, non-myelinating Schwann cells may no longer protect non-myelinated neurons, causing tactile allodynia and loss of function of thermal sensitivity [ 28 ]. Transforaminal block is a valid procedure for the diagnosis and treatment of lumbosacral radicular pain, and acts by reducing inflammation and edema [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

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Predictive Value of the Phase Angle for Analgesic Efficacy in Lumbosacral Transforaminal Block

Kim

Park

Sim

et al. 2021

JCM

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The mechanism of low back and leg pain involves mixed neuropathic and nociceptive components. Spinal neuropathic pain is related to increased levels of inflammatory cytokines and disrupted and increased permeability of the blood–spinal cord barrier, originally composed of tight junctions of capillary endothelial cells surrounded by lamina. The phase angle (PA) estimates cell membrane integrity using bioelectrical impedance analysis. We evaluated the predictive value of the PA for analgesic efficacy in lumbosacral transforaminal block. We retrospectively collected data from 120 patients receiving transforaminal blocks for lumbosacral radicular pain and assessed the PA before and 5 min following the block. Responders (group R) and non-responders (group N) were defined by ≥50% and <50% pain reduction, respectively, on a numerical rating scale, 30 min following the block; clinical data and the PA were compared. Among the 109 included patients, 50 (45.9%) and 59 (54.1%) had ≥50% and <50% pain reduction, respectively. In group N, the PA change ratio showed 88.1% specificity, 32.0% sensitivity, and 62.4% accuracy; a ratio of <0.087 at 5 min following the block predicted non-response. A PA change ratio of <0.087 at 5 min following lumbar transforaminal blocks predicted non-responders with high specificity.

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“…A further lipidomic approach indicated the damage of neuronal myelin sheaths, decreased energy metabolism and the loss of epineural adipocytes which have an important protective role in peripheral nerves. The authors concluded that inhibition of inflammatory processes at the sciatic nerve or preserving peri- and epineural integrity might constitute suitable approaches to decrease tumor-induced pain [ 8 ].…”

mentioning

confidence: 99%

Novel Insights into Molecular Mechanisms of Chronic Pain

Niederberger

2020

Cells

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Pain is the most frequent cause triggering patients to visit a physician. The worldwide incidence of chronic pain is in the range of 20% of adults, and chronic pain conditions are frequently associated with several comorbidities and a drastic decrease in patients’ quality of life. Although several approved analgesics are available, such therapy is often not satisfying due to insufficient efficacy and/or severe side effects. Therefore, novel strategies for the development of safe and highly efficacious pain killers are urgently needed. To reach this goal, it is necessary to clarify the causes and signal transduction cascades underlying the onset and progression of the different types of chronic pain. The papers in this Special Issue cover a wide variety of mechanisms involved in different pain types such as inflammatory, neuropathic or cancer pain. Therefore, the results summarized here might contribute to a better understanding of the mechanisms in chronic pain and thereby to the development of novel therapeutic strategies for pain patients.

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Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves

Cited by 9 publications

References 27 publications

Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat

Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat

Predictive Value of the Phase Angle for Analgesic Efficacy in Lumbosacral Transforaminal Block

Novel Insights into Molecular Mechanisms of Chronic Pain

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