Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves

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

doi:10.3390/cells9020320

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Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves

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Institute of Clinical Pharmacology, University Hospital Goethe University Frankfurt, 60590 Frankfurt, Germany

Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD), 60596 Frankfurt/Main, Germany

Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, Germany

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Institute of Clinical Immunology, University of Leipzig, 04103 Leipzig City, Germany

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Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Neuroscience Center, Goethe-University Frankfurt, 60590 Frankfurt, Germany

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Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, 60596 Frankfurt/Main, Germany

Author to whom correspondence should be addressed.

Cells 2020, 9(2), 320; https://doi.org/10.3390/cells9020320

Received: 13 December 2019 / Revised: 23 January 2020 / Accepted: 25 January 2020 / Published: 29 January 2020

(This article belongs to the Special Issue Novel Insights into Molecular Mechanisms of Chronic Pain)

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Abstract

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. View Full-Text

Keywords: dendritic cells; macrophage; microlesions; perineurium; sciatic nerve; tumor pain

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MDPI and ACS Style

Cohnen, J.; Kornstädt, L.; Hahnefeld, L.; Ferreiros, N.; Pierre, S.; Koehl, U.; Deller, T.; Geisslinger, G.; Scholich, K. Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves. Cells 2020, 9, 320. https://doi.org/10.3390/cells9020320

AMA Style

Cohnen J, Kornstädt L, Hahnefeld L, Ferreiros N, Pierre S, Koehl U, Deller T, Geisslinger G, Scholich K. Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves. Cells. 2020; 9(2):320. https://doi.org/10.3390/cells9020320

Chicago/Turabian Style

Cohnen, Jennifer, Lisa Kornstädt, Lisa Hahnefeld, Nerea Ferreiros, Sandra Pierre, Ulrike Koehl, Thomas Deller, Gerd Geisslinger, and Klaus Scholich. 2020. "Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves" Cells 9, no. 2: 320. https://doi.org/10.3390/cells9020320

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Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves

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