Tumors provoke inflammation and perineural microlesions at adjacent peripheral nerves

  • 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.

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Metadaten
Author:Jennifer Cohnen, Lisa KornstädtGND, Lisa Hahnefeld, Nerea Ferreiros, Sandra Pierre, Ulrike Köhl, Thomas Deller, Gerd GeisslingerORCiDGND, Klaus Scholich
URN:urn:nbn:de:hebis:30:3-544287
DOI:https://doi.org/10.3390/cells9020320
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/32013137
Parent Title (German):Cells
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2020/01/29
Date of first Publication:2020/01/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/04/08
Tag:dendritic cells; macrophage; microlesions; perineurium; sciatic nerve; tumor pain
Volume:9
Issue:320
Note:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
HeBIS-PPN:46377261X
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung 4.0