TY  - JOUR
A1  - Cohnen, Jennifer
A1  - Kornstädt, Lisa
A1  - Hahnefeld, Lisa Katharina
A1  - Ferreirós Bouzas, Nerea
A1  - Pierre, Sandra
A1  - Köhl, Ulrike
A1  - Deller, Thomas
A1  - Geisslinger, Gerd
A1  - Scholich, Klaus
T1  - Tumors provoke inflammation and perineural microlesions at adjacent peripheral nerves
T2  - Cells
N2  - 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.
KW  - dendritic cells
KW  - macrophage
KW  - microlesions
KW  - perineurium
KW  - sciatic nerve
KW  - tumor pain
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54428
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-544287
N1  - 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.
VL  - 9
IS  - 320
PB  - MDPI
CY  - Basel
ER  -