Refine
Has Fulltext
- yes (4)
Is part of the Bibliography
- yes (4)
Year of publication
- 2022 (4) (remove)
Document Type
- Journal article (4)
Language
- English (4) (remove)
Keywords
- 3D ex vivo models (1)
- CNS disorders (1)
- CRPS (1)
- IL-6 (1)
- MMP9 (1)
- RECK (1)
- TTFields (1)
- Tumor Treating Fields (TTFields) (1)
- blood nerve barrier (1)
- blood–brain barrier (1)
- cerebEND (1)
- claudin-1 (1)
- dexamethasone (1)
- glioblastoma (1)
- glucocorticoid receptor (1)
- ischemia (1)
- isosteviol sodium (STVNA) (1)
- microRNA (1)
- neuropathic pain (1)
- organoids (1)
- organotypic hippocampal slice cultures (OHSC) (1)
- tumor slice cultures (1)
Institute
- Neurochirurgische Klinik und Poliklinik (4)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (3)
- Institut für Anatomie und Zellbiologie (1)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (1)
- Neurologische Klinik und Poliklinik (1)
- Pathologisches Institut (1)
EU-Project number / Contract (GA) number
- 602133 (1)
Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin-1 in both injured and spared nerves. Moreover, the putative miR-21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR-21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR-21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR-21 after nerve injury reversed it. In summary, the data support a novel role for miR-21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9.