Schwann cell autocrine and paracrine regulatory mechanisms, mediated by Allopregnanolone and BDNF, Modulate PKC[epsilon] in peripheral sensory neurons
Protein kinase type C-ε (PKCε) plays important roles in the sensitization of primary afferent nociceptors, such as ion channel phosphorylation, that in turn promotes mechanical hyperalgesia and pain chronification. In these neurons, PKCε is modulated through the local release of mediators by the sur...
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| Autori principali: | , , , , , , , , , , |
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| Natura: | Article (Journal) |
| Lingua: | inglese |
| Pubblicazione: |
11 August 2020
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| In: |
Cells
Year: 2020, Volume: 9, Fascicolo: 8, Pages: 1-17 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9081874 |
| Accesso online: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cells9081874 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2073-4409/9/8/1874 
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| Note sull'autore: | Veronica Bonalume, Lucia Caffino, Luca F. Castelnovo, Alessandro Faroni, Flavio Giavarini, Sheng Liu, Donatella Caruso, Martin Schmelz, Fabio Fumagalli, Richard W. Carr and Valerio Magnaghi |
| Riassunto: | Protein kinase type C-ε (PKCε) plays important roles in the sensitization of primary afferent nociceptors, such as ion channel phosphorylation, that in turn promotes mechanical hyperalgesia and pain chronification. In these neurons, PKCε is modulated through the local release of mediators by the surrounding Schwann cells (SCs). The progesterone metabolite allopregnanolone (ALLO) is endogenously synthesized by SCs, whereas it has proven to be a crucial mediator of neuron-glia interaction in peripheral nerve fibers. Biomolecular and pharmacological studies on rat primary SCs and dorsal root ganglia (DRG) neuronal cultures were aimed at investigating the hypothesis that ALLO modulates neuronal PKCε, playing a role in peripheral nociception. We found that SCs tonically release ALLO, which, in turn, autocrinally upregulated the synthesis of the growth factor brain-derived neurotrophic factor (BDNF). Subsequently, glial BDNF paracrinally activates PKCε via trkB in DRG sensory neurons. Herein, we report a novel mechanism of SCs-neuron cross-talk in the peripheral nervous system, highlighting a key role of ALLO and BDNF in nociceptor sensitization. These findings emphasize promising targets for inhibiting the development and chronification of neuropathic pain. |
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| Descrizione del documento: | Im Titel ist Epsilon als griechischer Buchstabe dargestellt Gesehen am 27.07.2026 |
| Descrizione fisica: | Online Resource |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9081874 |