Wedel, Saskia ; Hahnefeld, Lisa ; Alnouri, Mohamad Wessam ; Offermanns, Stefan ; Hausch, Felix ; Geisslinger, Gerd ; Sisignano, Marco (2022)
The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury.
In: International Journal of Molecular Sciences, 2022, 23 (22)
doi: 10.26083/tuprints-00022974
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Neuropathic pain is a pathological pain state with a broad symptom scope that affects patients after nerve injuries, but it can also arise after infections or exposure to toxic substances. Current treatment possibilities are still limited because of the low efficacy and severe adverse effects of available therapeutics, highlighting an emerging need for novel analgesics and for a detailed understanding of the pathophysiological alterations in the onset and maintenance of neuropathic pain. Here, we show that the novel and highly specific FKBP51 inhibitor SAFit2 restores lipid signaling and metabolism in nervous tissue after nerve injury. More specifically, we identify that SAFit2 restores the levels of the C16 dihydroceramide, which significantly reduces the sensitization of the pain-mediating TRPV1 channel and subsequently the secretion of the pro-inflammatory neuropeptide CGRP in primary sensory neurons. Furthermore, we show that the C16 dihydroceramide is capable of reducing acute thermal hypersensitivity in a capsaicin mouse model. In conclusion, we report for the first time the C16 dihydroceramide as a novel and crucial lipid mediator in the context of neuropathic pain as it has analgesic properties, contributing to the pain-relieving properties of SAFit2.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Wedel, Saskia ; Hahnefeld, Lisa ; Alnouri, Mohamad Wessam ; Offermanns, Stefan ; Hausch, Felix ; Geisslinger, Gerd ; Sisignano, Marco |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2022 |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | International Journal of Molecular Sciences |
| Jahrgang/Volume einer Zeitschrift: | 23 |
| (Heft-)Nummer: | 22 |
| Kollation: | 19 Seiten |
| DOI: | 10.26083/tuprints-00022974 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/22974 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Neuropathic pain is a pathological pain state with a broad symptom scope that affects patients after nerve injuries, but it can also arise after infections or exposure to toxic substances. Current treatment possibilities are still limited because of the low efficacy and severe adverse effects of available therapeutics, highlighting an emerging need for novel analgesics and for a detailed understanding of the pathophysiological alterations in the onset and maintenance of neuropathic pain. Here, we show that the novel and highly specific FKBP51 inhibitor SAFit2 restores lipid signaling and metabolism in nervous tissue after nerve injury. More specifically, we identify that SAFit2 restores the levels of the C16 dihydroceramide, which significantly reduces the sensitization of the pain-mediating TRPV1 channel and subsequently the secretion of the pro-inflammatory neuropeptide CGRP in primary sensory neurons. Furthermore, we show that the C16 dihydroceramide is capable of reducing acute thermal hypersensitivity in a capsaicin mouse model. In conclusion, we report for the first time the C16 dihydroceramide as a novel and crucial lipid mediator in the context of neuropathic pain as it has analgesic properties, contributing to the pain-relieving properties of SAFit2. |
| Freie Schlagworte: | neuropathic pain, lipid mediators, ceramides, sensory neurons, nerve injury, FKBP51 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-229748 |
| Zusätzliche Informationen: | This article belongs to the Special Issue Lipid Signaling and Metabolism in Inflammation-Associated Diseases |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 19 Dez 2022 12:38 |
| Letzte Änderung: | 02 Aug 2024 12:46 |
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| Suche nach Titel in: | TUfind oder in Google |
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- The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury. (deposited 19 Dez 2022 12:38) [Gegenwärtig angezeigt]
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