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The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury

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
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Item Type: Article
Type of entry: Secondary publication
Title: The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury
Language: English
Date: 19 December 2022
Place of Publication: Darmstadt
Year of primary publication: 2022
Publisher: MDPI
Journal or Publication Title: International Journal of Molecular Sciences
Volume of the journal: 23
Issue Number: 22
Collation: 19 Seiten
DOI: 10.26083/tuprints-00022974
Corresponding Links:
Origin: Secondary publication DeepGreen
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.

Uncontrolled Keywords: neuropathic pain, lipid mediators, ceramides, sensory neurons, nerve injury, FKBP51
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-229748
Additional Information:

This article belongs to the Special Issue Lipid Signaling and Metabolism in Inflammation-Associated Diseases

Classification DDC: 500 Science and mathematics > 570 Life sciences, biology
600 Technology, medicine, applied sciences > 610 Medicine and health
Divisions: 07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
Date Deposited: 19 Dec 2022 12:38
Last Modified: 14 Nov 2023 19:05
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/22974
PPN: 503240664
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