Zhang, Y, Miao, Q, Shi, S et al. (13 more authors) (2022) Protein disulfide isomerase modulation of TRPV1 controls heat hyperalgesia in chronic pain. Cell Reports, 39 (1). ISSN 2211-1247
Abstract
Protein disulfide isomerase (PDI) plays a key role in maintaining cellular homeostasis by mediating protein folding via catalyzing disulfide bond formation, breakage, and rearrangement in the endoplasmic reticulum. Increasing evidence suggests that PDI can be a potential treatment target for several diseases. However, the function of PDI in the peripheral sensory nervous system is unclear. Here we report the expression and secretion of PDI from primary sensory neurons is upregulated in inflammatory and neuropathic pain models. Deletion of PDI in nociceptive DRG neurons results in a reduction in inflammatory and neuropathic heat hyperalgesia. We demonstrate that secreted PDI activates TRPV1 channels through oxidative modification of extracellular cysteines of the channel, indicating that PDI acts as an unconventional positive modulator of TRPV1. These findings suggest that PDI in primary sensory neurons plays an important role in development of heat hyperalgesia and can be a potential therapeutic target for chronic pain.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Author(s). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0) (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | PDI; TRPV1; cysteine oxidation; DRG; chronic pain |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Apr 2022 13:37 |
Last Modified: | 13 Apr 2022 13:37 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.celrep.2022.110625 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:185653 |