Disrupting USP5/Cav3.2 interactions protects female mice from mechanical hypersensitivity during peripheral inflammation

Abstract Cav3.2Â T-type calcium channels are important for the signaling of nociceptive information in the primary afferent pain pathway. During neuropathy and peripheral inflammation, Cav3.2 channels are upregulated due to an increased association with the deubiquitinase USP5. Disrupting these interactions in male mice by the use of cell permeant peptides reverses mechanical and thermal hypersensitivity. Here we explore the effects of interfering with USP5 binding to the channel in female mice with synchronized estrous cycle. We show that intrathecal delivery of a cell-penetrating TAT peptide corresponding to the UBPc domain of USP5 fully reverses mechanical hypersensitivity in mice intraplantarly injected with Complete Freundâ s Adjuvant. Hence, the USP5 mediated dysregulation of Cav3.2 channel activity does not exhibit sex differences, and potential therapeutics targeting this interaction should be effective in both male and female subjects.

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PID https://www.doi.org/10.6084/m9.figshare.c.4273337.v1
PID https://www.doi.org/10.6084/m9.figshare.c.4273337
URL http://dx.doi.org/10.6084/m9.figshare.c.4273337.v1
URL http://dx.doi.org/10.6084/m9.figshare.c.4273337
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Author Gadotti, Vinicius
Author Zamponi, Gerald
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Collected From Datacite
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Publication Date 2018-01-01
Publisher Figshare
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keyword FOS: Physical sciences
keyword FOS: Biological sciences
keyword FOS: Clinical medicine
system:type other
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Source https://science-innovation-policy.openaire.eu/search/other?orpId=dedup_wf_001::00a54c7cf82c8b51374ac8748f62d0dc
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Last Updated 19 December 2020, 14:07 (CET)
Created 19 December 2020, 14:07 (CET)