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- W3121427018 abstract "Abstract Sigma-1 receptors (Sig-1Rs) are endoplasmic reticulum (ER) chaperones implicated in neuropathic pain. Here we examine if the Sig-1R may relate to neuropathic pain at the level of dorsal root ganglia (DRG). We focus on the neuronal excitability of DRG in a “spare nerve injury” (SNI) model of neuropathic pain in rats and find that Sig-1Rs likely contribute to the genesis of DRG neuronal excitability by decreasing the protein level of voltage-gated Cav2.2 as a translational inhibitor of mRNA. Specifically, during SNI, Sig-1Rs translocate from ER to the nuclear envelope via a trafficking protein Sec61β. At the nucleus, the Sig-1R interacts with cFos and binds to the promoter of 4E-BP1, leading to an upregulation of 4E-BP1 that binds and prevents eIF4E from initiating the mRNA translation for Cav2.2. Interestingly, in Sig-1R knockout HEK cells, Cav2.2 is upregulated. In accordance with those findings, we find that intra-DRG injection of Sig-1R agonist (+)pentazocine increases frequency of action potentials via regulation of voltage-gated Ca2+ channels. Conversely, intra-DRG injection of Sig-1R antagonist BD1047 attenuates neuropathic pain. Hence, we discover that the Sig-1R chaperone causes neuropathic pain indirectly as a translational inhibitor." @default.
- W3121427018 created "2021-02-01" @default.
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- W3121427018 date "2021-01-18" @default.
- W3121427018 modified "2023-10-17" @default.
- W3121427018 title "Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain" @default.
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- W3121427018 doi "https://doi.org/10.1007/s12035-020-02276-8" @default.
- W3121427018 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8128747" @default.
- W3121427018 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33459966" @default.
- W3121427018 hasPublicationYear "2021" @default.
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