Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats

Pain
Xing XiaoYou Wan

Abstract

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal inject...Continue Reading

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Citations

Feb 26, 2019·The British Journal of Dermatology·D RiccioL Arendt-Nielsen
Dec 20, 2017·Molecular Medicine Reports·Dongyan BaoYu Cao
Apr 6, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Ying-Jun LiuFang Fang
Nov 16, 2019·Journal of Cellular Physiology·Alexandra ManolacheStefan Eugen Szedlacsek
Jan 7, 2017·Biomedical Chromatography : BMC·Yang LiuWei Chen
Apr 21, 2021·Neuroscience Bulletin·Junli ZhaoRu-Rong Ji

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