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- W2897950921 abstract "Abstract Sensitization of the transient receptor potential ion channel vanilloid 1 (TRPV1) is critically involved in inflammatory pain. To date, manifold signaling cascades have been shown to converge onto TRPV1 and enhance its sensitization. However, many of them also play a role for nociceptive pain, which limits their utility as targets for therapeutic intervention. Here, we show that the vesicle transport through interaction with t-SNAREs homolog 1B (Vti1b) protein promotes TRPV1 sensitization upon inflammation in cell culture but leaves normal functioning of TRPV1 intact. Importantly, the effect of Vti1b can be recapitulated in vivo: Virus-mediated knockdown of Vti1b in sensory neurons attenuated thermal hypersensitivity during inflammatory pain without affecting mechanical hypersensitivity or capsaicin-induced nociceptive pain. Interestingly, TRPV1 and Vti1b are localized in close vicinity as indicated by proximity ligation assays and are likely to bind to each other, either directly or indirectly, as suggested by coimmunoprecipitations. Moreover, using a mass spectrometry–based quantitative interactomics approach, we show that Vti1b is less abundant in TRPV1 protein complexes during inflammatory conditions compared with controls. Alongside, we identify numerous novel and pain state-dependent binding partners of native TRPV1 in dorsal root ganglia. These data represent a unique resource on the dynamics of the TRPV1 interactome and facilitate mechanistic insights into TRPV1 regulation. We propose that inflammation-related differences in the TRPV1 interactome identified here could be exploited to specifically target inflammatory pain in the future." @default.
- W2897950921 created "2018-10-26" @default.
- W2897950921 creator A5026021153 @default.
- W2897950921 creator A5026284162 @default.
- W2897950921 creator A5028315501 @default.
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- W2897950921 creator A5064614134 @default.
- W2897950921 creator A5075309115 @default.
- W2897950921 creator A5084994331 @default.
- W2897950921 creator A5091493628 @default.
- W2897950921 date "2018-10-16" @default.
- W2897950921 modified "2023-10-14" @default.
- W2897950921 title "Vti1b promotes TRPV1 sensitization during inflammatory pain" @default.
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