Study on the involvement of TRPA1 and TRPV4 in cholestatic pruritus model
Proceedings for Annual Meeting of The Japanese Pharmacological Society(2022)
Abstract
Cholestasis is one of the chronic diseases that leads to itching with unknown underlying mechanism. TRP channels have attracted attention as nociceptor of the primary sensory nerves related to acute itching behavior. On the other hand, the involvement of TRP channels in systemic itch-like behavior in chronic cholestatic pruritus model has not been much studied., we used a cholestatic model to elucidate the involvement of TRPA1 and TRPV4 in cholestatic pruritus. Male C57BL/6 strain Mice for wild type, TRPA1 knockout mice (A1KO) and TRPV4 knockout mice (V4KO) were used for experimental animal. Two of the bile ducts connecting the right and caudate lobes of liver were ligated with silk thread and the bile ducts between the two ligation sites were cut (BDL). The number of spontaneous scratching bouts with hindlimb is observed as an index of itch behavior. The scratching bouts significantly was augmented in 5th week after the surgery in BDL, compared to sham group. BDL significantly increased the level of mRNA in TRPA1 and TRPV4 in dorsal root ganglion, although that of TRPV4 in the skin of cervical region in BDL group was significantly decreased in comparison to sham. The BDL-induced scratching bouts were significantly decreased in A1KO, compared to in WT. The results suggest that TRPA1 were involved in scratching behavior in cholestatic pruritus model.
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Key words
cholestatic pruritus model,trpv4,trpa1
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