FSC231 can alleviate paclitaxel-induced neuralgia by inhibiting PICK1 and affecting related factors

Abstract

AIM\nTo explore the inhibitory effect of FSC231, a PDZ domain inhibitor of protein interacting with C kinase 1 (PICK1), on paclitaxel induced neuralgia and its possible pathways.\n\n\nMETHODS\nForty C57BL/6 mice were randomly divided into four groups (n\u2009=\u200910): the control group (CON), the FSC231 group (FSC), the paclitaxel group (PTL) and the FSC231 add paclitaxel group (F\u2009+\u2009P). Behavioral indictors of mice including the mechanical pain threshold, foot contraction reflex and inhibition rate were evaluated. ELISA, RT-qPCR and Western Blot were performed to determine the expression levels of IL-1β, IL-10, substance P and PICK1.\n\n\nRESULTS\nCompared with the control group, the foot contraction reflex time, mechanical pain threshold and IL-10 levels were significantly reduced in the PTL group, and IL-1β, substance P and PICK1 levels were significantly increased (P\u2009<\u20090.05). Compared with the PTL group, the foot contraction reflex time, mechanical pain threshold and IL-10 level were significantly increased, while IL-1β, SP and PICK1 levels were significantly decreased in the F\u2009+\u2009P group (P\u2009<\u20090.05).\n\n\nCONCLUSION\nFSC231 could alleviate paclitaxel-induced neuralgia by inhibiting PICK1 and affecting the secretion of inflammatory factors and substance P. The results of this study provide experimental basis for FSC231 to treat neuralgia caused by chemotherapy.