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Published on: October 6, 2022
FSC231 can alleviate paclitaxel-induced neuralgia by inhibiting PICK1 and affecting related factors
Guangjie Wang1, Xi Zhang1, Xuelian Pan1
1Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Aim:
To 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.
Methods:
Forty C57BL/6 mice were randomly divided into four groups (n = 10): the control group (CON), the FSC231 group (FSC), the paclitaxel group (PTL) and the FSC231 add paclitaxel group (F + P). 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.
Results:
Compared 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 < 0.05). 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 + P group (P < 0.05).
Conclusion:
FSC231 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.
Insights
FSC231, a PICK1 inhibitor, alleviates paclitaxel-induced neuralgia in mice. This study shows FSC231 reduces pain and inflammation by targeting protein interacting with C kinase 1 (PICK1), offering a potential chemotherapy side-effect treatment.
Area of Science:
- Neuroscience and Pharmacology
- Molecular Biology
- Pain Research
Background:
- Paclitaxel is a widely used chemotherapy agent.
- Paclitaxel can induce neuropathic pain, a debilitating side effect.
- Protein interacting with C kinase 1 (PICK1) plays a role in neuronal signaling.
Purpose of the Study:
- To investigate the efficacy of FSC231, a PICK1 inhibitor, in mitigating paclitaxel-induced neuralgia.
- To elucidate the underlying molecular pathways involved in FSC231's inhibitory effect.
Main Methods:
- Utilized a mouse model of paclitaxel-induced neuralgia.
- Assessed behavioral pain responses including mechanical pain threshold and foot contraction reflex.
- Quantified levels of inflammatory markers (IL-1β, IL-10) and neuropeptides (Substance P) using ELISA, RT-qPCR, and Western Blot.
Main Results:
- Paclitaxel treatment significantly increased pain behaviors and elevated levels of IL-1β, Substance P, and PICK1.
- FSC231 treatment reversed these effects, significantly reducing pain behaviors and decreasing IL-1β, Substance P, and PICK1 levels.
- FSC231 treatment also increased levels of the anti-inflammatory cytokine IL-10.
Conclusions:
- FSC231 demonstrates significant potential in alleviating paclitaxel-induced neuralgia.
- The mechanism involves the inhibition of PICK1 and modulation of inflammatory factors and Substance P.
- These findings support FSC231 as a therapeutic candidate for chemotherapy-induced neuralgia.
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