Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Blocking NLRP3 inflammasome expression by RAS-like protein A mitigates neuropathic pain in chronic constriction injury rat models

Jin Qiu, Mian Xie

Department of Anesthesiology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China;

For correspondence:- Mian Xie Email: warert@sina.com Tel:+8615909397644

Accepted: 1 August 2021 Published: 31 August 2021

Citation: Qiu J, Xie M. Blocking NLRP3 inflammasome expression by RAS-like protein A mitigates neuropathic pain in chronic constriction injury rat models. Trop J Pharm Res 2021; 20(8):1615-1621 doi: 10.4314/tjpr.v20i8.10

© 2021 The authors.
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Abstract

Purpose: To investigate the role of RAS-like protein A (RalA) in lipopolysaccharide-induced inflammatory regulation in primary microglia of chronic constriction injury (CCI)-induced neuropathic pain in rat models.

Methods: In vitro, overexpression (OE) of RalA was performed in rat microglia using transfection procedure, and then LPS was used to provoke the inflammatory phenotype. In vivo, the rat model of neuropathic pain was induced using CCI and treated with LV-RalA. Neuroinflammatory levels including the expressions of IL-1β, IL-6, and TNF-α were detected. Moreover, the expressions of NF-κB p65, thioredoxin-interacting protein (TXNIP) and NLR family pyrin domain-containing 3?NLRP3?were examined in CCI rats and microglial cells. Finally, the functional evaluation was determined via mechanical allodynia and thermal hyperalgesia assays.

Results: The level of RalA decreased in the dorsal horn following CCI. OE of RalA in microglia after LPS insult and CCI-induced rat model significantly decreased the expressions of inflammation promoters (p < 0.05). Mechanistically, OE of RalA mitigated inflammatory response by inhibiting NF-κB/TXNIP/NLRP3 signaling pathway, thus attenuating neuropathic pain in microglial cells and CCI rats.

Conclusion: These results indicate that the OE of RalA plays a protective role in CCI-induced neuropathic pain via NF-κB/TXNIP/ NLRP3 axis. These findings may provide a promising therapeutic target for neuropathic pain.

Keywords: Neuropathic pain, NLRP3 inflammasome, NF-?B; RAS-like protein A, Microglia