Electroacupuncture Inhibits NLRP3-Mediated Microglial Pyroptosis to Ameliorate Chronic Neuropathic Pain in Rats

Journal of Pain Research, 2025 · DOI: https://doi.org/10.2147/JPR.S506569 · Published: March 7, 2025

Alternative Medicine Immunology Pain Management

Simple Explanation

Neuropathic pain (NP) is a persistent condition caused by nerve injury, affecting many worldwide. Current treatments have limitations, so there's a need for better therapies. This study explores how electroacupuncture (EA) might help alleviate NP, specifically by targeting pyroptosis, a type of cell death that contributes to inflammation. The study used a rat model of NP, and EA treatment was applied at specific acupoints. The researchers looked at pain sensitivity, inflammatory factors, and pyroptosis-related proteins. They found that EA reduced pain hypersensitivity and decreased levels of pro-inflammatory cytokines. This suggests that EA can alleviate chronic neuropathic pain by suppressing NLRP3 inflammasome activation in microglia, a type of immune cell in the brain. Pharmacological methods that specifically target against NLRP3 inflammasome were utilized to validate if EA alleviates NP via the NLRP3 inflammasome. The study showed that EA alleviates neuropathic pain by inhibiting NLRP3-mediated pyroptosis in microglia. This may serve as a viable treatment therapy for chronic NP.

Study Duration

Not specified

Participants

Male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
EA treatment significantly alleviated pain hypersensitivity by increasing the MWT and PWL in CCI rats.
2
EA reduced levels of pro-inflammatory cytokines IL-1β and TNF-α in the spinal tissue of CCI rats.
3
EA downregulated pyroptosis-related proteins (NLRP3, N-GSDMD, Cleaved Caspase-1, IL-18, IL-1β) in NP rats, indicating that EA attenuated the pyroptosis phenotype.

Research Summary

This study investigates the therapeutic effects of electroacupuncture (EA) on neuropathic pain (NP) in a rat model. The research focuses on the role of NLRP3 inflammasome-mediated pyroptosis in microglia and the potential of EA to inhibit this process. The key findings demonstrate that EA treatment significantly reduces pain hypersensitivity, suppresses spinal inflammatory responses, and mitigates CCI-induced pyroptosis levels in the spinal cord. EA was also found to inhibit microglia pyroptosis in the dorsal spinal cord of CCI rats. Pharmacological blocking of NLRP3 inflammasome activation alongside EA intervention further confirmed the role of NLRP3 inflammasome in the effects of EA on microglia pyroptosis and NP progression. The study concludes that EA may serve as a viable treatment therapy for chronic NP by suppressing NLRP3 inflammasome activation in microglia.

Practical Implications

Therapeutic Potential

EA at acupoints ST36 and GV20 emerges as a promising therapeutic modality for NP.

Mechanism Elucidation

The study sheds light on the molecular mechanisms underlying the effects of EA, particularly its role in inhibiting NLRP3 inflammasome activation.

Clinical Translation

The findings offer new avenues for treating NP and improving the quality of life for NP patients.

Study Limitations

1
Limited exploration of the mechanisms of non-classical pyroptosis pathways.
2
The study solely described the analgesic effect of EA mediated by regulating pyroptosis-specific indicators in NP rats, without considering other mechanisms.
3
Whether the combination of other acupoints can achieve the same effect and the mechanism of how EA treatment on ST36 and GV20 remotely inhibits pyroptosis activity remains unclear.

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