Electroacupuncture as a promising therapeutic strategy for chronic constriction injury-induced neuropathic pain: Insights into the PPARα/SIRT1/NF-κB axis.

BACKGROUND

Electroacupuncture (EA), a therapeutic modality that combines traditional acupuncture with electrical stimulation, is a promising non-pharmacological therapy for alleviating neuropathic pain (NP). However, the molecular mechanisms through which EA exerts its effects in the context of NP remain inadequately understood.

METHODS

In this study, a rat model of chronic constriction injury (CCI) was employed to investigate the therapeutic effects of EA on NP and the underlying molecular mechanisms. Pain-related behaviors were assessed via mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and footprint. RNA sequencing (RNA-Seq) was used to identify key targets. Immuno-fluorescence, Western blot, enzyme-linked immunosorbent assay (ELISA), and RT-qPCR were performed to evaluate the expression of related molecules and pro-inflammatory factors. Neuronal excitability was recorded by whole-cell patch-clamp.

RESULTS

We demonstrated that EA stimulation increased the expression of PPARα in spinal dorsal horn (SDH) neurons, which subsequently enhanced silent information regulator transcript 1(SIRT1) levels and reduced the acetylated NF-κB (Ac-NF-κB) /total NF-κB ratio. This cascade suppressed microglial activation and decreased the levels of pro-inflammatory factors (IL-1β, TNF-α, IL-6), thereby reducing neuronal hyperexcitability (sEPSCs, rheobase, and AP firing) and ultimately alleviating pain-related behaviors (including MWT, TWL, and sen-sorimotor function).

CONCLUSIONS

Our findings suggest that EA stimulation alleviates NP by regulating the PPARα/SIRT1/NF-κB axis in CCI rats. This study not only provides innovative insights into the mechanisms underlying EA's analgesic effects but also highlights this axis as a promising therapeutic target for NP management.