Background
Neuropathic pain (NP) is a syndrome that arises from central or peripheral nerve injury, which manifests primarily as hyperalgesia, spontaneous pain, and allodynia. The recent trend has exhibited a shift towards the development of therapies for managing NP. Activation of autophagy is involved in the function of the glial cells, which may be implicated further to attenuate pain.
Conclusions
Our work showed that the analgesic impact of EA is partly related to AMPK/mTOR pathway activation and autophagy induction in microglial cells, providing a potential therapeutic target for NP.
Methods
In this study, the analgesic effects of electroacupuncture (EA) were evaluated among NP rats developed using spared nerve injury (SNI). Acupuncture treatment or EA was carried out after 7 days of SNI at two acupoints, i.e., the Zusanli (ST36) and Huantiao (GB30).
Results
The application of EA was found to attenuate mechanical hyperalgesia. The marker protein for microglial cells (CD11b) alone, without either the astrocyte marker or neuronal marker, was co-expressed with the autophagy indicator p62, as illustrated with immunofluorescence staining. Western blotting demonstrated that the expression levels of p62, Beclin-1, and LC3-II/LC3-I were elevated in the spinal cords of rats in the SNI group compared to the control levels. EA treatment resulted in reduced expression of p62, while the expressions of Beclin-1 and LC3-II/LC3-I were increased. The electron microscopy results indicated that EA could induce autophagy progression in the microglia of the spinal dorsal horn in SNI rats. Furthermore, we explored the causal relationship between EA-induced inhibition of NP and increased autophagic levels in microglia using the AMPK inhibitor compound C, and found that the mechanism of EA-induced analgesia may contribute to the promotion of AMPK/mTOR-mediated autophagy in spinal microglia. Conclusions: Our work showed that the analgesic impact of EA is partly related to AMPK/mTOR pathway activation and autophagy induction in microglial cells, providing a potential therapeutic target for NP.