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.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.
Background: Dorsal root ganglia (DRG) plays an important role in mediating the peripheral sensation transduction through the primary afferent neurons in pain research. Neuropathic pain (NP) is a syndrome of hyperalgesia, spontaneous pain and allodynia caused by central or peripheral nerve injury. Recent trends of study are turning towards the development of therapies for the management of NP. Activation of autophagy in glial cells in the spinal cord has been reported to be associated with attenuation of NP, but the autophagic process in DRG is rarely studied. Methods:The analgesic effect of electroacupuncture (EA) was evaluated in NP-induced rats developed using spared nerve injury (SNI). Acupuncture or EA was performed after 7 days of SNI at Zusanli (ST36) and Huantiao (GB30) acupoints. Then, the activation status of autophagy process in DRGs of rats treated with SNI and EA were investigated, and the possible mechanism of the analgesic effect of EA were explored.Results: Application of EA has been found to reduce mechanical hyperalgesia. Autophagy indicator p62 was colocalized with the marker proteins for macrophages (CD11b), but not with NeuN (marker protein for neurons) or GFAP (marker protein for satellite glial cells), as shown by immunofluorescence. Western blots results indicate that the expression levels of p62, Beclin-1 and LC3-II in the L4-L6 DRG of rats in the SNI group were increased, compared with that in the control group. EA treatment resulted in decreased expression of p62 and increased expression of Beclin-1 and LC3-II/LC3-I. Furthermore, we explored the causal relationship between EA-induced suppression of NP and increased levels of autophagy in DRG using electron microscopy and the AMPK (AMP-activated protein kinase) inhibitor compound C.Conclusions: SNI achieved a significant upregulation of autophagy levels in DRG macrophages.Furthermore, EA attenuated NP, which may contribute to the promotion of AMPK/mTOR (mammalian target of rapamycin)-mediated autophagy in DRG macrophages. Therefore, this strategy provides a new target for therapeutic intervention of NP.
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