Electroacupuncture alleviates neuropathic pain caused by spared nerve injury by promoting AMPK/mTOR-mediated autophagy in dorsal root ganglion macrophage

Qian Xu; Cong Niu; Jiajing Li; Cheng Hu; Menglin He; Xizi Qiu; Qiang Yao; Weiqian Tian; Minhao Zhang

doi:10.21037/atm-22-5920

Electroacupuncture alleviates neuropathic pain caused by spared nerve injury by promoting AMPK/mTOR-mediated autophagy in dorsal root ganglion macrophage

Ann Transl Med. 2022 Dec;10(24):1341. doi: 10.21037/atm-22-5920.

Authors

Qian Xu^#¹, Cong Niu^#², Jiajing Li^#¹, Cheng Hu^#³, Menglin He⁴, Xizi Qiu⁴, Qiang Yao⁴, Weiqian Tian¹, Minhao Zhang^{5

6}

Affiliations

¹ Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
² Department of Anesthesiology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, The Second Hospital of Chinese Medicine in Jiangsu Province, Nanjing, China.
³ Department of Pain Management, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China.
⁴ The First Clinical Medical School, Nanjing University of Chinese Medicine, Nanjing, China.
⁵ Department of Anesthesiology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
⁶ Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.

^# Contributed equally.

Abstract

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.

Keywords: Neuropathic pain (NP); autophagy; dorsal root ganglia (DRG); electroacupuncture (EA).