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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00770

Dihydromyricetin alleviates diabetic neuropathic pain and depression comorbidity symptoms by inhibiting P2X7 receptor

Shu Guan1, Yulin Shen1, 2, Huixiang Ge1, Wei Xiong3, Lingkun He3, Lijuan Liu3, Cancan Yin3, Xingyu Wei1 and  Yun Gao1, 4*
  • 1Department of Physiology, Basic Medical College, Nanchang University, China
  • 2Sport Biological Centre, China Institute of Sport Science, China
  • 3Affiliated Stomatological Hospital of Nanchang University, China
  • 4Jiangxi Provincial Key Laboratory of autonomic nervous function and disease, China

Diabetic neuropathic pain (DNP) and depression (MDD) are common complications of diabetes and mutually affect each other. As a member of the ATP-gated ion channel family, P2X7 receptor is associated with the transduction of pain signal and the onset of depression. The aim of this study was to investigate the effects of dihydromyricetin (DHM) on rats with comorbid DNP and MDD. After the comorbid model was established, rat behavior changes were monitored by measuring the mechanical withdrawal threshold, thermal withdrawal latency, sugar water preference, immobility time in the forced-swim test, and open-field test parameters. The expression of P2X7 receptor in the dorsal root ganglia (DRGs), spinal cord, and hippocampus were assessed by quantitative real-time PCR, Western blotting, and double immunofluorescence. We found that hyperalgesia, allodynia, and depressive behaviors of rats with comorbid DNP and MDD were relieved by treatment with DHM or application of a short-hairpin RNA (shRNA) for P2X7 receptor. The expression levels of P2X7, phospho-extracellular signal–regulated kinase 1/2, tumor necrosis factor-α, and interleukin-1β were increased in the DRGs, spinal cord, and hippocampus of rats in the Model group but restored after DHM or P2X7 shRNA treatment. In conclusion, P2X7 receptor in the DRGs, spinal cord, and hippocampus participates in the transduction of DNP and MDD signals. DHM seems to relieve comorbid DNP and MDD by reducing the expression of P2X7 receptor in the DRGs, spinal cord, and hippocampus and may be an effective new drug for the treatment of patients with both DNP and MDD.

Keywords: P2X7 receptor, Diabetic neuropathic pain, Dorsal root ganglion, Spinal Cord, Hippocampus, Dihydromyricetin, Major depressive disorder

Received: 13 Sep 2018; Accepted: 24 Sep 2019.

Copyright: © 2019 Guan, Shen, Ge, Xiong, He, Liu, Yin, Wei and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yun Gao, Nanchang University, Department of Physiology, Basic Medical College, Nanchang, China, gaoyun@ncu.edu.cn