2. Academic Validation
  3. Gallic Acid Improves Comorbid Chronic Pain and Depression Behaviors by Inhibiting P2X7 Receptor-Mediated Ferroptosis in the Spinal Cord of Rats

Gallic Acid Improves Comorbid Chronic Pain and Depression Behaviors by Inhibiting P2X7 Receptor-Mediated Ferroptosis in the Spinal Cord of Rats

  • ACS Chem Neurosci. 2023 Jan 31. doi: 10.1021/acschemneuro.2c00532.
Runan Yang 1 2,  Liran Shi 1 3 2,  Han Si 4,  Zihui Hu 1 2,  Lifang Zou 5 6,  Lin Li 1 2,  Xiumei Xu 1 2,  Günther Schmalzing 7,  Hong Nie 8,  Guilin Li 1 2,  Shuangmei Liu 1 2,  Shangdong Liang 1 2,  Changshui Xu 1 2
Affiliations

Affiliations

  • 1 Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang, Jiangxi 330006, P. R. China.
  • 2 Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, P. R. China.
  • 3 The People's Hospital of Jiawang of Xuzhou, Xuzhou, Jiangsu 221011, P. R. China.
  • 4 Nursing College, Medical College of Nanchang University, Nanchang, Jiangxi 330006, P. R. China.
  • 5 Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P. R. China.
  • 6 Clinical Research Center for Hematologic Disease of Jiangxi Province, Nanchang, Jiangxi 330006, P. R. China.
  • 7 Institute of Clinical Pharmacology, RWTH Aachen University, Aachen 52062, Germany.
  • 8 Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P. R. China.
PMID: 36719132 DOI: 10.1021/acschemneuro.2c00532
Abstract

Ferroptosis is an inflammatory programmed cell death process that is dependent on iron deposition and lipid peroxidation. The P2X7 receptor not only is involved in the pain process but also is closely related to the onset of depression. Gallic acid (3,4,5-trihydroxybenzoic acid), which is naturally found in a variety of Plants, exhibits anti-inflammatory, antioxidant, and analgesic effects. This study established a rat model with the comorbidity of chronic constrictive injury (CCI) plus chronic unpredictable mild stress (CUMS) to explore the role and mechanism of gallic acid in the treatment of pain and depression comorbidity. Our experimental results showed that pain and depression-like behaviors were more obvious in the chronic constriction injury (CCI) plus chronic unpredictable mild stimulation (CUMS) group than they were in the sham operation group, and the P2X7-reactive oxygen species (ROS) signaling pathway was activated. The tissue iron concentration was increased, and mitochondrial damage was observed in the CCI plus CUMS group. These results were alleviated with gallic acid treatment. Therefore, we speculate that gallic acid inhibits the Ferroptosis of the spinal microglia by regulating the P2X7-ROS signaling pathway and relieves the behavioral changes in rats with comorbid pain and depression.

Keywords

P2X7 receptor; comorbidity of pain and depression; ferroptosis; gallic acid; microglia.

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