Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain

作者：Chen, Peng^*; Wang, Chen; Gong, Qian; Chai, Yihui; Chen, Yunzhi; Song, Cuiwen; Wu, Yuanhua^*; Wang, Long^*

来源：iScience, 2023, 26(5): 106668.

DOI：10.1016/j.isci.2023.106668

• ARACHIDONIC-ACID
• ADENOSINE
• RAT
• PHARMACOLOGY
• DISORDERS
• INOSINE

Neuropathic pain (NeP) remains a significant clinical challenge owing to insuffi-cient awareness of its pathological mechanisms. We elucidated the aberrant metabolism of the cerebral cortex in NeP induced by the chronic constriction injury (CCI) using metabolomics and proteomics analyses. After CCI surgery, the values of MWT and TWL markedly reduced and maintained at a low level. CCI induced the significant dysregulation of 57 metabolites and 31 proteins in the cerebral cortex. Integrative analyses showed that the differentially ex-pressed metabolites and proteins were primarily involved in alanine, aspartate and glutamate metabolism, GABAergic synapse, and retrograde endocannabi-noid signaling. Targeted metabolomics and western blot analysis confirmed the alterations of some key metabolites and proteins in endogenous pain-modulatory system. In conclusion, our study revealed the alterations of endocannabinoids system and purinergic system in the CCI group, and provided a novel perspective on the roles of endogenous pain-modulatory system in the pathological mecha-nisms of NeP.

• 单位
  贵州大学; 广州中医药大学; 1; 南方医科大学