Ming Li-Guo, Hu Dong-Xia, Zuo Cheng, Zhang Wen-Jun
Department of Gastrointestinal surgery, the Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China.
Department of Rehabilitation Medicine, the Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province 343000, China.
Biomed Pharmacother. 2023 Jun;162:114713. doi: 10.1016/j.biopha.2023.114713. Epub 2023 Apr 20.
The pathological mechanism of neuropathic pain is complex, which seriously affects the physical and mental health of patients, and its treatment is also difficult. The role of G protein-coupled P2Y12 receptor in pain has been widely recognized and affirmed. After nerve injury, stimulated cells can release large amounts of nucleotides into the extracellular matrix, act on P2Y12 receptor. Activated P2Y12 receptor activates intracellular signal transduction and is involved in the development of pain. P2Y12 receptor activation can sensitize primary sensory neurons and receive sensory information. By transmitting the integrated information through the dorsal root of the spinal cord to the secondary neurons of the posterior horn of the spinal cord. The integrated information is then transmitted to the higher center through the ascending conduction tract to produce pain. Moreover, activation of P2Y12 receptor can mediate immune cells to release pro-inflammatory factors, increase damage to nerve cells, and aggravate pain. While inhibits the activation of P2Y12 receptor can effectively relieve pain. Therefore, in this article, we described P2Y12 receptor antagonists and their pharmacological properties. In addition, we explored the potential link between P2Y12 receptor and the nervous system, discussed the intrinsic link of P2Y12 receptor and neuropathic pain and as a potential pharmacological target for pain suppression.
神经性疼痛的病理机制复杂,严重影响患者身心健康,其治疗也较为困难。G蛋白偶联P2Y12受体在疼痛中的作用已得到广泛认可和肯定。神经损伤后,受刺激的细胞可将大量核苷酸释放到细胞外基质中,作用于P2Y12受体。激活的P2Y12受体激活细胞内信号转导并参与疼痛的发展。P2Y12受体激活可使初级感觉神经元敏感化并接收感觉信息。通过脊髓背根将整合后的信息传递至脊髓后角的次级神经元。然后,整合后的信息通过上行传导束传递至高级中枢以产生疼痛。此外,P2Y12受体激活可介导免疫细胞释放促炎因子,增加对神经细胞的损伤并加重疼痛。而抑制P2Y12受体的激活可有效缓解疼痛。因此,在本文中,我们描述了P2Y12受体拮抗剂及其药理特性。此外,我们探讨了P2Y12受体与神经系统之间的潜在联系,讨论了P2Y12受体与神经性疼痛的内在联系以及作为疼痛抑制的潜在药理学靶点。