Role of spinal RIP3 in inflammatory pain and electroacupuncture-mediated analgesic effect in mice.
Role of spinal RIP3 in inflammatory pain and electroacupuncture-mediated analgesic effect in mice.
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DOI：
10.1016/j.lfs.2022.120839
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发表时间：
2022-07
期刊：
影响因子：
6.1
通讯作者：
Yidan Zhang;Yuanzeng Wang;Wen-Jun Zhao;Luyao Li;Lei Li;Yanyan Sun;Jin-Ping Shao;Xiuhua Ren;Weidong Zang;Jing Cao
中科院分区：
文献类型：
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作者：
Yidan Zhang;Yuanzeng Wang;Wen-Jun Zhao;Luyao Li;Lei Li;Yanyan Sun;Jin-Ping Shao;Xiuhua Ren;Weidong Zang;Jing Cao
目的电针（EA）是治疗炎症性疼痛的一种潜在有效方法。受体相互作用蛋白 3 (RIP3) 触发 NOD 样受体家族 Pyrin 结构域 3 (NLRP3) 炎性体；据报道，激活独立于坏死性凋亡。然而，RIP3在炎性疼痛中的作用及其电针诱导的镇痛作用尚不清楚。主要方法建立完全弗氏佐剂（CFA）疼痛模型后，对小鼠进行电针（2 Hz，2 mA）治疗。分别通过鞘内注射GSK-843（一种特异性RIP3抑制剂）或显微注射慢病毒-RIP3来抑制或激活脊髓RIP3。使用机械镇痛法和热镇痛法来评估小鼠的缩爪阈值和缩爪潜伏期。采用定量聚合酶链反应（qRT-PCR）和蛋白质印迹法评估小鼠脊髓背角（SDH）中RIP3和NLPR3的表达。主要发现注射CFA后脊髓RIP3和NLPR3的表达显着增加。鞘内注射 GSK-843 和 EA 均可减轻 CFA 诱导的机械疼痛和热痛行为，并抑制 CFA 小鼠 SDH 中 RIP3 和 NLRP3 的表达。 RIP3的过表达会引起小鼠的疼痛样症状，并抑制电针对炎性痛的调节作用。意义：我们的研究结果表明，电针的镇痛作用可能与抑制SDH中RIP3和NLRP3的表达有关。这项研究可以为了解 EA 镇痛作用的潜在脊柱机制提供潜在的见解。
AimsElectroacupuncture (EA) is a potentially useful treatment for inflammatory pain. Receptor-interacting protein 3 (RIP3) triggers the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome; activation independent of necroptosis has been reported. However, the role of RIP3 in inflammatory pain and its EA-induced analgesic effects remains unclear.Main methodsMice were treated with EA (2 Hz, 2 mA) after complete Freund's adjuvant (CFA) pain models were established. Inhibition or activation of spinal RIP3 was achieved by intrathecal administration of GSK-843 (a specific RIP3 inhibitor) or microinjection of lentivirus-RIP3, respectively. Mechanical analgesiometry and thermal analgesiometry were used to assess paw withdrawal threshold and paw withdrawal latency in mice. Quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to evaluate the expression of RIP3 and NLPR3 in spinal dorsal horn (SDH) of mice.Key findingsThe expression of spinal RIP3 and NLPR3 increased significantly after CFA injection. Both intrathecal administration of GSK-843 and EA alleviated mechanical and thermal pain behaviors induced by CFA and inhibited the expression of RIP3 and NLRP3 in the SDH of CFA mice. Over-expression of RIP3 induces pain-like symptoms in mice and inhibits the regulatory effects of EA on inflammatory pain.SignificanceOur results indicate that the EA analgesia effect may be related to suppression of RIP3 and NLRP3 expression in the SDH. This study could provide potential insights into the underlying spinal mechanisms involved in the analgesic effect of EA.