Department of Anesthesiology, Shanxi Bethune Hospital, No.99 Longcheng Street, Taiyuan, Shanxi Province, 030012, People's Republic of China.
Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People's Republic of China.
Metab Brain Dis. 2020 Oct;35(7):1085-1093. doi: 10.1007/s11011-020-00599-y. Epub 2020 Jul 8.
Depression is one of main symptoms accompanying thermal hyperalgesia and mechanical allodynia induced by inflammatory pain. On physiological level, depressive symptoms could be attenuated by sufficient level of hippocampal neural plasticity. Adult hippocampal neurogenesis (AHN) plays critical roles in clearing panic memory, increasing psychiatric adaptability and preventing depressive emotion. Thus, targeting AHN is the applicable strategy to improve neural functions impaired and attenuate inflammatory pain. Previous reports indicate natural compound baicalin (BA) is one of the effective agents to promote AHN. In present study, we tested the effects of BA in mouse model of inflammatory pain as well as its biological underpinning. Behavioral tests indicate that BA treatment attenuated thermal hyperalgesia, mechanical allodynia and depressive symptoms. Meanwhile, treatment of BA promoted growth and differentiation of neural stem cells in hippocampus. AHN blocker temozolomide (TMZ) resulted in significant suppressed effects of BA to promote AHN, suggesting the critical role of AHN in regulating behavioral effects of BA to inflammatory pain. Akt plays the critical roles in the effects of BA to attenuate inflammatory pain induced symptoms. Prohibiting of Akt with GSK960693 dramatically prevented the effects of BA in attenuating inflammatory pain induced behavioral symptoms. Taken together, BA is the potential pain killer to alleviating inflammatory pain via Akt-mediated adult hippocampal neurogenesis.
抑郁症是炎症性疼痛引起的热痛觉过敏和机械性痛觉过敏的主要伴随症状之一。在生理水平上，足够水平的海马神经可塑性可以减轻抑郁症状。成年海马神经发生（AHN）在清除恐慌记忆、增加精神适应性和预防抑郁情绪方面起着关键作用。因此，针对 AHN 是改善受损神经功能和减轻炎症性疼痛的适用策略。先前的报告表明，天然化合物黄芩素（BA）是促进 AHN 的有效药物之一。在本研究中，我们测试了 BA 在炎症性疼痛小鼠模型中的作用及其生物学基础。行为测试表明，BA 治疗可减轻热痛觉过敏、机械性痛觉过敏和抑郁症状。同时，BA 处理促进了海马中神经干细胞的生长和分化。AHN 阻断剂替莫唑胺（TMZ）显著抑制了 BA 促进 AHN 的作用，表明 AHN 在调节 BA 对炎症性疼痛的行为作用中起关键作用。Akt 在 BA 减轻炎症性疼痛相关症状的作用中起着关键作用。用 GSK960693 抑制 Akt 可显著阻止 BA 减轻炎症性疼痛诱导的行为症状。综上所述，BA 通过 Akt 介导的成年海马神经发生，是一种有潜力的缓解炎症性疼痛的止痛药。
