Apkarian A Vania, Mutso Amelia A, Centeno Maria V, Kan Lixin, Wu Melody, Levinstein Marjorie, Banisadr Ghazal, Gobeske Kevin T, Miller Richard J, Radulovic Jelena, Hen René, Kessler John A
Departments of Physiology and Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Department of Pharmacology, Columbia University, New York Psychiatric Institute, New York, NY, USA Departments of Molecular Pharmacology and Biological Chemistry and Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Pain. 2016 Feb;157(2):418-428. doi: 10.1097/j.pain.0000000000000332.
The full role of adult hippocampal neurogenesis (AHN) remains to be determined, yet it is implicated in learning and emotional functions, and is disrupted in negative mood disorders. Recent evidence indicates that AHN is decreased in persistent pain consistent with the idea that chronic pain is a major stressor, associated with negative moods and abnormal memories. Yet, the role of AHN in development of persistent pain has remained unexplored. In this study, we test the influence of AHN in postinjury inflammatory and neuropathic persistent pain-like behaviors by manipulating neurogenesis: pharmacologically through intracerebroventricular infusion of the antimitotic AraC; ablation of AHN by x-irradiation; and using transgenic mice with increased or decreased AHN. Downregulating neurogenesis reversibly diminished or blocked persistent pain; oppositely, upregulating neurogenesis led to prolonged persistent pain. Moreover, we could dissociate negative mood from persistent pain. These results suggest that AHN-mediated hippocampal learning mechanisms are involved in the emergence of persistent pain.
成体海马神经发生（AHN）的完整作用尚待确定，但它与学习和情绪功能有关，并且在负性情绪障碍中受到破坏。最近的证据表明，持续性疼痛中AHN减少，这与慢性疼痛是一种主要应激源的观点一致，慢性疼痛与负性情绪和异常记忆相关。然而，AHN在持续性疼痛发展中的作用尚未得到探索。在本研究中，我们通过操纵神经发生来测试AHN对损伤后炎症性和神经性持续性疼痛样行为的影响：通过脑室内注入抗有丝分裂剂阿糖胞苷进行药理学操纵；通过X射线照射消除AHN；以及使用AHN增加或减少的转基因小鼠。下调神经发生可逆地减轻或阻断持续性疼痛；相反，上调神经发生导致持续性疼痛延长。此外，我们可以将负性情绪与持续性疼痛区分开来。这些结果表明，AHN介导的海马学习机制参与了持续性疼痛的出现。
