Neuropharmacology Laboratory of Physiology Department, Basic Medical College of Nanchang University, Nanchang 330006, People's Republic of China.
Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, People's Republic of China.
ACS Chem Neurosci. 2020 Dec 16;11(24):4387-4397. doi: 10.1021/acschemneuro.0c00623. Epub 2020 Dec 7.
The hippocampus is an important region for the interaction between depression and pain. Studies show that the P2X4 receptor plays key role in neuropathic pain. This work investigated the potential implication of the P2X4 receptor in the hippocampus in comorbidity of chronic pain and depression. The rat model induced by chronic constriction injury (CCI) plus unpredictable chronic mild stress (UCMS) was used in this study. Our data showed that CCI plus UCMS treatment resulted in abnormal changes in pain and depressive-like behaviors in the rat, accompanied by the upregulated expression of P2X4, NLRP3 (NOD-like receptor protein 3) inflammasome, and interleukin-1β and the activation of p38 MAPK in the hippocampus. The P2X4 antagonist 5-BDBD reversed these abnormal changes in the hippocampus, relieved hippocampal neuronal damage, and alleviated the abnormal pain and depressive-like behaviors in the CCI plus UCMS treated rats. These findings suggest that the P2X4 receptor in the hippocampus may mediate and significantly contribute to the pathological processes of comorbid pain and depression.
海马体是抑郁和疼痛相互作用的重要区域。研究表明，P2X4 受体在神经病理性疼痛中起关键作用。本研究旨在探讨 P2X4 受体在慢性疼痛和抑郁共病的海马体中的潜在意义。本研究采用慢性缩窄性损伤（CCI）加不可预测慢性轻度应激（UCMS）诱导的大鼠模型。我们的数据显示，CCI 加 UCMS 处理导致大鼠出现疼痛和抑郁样行为的异常变化，同时伴随着海马体中 P2X4、NLRP3（NOD 样受体蛋白 3）炎性小体、白细胞介素-1β表达上调和 p38 MAPK 激活。P2X4 拮抗剂 5-BDBD 逆转了海马体中的这些异常变化，减轻了海马体神经元损伤，并缓解了 CCI 加 UCMS 处理大鼠的异常疼痛和抑郁样行为。这些发现表明，海马体中的 P2X4 受体可能介导并显著促进共病性疼痛和抑郁的病理过程。
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