在慢性痛与抑郁症患者中，疼痛和抑郁的共患比例高，提示慢性痛和抑郁可能有共通的神经病理机制。已有研究表明敲除 P2X7 受体基因可减轻疼痛反应，改善抑郁样行为。我们的前期结果也证实，系统给予P2X7 受体拮抗剂可改善慢性痛和抑郁共患模型小鼠的疼痛反应和抑郁样行为。其次，研究指出PI3K/AKT/mTOR 通路与两者均有关联，提示P2X7 受体介导的 PI3K/AKT/mTOR通路可能是慢性痛与抑郁症发病的关键调控因素。因此，本项目将整合行为学实验、电生理技术、分子和细胞生物学技术，从整体、细胞、分子和神经环路水平研究P2X7受体介导的 PI3K/AKT/mTOR信号通路在慢性痛与抑郁共患中的调控机制，为深入理解两者的发病和共患机制提供理论依据。

Pain and depression are two highly comorbid disorders in both chronic pain and depression patients, suggesting that they might share a common neurological mechanism. It has been reported that genetically knocking out P2X7 gene could relieve both painful responses and depressive syndromes in animal models. Out preliminary data also confirmed that systemically blocking P2X7 receptor by a selective antagonist increased both mechanical and thermal pain thresholds, and alleviated their depressive-like behavior. On the other hand, it has been reported that PI3K/AKT/mTOR signal pathway is involved in both chronic pain and depression, indicating that P2X7R-mediated PI3K/AKT/mTOR signaling pathway might play a key role in pain and depression. Therefore, using behavioral tests, electrophysiological techniques, molecular and cellular biological techniques, our project plans to study the effect of P2X7R-mediated PI3K/AKT/mTOR signaling pathway on comorbidity of chronic pain and depression, in order to provide evidence for understanding the mechanism of comorbidity of chronic pain and depression.