BDNF介导的海马神经重塑在氯胺酮治疗抑郁-疼痛共病中的作用研究

The prevalence rate of the comorbidity of depression and chronic pain is really high, but the effective treatment is limited. Ketamine has demonstrated rapid and robust efficacy as an antidepressant by improving core depressive symptoms, also has analgesic effects, but there is unanswered question regarding whether it is effective in the comorbidity of depression and chronic pain. Our previous study found that ketamine can relieve depressive and pain symptoms in patients with the comorbidity of depression and chronic pain, with increasing serum BDNF level, and it was significantly positive correlation with efficacy to the increase of serum BDNF level. Several studies show a significant association between hippocampal synaptic plasticity damage and depression and chronic pain. Based on our previous study, we intend to enroll patients with the comorbidity of depression and chronic pain, and treat with ketamine. We are going to assess clinical symptom, detect serum BDNF levels and perform MRI in order to explore the association between efficacy, serum BDNF levels and the structure and function of the hippocampus. Than the comorbidity of depression and chronic pain animal models are established to verify the mechanisms of BDNF-mediated hippocampal neuroplasticity in ketamine in the treatment of comorbidity of depression and chronic pain. This study will provide new treatments for patients with the comorbidity of depression and chronic pain and help to understand its mechanism.

抑郁-疼痛共病发生率高，临床上缺少有效的治疗方法。氯胺酮既有快速抗抑郁作用，也可缓解疼痛，但不清楚对于两者共病的疗效如何。本课题组前期研究发现氯胺酮能有效减轻抑郁-疼痛共病患者的抑郁、疼痛症状，治疗后血清BDNF水平升高，BDNF上调水平与疗效相关。海马结构及功能的改变与抑郁症和慢性疼痛密切相关。因此我们推测：氯胺酮通过上调BDNF水平对抑郁-疼痛共病的海马神经重塑来发挥治疗作用。因此，本项目在前期研究基础上，以抑郁-疼痛共病患者为研究对象，给予氯胺酮治疗，通过治疗前后的临床症状评估、血液BDNF检测及海马磁共振检查，探讨疗效、BDNF、海马结构及功能的关系；在大鼠模型检测海马BDNF表达水平及观察海马神经元形态和数量的改变，验证BDNF介导的海马神经重塑在氯胺酮治疗抑郁-疼痛共病中的作用。本项目旨在证实氯胺酮治疗抑郁-疼痛共病的疗效，并明确其作用机制，为临床寻找治疗新靶点提供科学依据。

抑郁-疼痛共病发生率高，临床上缺少有效的治疗方法。氯胺酮既有快速抗抑郁作用，也可缓解疼痛，但不清楚对于两者共病的疗效如何。本课题组前期研究发现氯胺酮能有效减轻抑郁-疼痛共病患者的抑郁、疼痛症状，治疗后血清BDNF水平升高，BDNF上调水平与疗效相关。海马结构及功能的改变与抑郁症和慢性疼痛密切相关。因此我们推测：氯胺酮通过上调BDNF水平对抑郁-疼痛共病的海马神经重塑来发挥治疗作用。本项目在临床研究发现氯胺酮可快速有效改善抑郁、疼痛症状，氯胺酮治疗后抗抑郁有效率达60%，疼痛症状基本缓解，并且发现伴慢性疼痛的重性抑郁障碍患者抑郁症状改善更快、有效率更高。发现氯胺酮治疗后海马体积较治疗前增加，海马结构及功能调节在氯胺酮抗抑郁中起到重要作用；外周血BDNF水平增加，并且BDNF水平与氯胺酮抗抑郁作用密切相关。研究成果发表SCI论文4篇，中文核心期刊2篇，协助培养研究生毕业2名。本项目证实氯胺酮治疗抑郁-疼痛共病的疗效，为临床治疗提供新方法；并围绕BDNF-海马神经可塑性探索其作用机制，为临床寻找治疗新靶点提供科学依据。