Anesthesia and Operation Center, The First Medical Center of Chinese PLA General Hospital, Medical school of Chinese PLA, No. 28 Fuxing Road, Beijing, 100853, China.
Department of Anesthesiology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, 300060, China.
Psychopharmacology (Berl). 2020 Jun;237(6):1657-1669. doi: 10.1007/s00213-020-05490-3. Epub 2020 Mar 3.
Clinically, chronic postsurgical pain (CPSP) is very common. Many CPSP patients may experience depression. Thus far, little is known about the mechanism of the comorbidity of CPSP and depression. Ketamine has been confirmed to possess analgesic and rapid antidepressant effects, but it is unclear whether ketamine can relieve the comorbidity of CPSP and depression.
The present study evaluated the effects of ketamine in rats with the comorbidity of CPSP and depression.
We induced CPSP in rats by thoracotomy and screened for rats with or without depression-like phenotype by hierarchical cluster analysis based on the results of depression-related behavioral experiments. Subsequently, rats were intraperitoneally injected with ketamine (20 mg/kg) and were evaluated by mechanical withdrawal threshold, cold hyperalgesia test, sucrose preference test, forced swimming test, and open field test. The inflammatory-related cytokines (IL-1, IL-6, TNF-α, nuclear factor-kappaB), oxidative stress parameters (superoxide dismutase, malondialdehyde, glutathione, catalase), and brain-derived neurotrophic factor (BDNF) in rat hippocampus were detected.
In the hippocampus of rats with the comorbidity of CPSP and depression, IL-1, IL-6, TNF-α, nuclear factor-kappaB, and malondialdehyde were significantly increased, while superoxide dismutase, glutathione, catalase, and BDNF were significantly decreased. Ketamine relieved depression but did not attenuate hyperalgesia in CPSP rats. Additionally, ketamine reduced proinflammatory cytokines, inhibited oxidative stress, and elevated BDNF levels in rat hippocampus.
Ketamine can rapidly relieve CPSP-induced depression in rats, which may be related to the reduction of proinflammatory cytokines, regulating oxidative stress and increasing BDNF in the hippocampus.
临床上，慢性术后疼痛（CPSP）非常常见。许多 CPSP 患者可能会出现抑郁。迄今为止，对于 CPSP 和抑郁共病的发病机制知之甚少。氯胺酮已被证实具有镇痛和快速抗抑郁作用，但尚不清楚氯胺酮是否能缓解 CPSP 和抑郁共病。
本研究评估氯胺酮对 CPSP 合并抑郁大鼠的作用。
我们通过开胸手术诱导大鼠 CPSP，并基于抑郁相关行为实验的结果进行层次聚类分析，筛选出具有或不具有抑郁表型的大鼠。随后，大鼠腹腔注射氯胺酮（20mg/kg），并通过机械撤回避痛阈值、冷超敏试验、蔗糖偏好试验、强迫游泳试验和旷场试验进行评估。检测大鼠海马炎性相关细胞因子（IL-1、IL-6、TNF-α、核因子-kappaB）、氧化应激参数（超氧化物歧化酶、丙二醛、谷胱甘肽、过氧化氢酶）和脑源性神经营养因子（BDNF）。
在 CPSP 合并抑郁大鼠的海马体中，IL-1、IL-6、TNF-α、核因子-kappaB 和丙二醛明显升高，而超氧化物歧化酶、谷胱甘肽、过氧化氢酶和 BDNF 明显降低。氯胺酮缓解了抑郁，但并未减轻 CPSP 大鼠的痛觉过敏。此外，氯胺酮降低了促炎细胞因子，抑制了氧化应激，提高了大鼠海马体中的 BDNF 水平。
氯胺酮可快速缓解 CPSP 大鼠的抑郁，这可能与减少海马体中的促炎细胞因子、调节氧化应激和增加 BDNF 有关。
