Yitian Yang1, Yuxiang Song2, Xuan Zhang3, Weixing Zhao2, Tao Ma4, Yi Liu2, Penglei Ma5, Yifan Zhao6, Hong Zhang7. 1. 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. yangyitiansdu@126.com. 2. 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. 3. Department of Anesthesiology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, 300060, China. 4. Department of Anesthesiology, Rocket Army Characteristic Medical Center, Beijing, 100088, China. 5. Department of Anesthesiology, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010030, China. 6. Department of Anesthesiology, The Fourth Medical Center of Chinese PLA General Hospital, Medical school of Chinese PLA, Beijing, 100037, China. 7. 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. mazuimao301@163.com.
Abstract
RATIONALE: 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. OBJECTIVES: The present study evaluated the effects of ketamine in rats with the comorbidity of CPSP and depression. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RATIONALE: Clinically, chronic postsurgical pain (CPSP) is very common. Many CPSPpatients 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. OBJECTIVES: The present study evaluated the effects of ketamine in rats with the comorbidity of CPSP and depression. METHODS: 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. RESULTS: 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 CPSPrats. Additionally, ketamine reduced proinflammatory cytokines, inhibited oxidative stress, and elevated BDNF levels in rat hippocampus. CONCLUSIONS: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.
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