Lee Hwayoung, Im Jiyun, Won Hansol, Nam Wooyoung, Kim Young Ock, Lee Sang Won, Lee Sanghyun, Cho Ik-Hyun, Kim Hyung-Ki, Kwon Jun-Tack, Kim Hak-Jae
Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea.
Development of Ginseng and Medical Plants Research Institute, Rural Administration, Eumseong 27709, Korea.
Korean J Physiol Pharmacol. 2017 Jul;21(4):361-370. doi: 10.4196/kjpp.2017.21.4.361. Epub 2017 Jun 26.
Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.
先前的报告表明，身体和心理压力可能引发纤维肌痛（FM）。压力是抑郁症和记忆障碍发展的重要风险因素。抗抑郁药已被用于预防压力诱导的异常疼痛感觉。在各种抗抑郁药中，据报道噻奈普汀能够预防慢性应激导致的神经退行性变，并逆转海马体积的减小。为了评估噻奈普汀对FM症状的可能影响，我们构建了一种由束缚应激和间歇性冷应激诱导的FM动物模型。所有小鼠均使用电子von Frey麻醉计和哈格里夫斯设备进行伤害性感受测定。为了评估噻奈普汀与脑源性神经营养因子（BDNF）、环磷酸腺苷反应元件结合蛋白（CREB）和磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）表达水平之间的关系，进行了蛋白质印迹和免疫组织化学分析。在行为分析中，伤害性感受测试表明，与对照组相比，FM组的疼痛阈值显著降低。内侧前额叶皮质（mPFC）和海马的蛋白质印迹和免疫组织化学分析表明，与对照组相比，FM组中BDNF和p-CREB蛋白表达下调。然而，噻奈普汀在行为测试和蛋白质水平上恢复了这些变化。因此，这种FM动物模型可能有助于研究BDNF-CREB通路与疼痛之间的联系机制。我们的结果表明，噻奈普汀可能对FM具有潜在的治疗效果。
