A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevs.kogo Str, 17, 690041 Vladivostok, Russia.
Mar Drugs. 2020 Oct 15;18(10):516. doi: 10.3390/md18100516.
Chronic neuropathic pain is a condition that causes both sensory disturbances and a variety of functional disorders, indicating the involvement of various brain structures in pain pathogenesis. One of the factors underlying chronic neuropathic pain is neuroinflammation, which is accompanied by microglial activation and pro-inflammatory factor release. -docosahexaenoylethanolamine (DHEA, synaptamide) is an endocannabinoid-like metabolite synthesized endogenously from docosahexaenoic acid. Synaptamide exhibits anti-inflammatory activity and improves neurite outgrowth, neurogenesis, and synaptogenesis within the hippocampus. This study aims to evaluate the effects of synaptamide obtained by the chemical modification of DHA, extracted from the Far Eastern raw material on neuroinflammatory response and hippocampal neurogenesis changes during neuropathic pain. The study of microglial protein and cytokine concentrations was performed using immunohistochemistry and ELISA. The brain lipid analysis was performed using the liquid chromatography-mass spectrometry technique. Behavioral experiments showed that synaptamide prevented neuropathic pain-associated sensory and behavioral changes, such as thermal allodynia, impaired locomotor activity, working and long-term memory, and increased anxiety. Synaptamide attenuated microglial activation, release of proinflammatory cytokines, and decrease in hippocampal neurogenesis. Lipid analysis revealed changes in the brain -acylethanolamines composition and plasmalogen concentration after synaptamide administration. In conclusion, we show here that synaptamide may have potential for use in preventing or treating neuropathic cognitive pain and emotional effects.
慢性神经性疼痛是一种引起感觉障碍和多种功能障碍的病症，表明各种大脑结构参与了疼痛发病机制。慢性神经性疼痛的一个潜在因素是神经炎症，其伴随着小胶质细胞的激活和促炎因子的释放。-二十二碳六烯酰乙醇胺（DHEA，突触酰胺）是一种内源性合成的二十二碳六烯酸的内源性大麻素样代谢物。突触酰胺具有抗炎活性，可改善海马体内的神经突生长、神经发生和突触发生。本研究旨在评估从远东海藻中提取的经化学修饰的 DHA 得到的突触酰胺对神经炎症反应和神经性疼痛期间海马神经发生变化的影响。使用免疫组织化学和 ELISA 研究小胶质细胞蛋白和细胞因子浓度。使用液相色谱-质谱技术进行脑脂质分析。行为实验表明，突触酰胺可预防神经性疼痛相关的感觉和行为变化，如热痛觉过敏、运动活动受损、工作和长期记忆受损以及焦虑增加。突触酰胺可减弱小胶质细胞的激活、促炎细胞因子的释放和海马神经发生的减少。脂质分析显示，突触酰胺给药后大脑酰基乙醇胺组成和质体浓度发生变化。总之，我们在这里表明，突触酰胺可能具有预防或治疗神经性认知疼痛和情绪影响的潜力。
