Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Brain Res. 2021 May 1;1758:147329. doi: 10.1016/j.brainres.2021.147329. Epub 2021 Feb 1.
Chronic-pain patients often suffer from depression. In rodent models of neuropathic pain, animals develop depression-like and anxiety behaviors, indicating a relationship between chronic pain and affective disorders. However, the underlying neurobiological mechanisms linking chronic pain and depression are not yet fully understood. Neurogenesis in the hippocampus is a fundamental process related to brain plasticity. Reduced neurogenesis has been associated with the development of mood disorders and cognitive impairments. The current study aims to elucidate the underlying long-term changes in brain plasticity induced by neuropathic pain in mice at a time point when depression-like behavior has already developed. Furthermore, our focus is set on alterations in neurogenesis in the hippocampus. We found that manifestation of anxiety- and depressive-like behavior as well as cognitive impairment co-occur with decreased survival of newly generated cells but not with impaired proliferative activity or reduced number of immature neurons in the dentate gyrus area of the hippocampus. Moreover, we detected an impairment of differentiation of newly generated cells into mature calbindin-positive neurons, accompanied with a shift towards increased differentiation into astroglial cells. These findings indicate that a reduction in mature functional neurons, rather than reduced proliferation or neuronal progenitor cells, are the long-term changes in hippocampal plasticity that manifest in neuropathic pain conditions after depression-like behavior has developed.
慢性疼痛患者常伴有抑郁。在神经病理性疼痛的啮齿动物模型中，动物会出现类似抑郁和焦虑的行为，表明慢性疼痛与情感障碍之间存在关联。然而，将慢性疼痛与抑郁联系起来的潜在神经生物学机制尚不完全清楚。海马体中的神经发生是与大脑可塑性相关的基本过程。神经发生减少与情绪障碍和认知障碍的发展有关。本研究旨在阐明神经病理性疼痛在已经出现类似抑郁行为的时间点诱导的大脑可塑性的长期变化。此外，我们的重点是海马体中神经发生的变化。我们发现，焦虑和抑郁样行为以及认知障碍的表现与新生成细胞的存活减少有关，但与增殖活性受损或海马齿状回区未成熟神经元数量减少无关。此外，我们检测到新生成的细胞向成熟的钙结合蛋白阳性神经元分化受损，同时向星形胶质细胞分化增加。这些发现表明，成熟功能性神经元的减少，而不是增殖或神经元祖细胞的减少，是在出现类似抑郁行为后，神经病理性疼痛状态下海马体可塑性的长期变化。
