title: Adult Hippocampal Neurogenesis along the Dorsoventral Axis Contributes Differentially to Environmental Enrichment Combined with Voluntary Exercise in Alleviating Chronic Inflammatory Pain in Mice.
abstract: Cognitive behavioral therapy, such as environmental enrichment combined with voluntary exercise (EE-VEx), is under active investigation as an adjunct to pharmaceutical treatment for chronic pain. However, the effectiveness and underlying mechanisms of EE-VEx remain unclear. In mice with intraplantar injection of complete Freund's adjuvant, our results revealed that EE-VEx alleviated perceptual, affective, and cognitive dimensions of chronic inflammatory pain. These effects of EE-VEx on chronic pain were contingent on the occurrence of adult neurogenesis in the dentate gyrus in a functionally dissociated manner along the dorsoventral axis: neurogenesis in the ventral dentate gyrus participated in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas neurogenesis in the dorsal dentate gyrus was involved in EE-VEx's cognitive-enhancing effects. Chronic inflammatory pain was accompanied by decreased levels of brain-derived neurotrophic factor (BDNF) in the dentate gyrus, which were reversed by EE-VEx. Overexpression of BDNF in the dentate gyrus mimicked the effects of EE-VEx. Our results demonstrate distinct contribution of adult hippocampal neurogenesis along the dorsoventral axis to EE-VEx's beneficial effects on different dimensions of chronic pain.SIGNIFICANCE STATEMENTEnvironmental enrichment combined with voluntary exercise (EE-VEx) is under active investigation as an adjunct to pharmaceutical treatment for chronic pain, but its effectiveness and underlying mechanisms remain unclear. In a mouse model of inflammatory pain, the present study demonstrates that the beneficial effects of EE-VEx on chronic pain depend on adult neurogenesis with a dorsoventral dissociation along the hippocampal axis. Adult neurogenesis in the ventral dentate gyrus participates in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas that in the dorsal pole is involved in EE-VEx's cognitive-enhancing effects in chronic pain.
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Ling-Chi
authors.initials: LC
authors.lastname: Xu
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Long-Yu
authors.initials: LY
authors.lastname: Ma
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Shuang
authors.initials: S
authors.lastname: Cui
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liao
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and ywan@hsc.pku.edu.cn mingyi@bjmu.edu.cn.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing 100191, P.R. China.
authors.forename: You
authors.identifier: 0000-0001-6110-7192
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, and ywan@hsc.pku.edu.cn mingyi@bjmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Yi
mesh_terms: D000367:Age Factors; D000818:Animals; D059350:Chronic Pain / Q000473:pathology / Q000628:therapy*; D004777:Environment; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D007249:Inflammation / Q000473:pathology / Q000628:therapy; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology*
keywords: adult neurogenesis; anxiety; brain-derived neurotrophic factor; chronic inflammatory pain; environmental enrichment; hippocampus