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Adult hippocampal neurogenesis along the dorsoventral axis contributes differentially to environmental enrichment combined with voluntary exercise in alleviating chronic inflammatory pain in mice.

Adult hippocampal neurogenesis along the dorsoventral axis contributes differentially to environmental enrichment combined with voluntary exercise in alleviating chronic inflammatory pain in mice.
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Zheng J, Jiang YY, Xu LC, Ma LY, Liu FY, Cui S, Cai J, Liao FF, Wan Y, Yi M,


Zheng J, Jiang YY, Xu LC, Ma LY, Liu FY, Cui S, Cai J, Liao FF, Wan Y, Yi M, (click to view)

Zheng J, Jiang YY, Xu LC, Ma LY, Liu FY, Cui S, Cai J, Liao FF, Wan Y, Yi M,

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The Journal of neuroscience : the official journal of the Society for Neuroscience 2017 03 14() pii 3333-16
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 intra-plantar injection of complete Freund’s adjuvant (CFA), 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. Over-expression of BDNF in the dentate 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.

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