SNi公司
神经损伤
神经病理性疼痛
周围神经损伤
医学
痛觉超敏
慢性应激
神经营养因子
慢性疼痛
神经生长因子
内科学
内分泌学
痛觉过敏
神经科学
心理学
麻醉
伤害
受体
化学
生物化学
坐骨神经
水解
酸水解
作者
Greg J. Norman,Kate Karelina,N Zhang,James C. Walton,John Morris,A. Courtney DeVries
摘要
The physiological link between neuropathic pain and depression remains unknown despite a high comorbidity between these two disorders. A mouse model of spared nerve injury (SNI) was used to test the hypothesis that nerve injury precipitates depression through the induction of inflammation in the brain, and that prior exposure to stress exacerbates the behavioral and neuroinflammatory consequences of nerve injury. As compared with sham surgery, SNI induced mechanical allodynia, and significantly increased depressive-like behavior. Moreover, SNI animals displayed increased interleukin-1β (IL-1β) gene expression within the frontal cortex and concurrent increases in the expression of glial fibrillary acidic protein (GFAP) within the periaqueductal grey (PAG). Additionally, exposure to chronic restraint stress for 2 weeks before SNI exacerbated mechanical allodynia and depressive-like behavior, and resulted in an increase in IL-1β gene expression in the frontal cortex and brain-derived neurotrophic factor (BDNF) gene expression in PAG. Treatment with metyrapone (MET), a corticosteroid synthesis inhibitor, before stress eliminated deleterious effects of chronic stress on SNI. Finally, this study showed that interference with IL-1β signaling, through administration of IL-1 receptor antagonist (IL-1ra), ameliorated the effects of neuropathic pain on depressive-like behavior. Taken together, these data suggest that peripheral nerve injury leads to increased cytokine expression in the brain, which in turn, contributes to the development of depressive-like behavior. Furthermore, stress can facilitate the development of depressive-like behavior after nerve injury by promoting IL-1β expression.
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