Chronic pain causes a persistent anxiety state leading to increased ethanol intake in CD1 mice
Chronic pain causes a persistent anxiety state leading to increased ethanol intake in CD1 mice
复制标题
DOI：
10.1177/0269881115622238
复制
发表时间：
2016-02-01
影响因子：
4.1
通讯作者：
Valverde, Olga
中科院分区：
文献类型：
--
作者：
Gonzalez-Sepulveda, Marta;Pozo, Oscar J.;Valverde, Olga
情绪障碍和慢性疼痛密切相关，但在了解慢性和神经性疼痛在抑郁症发病机制中的作用方面取得的进展有限。为了探索介导疼痛和抑郁样行为之间关联的病理机制，我们研究了神经性疼痛对CD 1小鼠焦虑样和绝望行为发展的时间依赖性影响。我们分析了行为数据，神经炎症反应和小鼠前额叶皮层神经递质（谷氨酸和5-羟色胺）水平的变化。坐骨神经部分结扎后5天和20天，坐骨神经手术小鼠分别表现出持久的焦虑样和绝望行为。神经病理性疼痛小鼠前额叶皮层谷氨酸能神经传递和IL-1细胞因子表达增强。我们没有发现血清素代谢，细胞因子IL-6或脑源性神经营养因子水平的变化。虽然坐骨神经手术的小鼠暴露于间歇性乙醇摄入量（20%v/v），使用在黑暗中饮用的程序消耗的乙醇量高于假手术小鼠，热异常性疼痛和绝望的行为没有减弱乙醇消耗。我们的研究结果揭示了多巴胺能神经传递和疼痛诱导的情绪障碍之间的关联，并表明适度的乙醇消费并不能缓解小鼠慢性疼痛相关的伤害性和抑郁行为。
Mood disorders and chronic pain are closely linked, but limited progress has been made in understanding the role of chronic and neuropathic pain in the aetiopathogenesis of depression. To explore the pathological mechanisms that mediate the association between pain and depressive-like behaviours, we studied the time-dependent effect of neuropathic pain on the development of anxiety-like and despair behaviours in CD1 mice. We analysed behavioural data, neuroinflammation reactions and changes in neurotransmitter (glutamate and serotonin) levels in the mouse prefrontal cortex. Sciatic-operated mice displayed long-lasting anxiety-like and despair behaviours, starting 5 and 20 days after partial sciatic nerve ligation, respectively. Glutamatergic neurotransmission and IL-1 cytokine expression were enhanced in the prefrontal cortex of mice with neuropathic pain. We found no change in serotonin metabolism, cytokine IL-6 or brain-derived neurotrophic factor levels. While sciatic-operated mice exposed to intermittent ethanol intake (20% v/v) using the drinking in the dark procedure consumed higher amounts of ethanol than sham-operated mice, thermal allodynia and despair behaviour were not attenuated by ethanol consumption. Our findings reveal an association between glutamatergic neurotransmission and pain-induced mood disorders, and indicate that moderate ethanol consumption does not relieve nociceptive and depressive behaviours associated with chronic pain in mice.