Anxiety- and Depression-Like Behavior and Impaired Neurogenesis Evoked by Peripheral Neuropathy Persist following Resolution of Prolonged Tactile Hypersensitivity
Anxiety- and Depression-Like Behavior and Impaired Neurogenesis Evoked by Peripheral Neuropathy Persist following Resolution of Prolonged Tactile Hypersensitivity
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DOI：
10.1523/jneurosci.0312-14.2014
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发表时间：
2014-09-10
影响因子：
5.3
通讯作者：
Usdin, Ted B.
中科院分区：
文献类型：
--
作者：
Dimitrov, Eugene L.;Tsuda, Mumeko C.;Usdin, Ted B.
疼痛和抑郁经常与最初的损伤相关，并且往往在最初的损伤消失后持续存在。对于基础神经科学和精神病学来说，确定抑郁症在多大程度上仍然与慢性疼痛期间持续的身体不适存在因果关系，或者成为独立的，是基础神经科学和精神病学的重要问题。很难区分持续的厌恶感觉输入的影响及其长期后果，这是一个重大的障碍，特别是在动物模型中。为了解决局部身体不适与其更具全局性的后果之间的关系，我们研究了逆转神经病理性疼痛的小鼠模型期间和之后的细胞和行为变化。通过在坐骨神经周围放置塑料套筒而产生的触觉过敏在套筒被移除后几天内就消失了。相反，神经袖放置后的高架O迷宫、强迫游泳、Y迷宫自发交替和新物识别测试成绩的变化，在摘除神经袖后至少3周，或在机械灵敏度完全正常化后10~15d保持不变。用双皮质素和增殖细胞核抗原的表达来衡量海马神经发生，在神经袖带放置后也受到抑制，在摘除袖带后3周仍然受到抑制。FosB在杏仁核中央核和脊髓背角的表达仅在持续痛觉异常的小鼠中升高。相比之下，FosB在痛觉消失和持续行为影响的小鼠的杏仁基底外侧核中保持升高。这些观察表明，不同的过程控制着触觉过敏和与神经病理性痛觉异常相关的行为变化和神经发生障碍。
Pain and depression are frequently associated with and often persist after resolution of an initial injury. Identifying the extent to which depression remains causally associated with ongoing physical discomfort during chronic pain, or becomes independent of it, is an important problem for basic neuroscience and psychiatry. Difficulty in distinguishing between effects of ongoing aversive sensory input and its long-term consequences is a significant roadblock, especially in animal models. To address this relationship between localized physical discomfort and its more global consequences, we investigated cellular and behavioral changes during and after reversing a mouse model of neuropathic pain. Tactile allodynia produced by placing a plastic cuff around the sciatic nerve resolved within several days when the cuff was removed. In contrast, the changes in elevated O-maze, forced-swim, Y-maze spontaneous alternation and novel-object recognition test performance that developed after nerve cuff placement remained for at least 3 weeks after the nerve cuffs were removed, or 10-15 d following complete normalization of mechanical sensitivity. Hippocampal neurogenesis, measured by doublecortin and proliferating cell nuclear antigen expression, was also suppressed after nerve cuff placement and remained suppressed 3 weeks after cuff removal. FosB expression was elevated in the central nucleus of the amygdala and spinal cord dorsal horn only in mice with ongoing allodynia. In contrast, FosB remained elevated in the basolateral amygdala of mice with resolved nociception and persisting behavioral effects. These observations suggest that different processes control tactile hypersensitivity and the behavioral changes and impaired neurogenesis that are associated with neuropathic allodynia.