Usefulness of antidepressants for improving the neuropathic pain-like state and pain-induced anxiety through actions at different brain sites
Usefulness of antidepressants for improving the neuropathic pain-like state and pain-induced anxiety through actions at different brain sites
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DOI：
10.1038/sj.npp.1301590
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发表时间：
2008-07-01
影响因子：
7.6
通讯作者：
Suzuki, Tsutomu
中科院分区：
文献类型：
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作者：
Matsuzawa-Yanagida, Kiyomi;Narita, Minoru;Suzuki, Tsutomu
临床上，众所周知，慢性疼痛会导致抑郁、焦虑和生活质量下降。关于疼痛和情绪之间的关系已经有很多报道。我们之前报道了慢性疼痛诱导焦虑与中枢神经系统阿片能功能的变化。在这项研究中，我们评估了几种类型的抗抑郁药在慢性神经性疼痛样状态下的抗焦虑样作用，并寻找抗抑郁药表现出抗焦虑或抗感觉作用的大脑部位。坐骨神经结扎后第7 ~ 28天小鼠表现出热痛觉过敏和触觉异常性痛。结扎后4周，这些小鼠在光暗测试和升高的+迷宫测试中表现出显著的焦虑相关行为。在这些条件下，反复服用抗抑郁药，包括三环抗抑郁药（TCA）丙咪嗪、血清素去甲肾上腺素再摄取抑制剂（SNRI） milnacpran和选择性血清素再摄取抑制剂（SSRI）帕罗西汀，可显著预防慢性神经性疼痛引起的焦虑相关行为。这些抗抑郁药还能显著减少热痛觉过敏和触觉异常性疼痛。此外，向杏仁核基底外侧或扣带皮层微注射帕罗西汀可减少焦虑相关行为，向初级体感皮层微注射帕罗西汀可显著减轻热痛觉过敏。这些发现表明，5 -羟色胺类抗抑郁药对治疗与慢性神经性疼痛相关的焦虑有效，也可能对治疗伴有情绪障碍（如焦虑）的神经性疼痛有用。此外，SSRIs通过作用于不同的大脑区域显示出抗焦虑和抗感觉作用。
Clinically, it is well known that chronic pain induces depression, anxiety, and a reduced quality of life. There have been many reports on the relationship between pain and emotion. We previously reported that chronic pain induced anxiety with changes in opioidergic function in the central nervous system. In this study, we evaluated the anxiolytic-like effects of several types of antidepressants under a chronic neuropathic pain-like state and searched for the brain site of action where antidepressants show anxiolytic or antinociceptive effects. Sciatic nerve-ligated mice exhibited thermal hyperalgesia and tactile allodynia from days 7 to 28 after nerve ligation. At 4 weeks after ligation, these mice showed a significant anxiety-related behavior in the light-dark test and the elevated plus-maze test. Under these conditions, repeated administration of antidepressants, including the tricyclic antidepressant (TCA) imipramine, the serotonin noradrenaline reuptake inhibitor (SNRI) milnacipran, and the selective serotonin reuptake inhibitor (SSRI) paroxetine, significantly prevented the anxiety-related behaviors induced by chronic neuropathic pain. These antidepressants also produced a significant reduction in thermal hyperalgesia and tactile allodynia. Moreover, the microinjection of paroxetine into the basolateral amygdala or cingulate cortex reduced anxiety-related behavior, and microinjection into the primary somatosensory cortex significantly attenuated thermal hyperalgesia. These findings suggest that serotonergic antidepressants are effective for treating anxiety associated with chronic neuropathic pain and may be useful for treating neuropathic pain with emotional dysfunction such as anxiety. Furthermore, SSRIs show anxiolytic and antinociceptive effects by acting on different brain regions.