Effects of analgesic or antidepressant drugs on pain- or stress-evoked hippocampal and spinal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression in the rat
Effects of analgesic or antidepressant drugs on pain- or stress-evoked hippocampal and spinal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression in the rat
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DOI：
10.1124/jpet.106.109470
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发表时间：
2006-12-01
影响因子：
3.5
通讯作者：
McCarson, Kenneth E.
中科院分区：
文献类型：
--
作者：
Duric, Vanja;McCarson, Kenneth E.
临床研究表明，患有慢性疼痛的人通常也会受到抑郁症的困扰。抗抑郁药用于治疗某些类型的慢性疼痛;然而，对其作用机制知之甚少。本研究探讨了非甾体抗炎药和三环类抗抑郁药对大鼠脊髓背角和海马疼痛和应激诱发基因表达的影响。用吲哚美辛或丙咪嗪对大鼠进行预处理，然后用足底完全弗氏佐剂或制动应激进行攻击。结果表明，吲哚美辛显着减少伤害性相关的外周水肿，痛觉过敏，并逆转疼痛引起的上调神经激肽（NK）-1受体和脑源性神经营养因子（BDNF）的基因表达在脊髓中的水平没有统计学差异。然而，吲哚美辛并没有防止海马中这些基因的显著疼痛诱导的下调约50%，这表明尽管镇痛药物治疗减少了脊髓中的伤害性感觉激活，但不足以防止疼痛对海马的影响。相反，虽然丙咪嗪没有提供显着的行为镇痛，它显着阻断疼痛和应激引起的海马和脊髓NK-1和BDNF基因表达的变化。因此，这些结果表明，单独应用镇痛药或抗抑郁药不能完全防止持续性疼痛对中枢神经系统内“感觉”和“情感”处理的行为和分子效应。
Clinical studies show that people suffering from chronic pain are often also burdened by depression. Antidepressants are used to treat some types of chronic pain; however, little is known about their mechanisms of action. This study addressed the effects of a nonsteroidal anti-inflammatory drug and a tricyclic antidepressant drug on pain- and stress-evoked gene expression in the rat spinal cord dorsal horn and hippocampus. Rats were pretreated with either indomethacin or imipramine and then challenged with either intraplantar complete Freund's adjuvant or a bout of immobilization stress. Results showed that indomethacin significantly reduced nociception-related peripheral edema, hyperalgesia, and reversed the pain-evoked up-regulation of neurokinin (NK)-1 receptor and brain-derived neurotrophic factor (BDNF) gene expression in the spinal cord to levels not statistically different from controls. However, indomethacin did not protect against significant pain-induced down-regulation of these genes in the hippocampus by approximately 50%, suggesting that although analgesic drug treatment reduces nociceptive sensory activation in the spinal cord, it is insufficient to prevent the impact of pain on the hippocampus. Conversely, although imipramine did not provide significant behavioral analgesia, it significantly blocked both pain-and stress-evoked alterations in hippocampal and spinal NK-1 and BDNF gene expression. Thus, these results show that application of either analgesic or antidepressant drugs alone does not fully protect against both the behavioral and molecular effects of persistent pain on both " sensory" and " affective" processing within the central nervous system.