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辣椒素刺激后表达 C-fos 的脊髓甘氨酸能和 GABA 能神经元在伴有对侧神经病理性疼痛的大鼠中增加。

Spinal glycinergic and GABAergic neurons expressing C-fos after capsaicin stimulation are increased in rats with contralateral neuropathic pain.

机构信息

Department of Neuroscience, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

出版信息

Neuroscience. 2011 Nov 24;196:265-75. doi: 10.1016/j.neuroscience.2011.08.050. Epub 2011 Aug 27.

DOI:10.1016/j.neuroscience.2011.08.050
PMID:21889971
Abstract

There is increasing evidence that pain transmission on one side of the body is influenced by a painful state on the other side. We have investigated this phenomenon by studying the activation pattern (using C-fos labeling) of spinal glycinergic and GABAergic (Gly/GABA) neurons after capsaicin injection in the ipsilateral hind paw of rats that were preconditioned with an acute or chronic pain stimulus in the contralateral hind paw or rats that were not preconditioned (control). For this purpose, fluorescent in situ hybridization with GlyT2 and GAD67 mRNA probes was combined with fluorescent C-fos immunohistochemistry. Rats were preconditioned with acute (capsaicin, Complete Freund's Adjuvant (CFA) 1.5 h), chronic inflammatory (CFA 20 h and 4 days), neuropathic (spared nerve injury (SNI) 2 weeks), or control pain stimuli (saline 20 h and 4 days; sham-SNI 2 weeks). We found that after capsaicin injection in rats preconditioned with CFA inflammation (4 days), sham-SNI or with SNI neuropathic pain, the numbers (27 ± 3, 21 ± 2, and 21 ± 2, respectively) and percentages (55% ± 4, 43% ± 2, and 42% ± 2, respectively) of C-fos activated neurons that were Gly/GABA increased significantly as compared with control (10 ± 1 and 25% ± 2). The increase in the total number of C-fos activated Gly/GABA neurons was present primarily in the superficial dorsal horn (laminae I and II; control: 9%; CFA 4 days: 56%; SNI 2 weeks: 42%). This increase in C-fos activation of Gly/GABA neurons occurred without significant changes in the total number of C-fos activated neurons, and without any significant changes in the mechanical thresholds in the hind paws after capsaicin injection. The results showed that one-sided chronic pain, especially inflammation, significantly increases the C-fos activation pattern of spinal Gly/GABA neurons on the other side of the spinal cord. This further underlines the existence of a dynamic interaction between ipsi- and contralateral spinal neurons in the processing of nociceptive information.

摘要

越来越多的证据表明,身体一侧的疼痛传递会受到另一侧疼痛状态的影响。我们通过研究辣椒素注射到大鼠同侧后爪后,脊髓甘氨酸能和 GABA 能(Gly/GABA)神经元的激活模式(使用 C-fos 标记)来研究这种现象。这些大鼠之前已经在对侧后爪接受了急性或慢性疼痛刺激预处理(急性:辣椒素,完全弗氏佐剂(CFA)1.5 小时;慢性炎症:CFA 20 小时和 4 天;神经病理性: spared nerve injury (SNI) 2 周),或者没有预处理(对照)。为此,我们将 GlyT2 和 GAD67 mRNA 探针的荧光原位杂交与荧光 C-fos 免疫组织化学相结合。我们发现,在 CFA 炎症(4 天)、sham-SNI 或 SNI 神经病理性疼痛预处理的大鼠中,辣椒素注射后 C-fos 激活神经元的数量(分别为 27±3、21±2 和 21±2)和百分比(分别为 55%±4、43%±2 和 42%±2)与对照相比显著增加。与对照相比,浅层背角(I 和 II 层;对照:9%;CFA 4 天:56%;SNI 2 周:42%)中 C-fos 激活的 Gly/GABA 神经元总数的增加更为显著。这种 C-fos 激活的 Gly/GABA 神经元的增加主要发生在浅层背角(I 和 II 层;对照:9%;CFA 4 天:56%;SNI 2 周:42%)。这种脊髓 Gly/GABA 神经元的 C-fos 激活增加与 C-fos 激活神经元总数的显著变化无关,并且在辣椒素注射后后爪的机械阈值也没有任何显著变化。结果表明,单侧慢性疼痛,特别是炎症,显著增加了对侧脊髓中脊髓 Gly/GABA 神经元的 C-fos 激活模式。这进一步强调了 ipsi- 和 contralateral 脊髓神经元在处理伤害性信息时存在动态相互作用。

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