Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.
Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.
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DOI：
10.1016/j.brainres.2009.06.043
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发表时间：
2009-08-25
期刊：
影响因子：
2.9
通讯作者：
Mao J
中科院分区：
文献类型：
--
作者：
Hernstadt H;Wang S;Lim G;Mao J
转运蛋白18 kDa（TSPO），以前称为外周苯二氮卓受体（PBR），主要位于线粒体外膜，并且在类固醇生成、免疫调节、细胞存活和增殖中起重要作用。先前的研究已经显示TSPO在神经病理学中以及在损伤的神经中的中枢表达增加。TSPO还涉及伤害感受的调节。在本研究中，我们研究的假设，TSPO是参与启动和维持炎性疼痛使用大鼠模型完全弗氏佐剂（CFA）诱导的单关节炎的胫跗关节。在CFA诱导的关节炎后第1、7和14天，使用Iba-1（小胶质细胞）、NeuN（神经元）、抗胶质纤维酸性蛋白、GFAP（星形胶质细胞）和抗PBR（TSPO）进行免疫组织化学。CFA诱导的单关节炎大鼠表现出机械异常性疼痛和热痛觉过敏的同侧后爪，这与增加TSPO表达在同侧板层I-II在所有实验日。在第7天和第14天，同侧背角中的Iba-1表达也增加。此外，TSPO与Iba-1，GFAP和NeuN在脊髓背角内共定位。TSPO激动剂Ro 5 -4864，鞘内给药，剂量依赖性地延缓或预防CFA诱导的单关节炎大鼠的机械异常性疼痛和热痛觉过敏的发展。这些发现提供了证据，脊髓TSPO参与大鼠炎性疼痛行为的发展和维持。因此，脊髓TSPO可能作为一种补充疗法，以减少炎性疼痛的中心目标。
Translocator protein 18kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund’s Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on day 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral lamina I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Day 7 and 14. Moreover, TSPO was co-localized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.
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影响因子：
3.3
作者：
BESSLER, H;WEIZMAN, R;DJALDETTI, M
通讯作者：
DJALDETTI, M
DOI：
10.1016/s0960-0760(99)00056-4
发表时间：
1999-04-01
影响因子：
4.1
作者：
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通讯作者：
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影响因子：
7.4
作者：
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影响因子：
3.6
作者：
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通讯作者：
Malcangio, Marzia
影响因子：
4.1
作者：
Dhir, A.;Kulkarni, S. K.
通讯作者：
Kulkarni, S. K.