Knockdown of Synaptic Scaffolding Protein Homer 1b/c Attenuates Secondary Hyperalgesia Induced by Complete Freund's Adjuvant in Rats
Knockdown of Synaptic Scaffolding Protein Homer 1b/c Attenuates Secondary Hyperalgesia Induced by Complete Freund's Adjuvant in Rats
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突触支架蛋白 Homer 1b/c 的敲低可减轻弗氏完全佐剂诱导的大鼠继发性痛觉过敏
DOI：
10.1213/ane.0b013e31822c0b98
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发表时间：
2011-10
影响因子：
5.7
通讯作者：
Zhao, Zhi-Qi
中科院分区：
文献类型：
--
作者：
Yao, Yong-Xing;Jiang, Zhen;Zhao, Zhi-Qi
背景技术背景：以往的研究表明，Homer 1b/c，突触后分子支架蛋白，结合和簇集在神经元突触的代谢型谷氨酸受体，在代谢型谷氨酸受体的信号转导过程中具有重要作用。在本研究中，我们调查了Homer 1b/c在完全弗氏佐剂（CFA）诱导的继发性痛觉过敏中的可能参与。方法：Wistar大鼠左后踝关节注射CFA建立慢性炎症模型。在炎症发作后5 - 8天鞘内给予Homer 1b/c反义或错义寡核苷酸（反义，10 g/10 L、5 g/10 L或2.5 g/10 L，每天一次;错义，10 g/10 L）。测定鞘内给药前后大鼠对机械刺激或热刺激的缩足阈和缩足潜伏期。应用免疫组化技术检测脊髓Homer 1b/c的表达和分布。结果：CFA注射后24小时内诱导出机械性异常性疼痛和热痛觉过敏，并维持2周以上。Homer 1b/c的表达在炎症后7天达到最高水平，并在第28天恢复到基线水平。鞘内注射Homer 1b/c反义寡核苷酸可显著降低脊髓Homer 1b/c蛋白的表达。此外，Homer 1b/c反义寡核苷酸给药在第2 - 5天减弱了继发性机械超敏反应，在第3 - 4天降低了热超敏反应。错义寡核苷酸对超敏反应和Homer 1b/c的表达没有影响。Homer 1b/c反义寡核苷酸不影响未处理大鼠的机械和热反应或自发活动。结论：这些新的结果表明，脊髓中的Homer 1b/c有助于维持CFA诱导的继发性痛觉过敏，并表明Homer 1b/c可能是疼痛治疗的新靶点。
BACKGROUND: Previous studies have demonstrated that Homer 1b/c, a postsynaptic molecular scaffolding protein that binds and clusters metabotropic glutamate receptors at neuronal synapses, has an important role in the metabotropic glutamate receptor signaling process. In the current study, we investigated the possible involvement of Homer 1b/c in secondary hyperalgesia induced by complete Freund's adjuvant (CFA). METHODS: Chronic inflammation was induced by injecting CFA into the left hind ankle of Wistar rats. Homer 1b/c antisense or missense oligonucleotides were intrathecally administrated (antisense, 10 &mgr;g/10 &mgr;L, 5 &mgr;g/10 &mgr;L, or 2.5 &mgr;g/10 &mgr;L, once a day; missense, 10 &mgr;g/10 &mgr;L) from 5 to 8 days after the onset of inflammation. The withdrawal threshold and withdrawal latency to mechanical or thermal stimuli were determined before and after the intrathecal administration. The expression and distribution of Homer 1b/c were examined in the spinal cord using immunological techniques. RESULTS: Mechanical allodynia and thermal hyperalgesia were induced within 24 hours and maintained for >2 weeks after the CFA injection. The expression of Homer 1b/c reached the highest level 7 days after inflammation and returned to baseline at day 28. Intrathecal administration of Homer 1b/c antisense oligonucleotides markedly reduced the expression of Homer 1b/c protein in the spinal cord. Additionally, administration of Homer 1b/c antisense oligonucleotides attenuated secondary mechanical hypersensitization on days 2 to 5 and reduced thermal hypersensitization on days 3 to 4. There were no effects of missense oligonucleotides on hypersensitization and the expression of Homer 1b/c. In the naïve rats, Homer 1b/c antisense oligonucleotides did not affect the mechanical and thermal responses or locomotor activity. CONCLUSIONS: These novel results demonstrate that Homer 1b/c in the spinal cord contributes to the maintenance of secondary hyperalgesia induced by CFA and suggest that Homer 1b/c may be a novel target for pain therapy.
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DOI：
10.1042/bj3410795
发表时间：
1999-08
期刊：
The Biochemical journal
影响因子：
--
作者：
F. Ciruela;M. Soloviev;R. Mcilhinney
通讯作者：
F. Ciruela;M. Soloviev;R. Mcilhinney
DOI：
10.1523/jneurosci.20-23-08710.2000
发表时间：
2000-12
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
F. Ango;J. Pin;J. Tu;B. Xiao;P. Worley;J. Bockaert;L. Fagni
通讯作者：
F. Ango;J. Pin;J. Tu;B. Xiao;P. Worley;J. Bockaert;L. Fagni
影响因子：
2.5
作者：
Shiraishi, Y;Mizutani, A;Furuichi, T
通讯作者：
Furuichi, T
影响因子：
3.5
作者：
Ango, F;Robbe, D;Fagni, L
通讯作者：
Fagni, L
DOI：
10.1523/jneurosci.19-19-08389.1999
发表时间：
1999-10
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Y. Shiraishi;A. Mizutani;H. Bito;K. Fujisawa;S. Narumiya;K. Mikoshiba;T. Furuichi
通讯作者：
Y. Shiraishi;A. Mizutani;H. Bito;K. Fujisawa;S. Narumiya;K. Mikoshiba;T. Furuichi