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米诺环素通过抑制神经元 ERK 磷酸化显著减轻急性内脏痛觉。

Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation.

机构信息

Department of Anatomy, Kyung Hee University, Seoul, South Korea.

出版信息

Mol Pain. 2012 Feb 24;8:13. doi: 10.1186/1744-8069-8-13.

DOI:10.1186/1744-8069-8-13
PMID:22364340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3342906/
Abstract

BACKGROUND

Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 μl, i.p.).

RESULTS

Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid-induced nociception (0-60 minutes post-injection) and the enhancement in the number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid injection. Also, the expression of spinal phosphorylated extracellular signal-regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre-administration. Interestingly, intrathecal introduction of PD98059, an ERK upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain responses.

CONCLUSIONS

These results demonstrate that minocycline effectively inhibits acetic acid-induced acute abdominal nociception via the inhibition of neuronal p-ERK expression in the spinal cord, and that minocycline may have therapeutic potential in suppressing acute abdominal pain.

摘要

背景

米诺环素通过抑制小胶质细胞激活和突触后电流来预防神经性和炎性疼痛的发展。但是,米诺环素如何消除急性内脏疼痛尚不清楚。本研究探讨了米诺环素在腹腔内(i.p.)给予生理盐水或米诺环素 1 小时后(1.0%,250μl,i.p.)是否对醋酸诱导的急性腹痛有任何镇痛作用。

结果

米诺环素(4、10 或 40mg/kg)显著减少了醋酸诱导的疼痛(注射后 0-60 分钟)和醋酸注射引起的 T5-L2 脊髓中 c-Fos 阳性细胞数量的增加。此外,预先给予米诺环素可减少由醋酸诱导的脊髓磷酸化细胞外信号调节激酶(p-ERK)的表达。有趣的是,鞘内引入 ERK 上游激酶抑制剂 PD98059 可显著阻断醋酸刺激的疼痛反应。

结论

这些结果表明,米诺环素通过抑制脊髓神经元 p-ERK 的表达,有效抑制了醋酸诱导的急性腹痛,米诺环素可能具有抑制急性腹痛的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/df6e7e615627/1744-8069-8-13-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/da7b6bded5eb/1744-8069-8-13-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/1933ab2ee67f/1744-8069-8-13-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/5b5085c35237/1744-8069-8-13-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/b44c44b2b8cf/1744-8069-8-13-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/df6e7e615627/1744-8069-8-13-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/da7b6bded5eb/1744-8069-8-13-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/1933ab2ee67f/1744-8069-8-13-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/5b5085c35237/1744-8069-8-13-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/b44c44b2b8cf/1744-8069-8-13-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa5/3342906/df6e7e615627/1744-8069-8-13-5.jpg

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