系统地使用NIS-lncRNA反感性寡核酸可缓解神经病痛
Tolga Berkman1, Xiang Li1, Yingping Liang1
1Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark NJ07103, USA.
Neuroscience letters
|October 8, 2023
概括
对神经损伤特异的长非编码RNA抗意义寡核酸 (ASO) 进行全身治疗,有效地减少了小鼠的神经病痛. 这种方法为治疗慢性疼痛提供了一个有希望的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 反感性寡核酸 (ASO) 疗法是FDA批准用于神经疾病.
- 内ASO已显示在抑制脊髓根质 (DRG) 中神经损伤特异性长非编码RNA (NIS-lncRNA) 的有效性,提供长期的疼痛缓解.
- 慢性收缩损伤 (CCI) 后的神经病痛 (NP) 是一个重大的临床挑战.
研究的目的:
- 调查系统性NIS-lncRNA ASO给药在缓解CCI诱导的神经病痛方面的疗效.
- 确定系统性ASO治疗是否可以抑制NIS-lncRNA表达及其在DRG和脊髓的下游影响.
- 为了评估系统NIS-lncRNA ASO治疗后抗受体效应的持续时间和稳定性.
主要方法:
- 雄性小鼠接受了CCI或假手术,然后在手术后7天内进行一次皮下注射NIS-lncRNA ASO (1,000μg).
- 在行为测试中,评估了机械律,热过敏症,寒冷过敏症和自发疼痛.
- 量化实时RT-PCR和西部斑点测定在DRG和脊髓组织上进行,以测量基因和蛋白质表达.
主要成果:
- 系统性NIS-lncRNA ASO显著降低了机械全音,热过敏和冷过敏,从注射后14-21天开始,持续至少7天.
- 背部角中CCI诱导的自发疼痛和神经元/星细胞过活化在ASO给药28天后被阻止.
- 在DRG中,NIS-lncRNA ASO治疗减弱了CCI诱导的NIS-lncRNA及其标,C-C动机化学因子连接体2的增加.
结论:
- 系统性使用NIS-lncRNA ASO可对神经病痛产生稳定且持久的抗受体作用.
- 这种治疗策略显示出在治疗神经病痛性疼痛障碍方面具有临床应用的潜力.
- 通过系统管理的ASO向NIS-lncRNA代表了治疗疼痛的可行方法.
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