Background: Morphine plays an irreplaceable role in relieving severe pain clinically, while long-term medication inevitably leads to drug resistance. MicroRNA (miR) 146a has been reported to be a negative regulator in the process of morphine-tolerance formation. This study aimed to investigate how miR-146a affects the development of morphine analgesic tolerance.

Methods: The morphine-tolerance rat model was established by means of one-week continuous morphine administration. Paw withdrawal latency test was performed every day, and spinal cord samples were dissected on the seventh day for Q-PCR and Western blotting to detect the expression level of miR-146a, and IRAK1/TRAF6 participated in TLR4 signaling pathway.

Results: The expression of miR-146 was significantly decreased in morphine-tolerant model. Also, overexpression of miR-146a reduced the resistance caused by morphine, followed by the down-regulation of IRAK1/TRAF6 in TLR4 pathway. The inhibition of miR-146a remarkably decreased paw withdrawal latency as well as increased the expression levels of TLR4 signaling pathway-related molecules, IRAK1 and TRAF6.

Conclusion: This study suggests that miR-146a attenuates morphine tolerance by inhibiting the expression of IRAK1/TRAF6 in TLR4 pathway, which could provide an essential experimental basis for the settlement of morphine resistance-associated matters.

背景：吗啡在减轻临床上的剧烈疼痛中起着不可替代的作用，而长期服用药物不可避免地导致耐药性。据报道，MicroRNA（miR）146a在吗啡耐受性形成过程中为负调节剂。这项研究旨在调查miR-146a如何影响吗啡镇痛耐受性的发展。

方法：通过连续一周的吗啡给药建立吗啡耐受大鼠模型。每天进行爪退缩潜伏期测试，并在第七天解剖脊髓样品进行Q-PCR和Western blotting检测miR-146a的表达水平，IRAK1 / TRAF6参与TLR4信号通路。

结果：吗啡耐受模型中miR-146的表达明显降低。同样，miR-146a的过表达降低了吗啡引起的耐药性，随后在TLR4途径中下调了IRAK1 / TRAF6。对miR-146a的抑制作用显着降低了爪缩回潜伏期，并提高了TLR4信号通路相关分子IRAK1和TRAF6的表达水平。

结论：本研究提示miR-146a通过抑制IRR1 / TRAF6在TLR4途径中的表达减弱了对吗啡的耐受性，这可能为解决吗啡抗性相关物质提供了重要的实验基础。