MicroRNA-146a attenuates the development of morphine analgesic tolerance in a rat model.

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. [ABSTRACT FROM AUTHOR]