Zhu Yi, Sun Mei, Liu Peng, Shao Weidong, Xiong Ming, Xu Bo
Department of Anesthesiology, General Hospital of The Southern Theater Command of PLA, Guangzhou, China.
Department of Burns and Plastic Surgery, General Hospital of The Southern Theater Command of PLA, Guangzhou, China.
Korean J Pain. 2022 Oct 1;35(4):423-432. doi: 10.3344/kjp.2022.35.4.423.
The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 () which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting and cause the effects to CPSP.
To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORT™ dual luciferase assay was taken to verify whether miR-339-5p could act on as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats' amygdala were tested, and the expressions of miR-339-5p in each group of rats' amygdalas were also measured.
Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups ( < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups ( < 0.050). miR-339-5p acts on 3'UTR and take MOR mRNA as a target.
Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting . This regulatory pathway maybe an important molecular mechanism of CPSP.
杏仁核中μ-阿片受体(MOR)表达降低可能是慢性术后疼痛(CPSP)的关键分子。已知在应激大鼠模型的杏仁核中,miR-339-5p表达增加。通过RNAhybrid分析,miR-339-5p可直接靶向编码MOR的阿片受体μ1()。因此,作者推测miR-339-5p可通过靶向调节MOR的表达,并对CPSP产生影响。
为模拟围手术期短期应激,建立了围手术期应激延长切口诱导的疼痛超敏反应而不改变基础疼痛感知的大鼠模型。采用pmiR-RB-REPORT™双荧光素酶测定法验证miR-339-5p是否可作为靶点作用于。检测大鼠血清糖皮质激素水平。检测每组大鼠杏仁核中MOR、GFAP和pERK1/2的差异表达,并测定每组大鼠杏仁核中miR-339-5p的表达。
围手术期应激延长了切口疼痛的恢复时间。与其他组相比,应激+切口(S+IN)组大鼠杏仁核中MOR的表达显著下调(<0.050)。与其他组相比,S+IN组大鼠杏仁核中miR-339-5p显著上调(<0.050)。miR-339-5p作用于3'UTR并以MOR mRNA为靶点。
围手术期应激可增加miR-339-5p的表达,miR-339-5p可通过靶向导致MOR的表达降低。这种调节途径可能是CPSP的重要分子机制。