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http://dx.doi.org/10.3344/kjp.2022.35.4.423

Perioperative stress prolong post-surgical pain via miR-339-5p targeting oprm1 in the amygdala  

Zhu, Yi (Department of Anesthesiology, General Hospital of The Southern Theater Command of PLA)
Sun, Mei (Department of Anesthesiology, General Hospital of The Southern Theater Command of PLA)
Liu, Peng (Department of Burns and Plastic Surgery, General Hospital of The Southern Theater Command of PLA)
Shao, Weidong (Department of Anesthesiology, General Hospital of The Southern Theater Command of PLA)
Xiong, Ming (Department of Anesthesiology and Peri-Operative Medicine, New Jersey Medical School)
Xu, Bo (Department of Anesthesiology, General Hospital of The Southern Theater Command of PLA)
Publication Information
The Korean Journal of Pain / v.35, no.4, 2022 , pp. 423-432 More about this Journal
Abstract
Background: 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 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: 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-REPORTTM dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 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. Results: 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 (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3'UTR and take MOR mRNA as a target. Conclusions: Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.
Keywords
Amygdala; Glucocorticoids; MicroRNAs; Models, Animal; Pain Perception; Pain, Postoperative; Physiopathology; Receptors, Opioid, mu; Stress, Physiological;
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