Let-7b-5p promotes electroacupuncture tolerance by downregulating Penk1 gene in CFA-induced inflammatory nociception rats

Background: Studies showed that increased let-7b-5p microRNA during repeated electroacupuncture (FA) treatment was associated the formation of EA tolerance, which manifested as gradually decreased nociceptive threshold. Proenkephalin (PENK) is the precursor of enkephalin which is a pivot neuropeptide responsible for the decreased nociceptive threshold in EA. The aim of this study was to evaluate the relationship between let-7b-5p and PENK in EA tolerance. Methods: The target gene of let-7b-5p microRNA was determined through the dual-luciferase reporter assay in cortical neurons. Seventy-two Sprague Dawley rats received a combination of EA and intracerebroventricular injection of microRNA (let-7b-5p agomir, antagomir or their controls). The nociceptive thresholds were assessed with radiant heat tail-flick method. PENK and let-7b-5p were measured with Western Blot and qPCR, respec- tively, after administration of let-7b-5p agomir, antagomir, and their controls at day 1, 4 and 7. Results: Let-7b-5p targeted the 3' untranslated region of Penkl. The nociceptive thresholds in Let-7b-5p agomir + EA group were decreased (p < 0.05) compared with those in Let-7b-5p antagomir + EA group at day 1 to 7. Compared with Let-7b-5p agomir + EA group, the expression level of PENK in Let-7b-5p antagomir + EA group was increased at days 1, 4, and 7 (p < 0.05) Conclusion: Let-7b-5p may be a new potential target for decreasing the EA tolerance effect and facilitating the application of EA in treating chronic nociception of patients.