Plasma-derived exosomal miR-144-3p targeting IL-1β is involved in pressure pain threshold regulation at PC6 acupoint in myocardial ischemia rats

As an auxiliary therapy, acupuncture is effective in ameliorating myocardial ischemia (MI). Selecting correct acupoints is widely acknowledged to be key for therapeutic effects of acupuncture, and traditional acupuncturists believe that selecting acupoints whose pressure pain threshold (PPT) change with disease, for instance selecting PC6 (Neiguan) when MI occurs, usually leads to better therapeutic effects. In this study, we aimed to identify the molecular mechanism of PPT regulation at PC6 in MI rats.

Firstly, we established MI models by intraperitoneal injection of ISO and evaluated PPT changes and mast cell degranulation (MCD) at PC6 during MI. Then, we performed high-throughput sequencing and overlapped the differentially expressed miRNAs in plasma and skin tissue from the left PC6 (L-PC6). Through bioinformatics analysis and dual-luciferase reporter assays, we tried to find the downstream molecules of miRNA. Subsequently, miRNA agonists were injected intramusculally at L-PC6, and we paid attention to changes in PPT and MCD at L-PC6 as well as the relationship between local mast cells (MCs) and nerve axons.

PPT decreased and MCD increased at PC6 in MI rats and miR-144-3p is a key molecule in the induction of these phenomenon. Furthermore, miR-144-3p targeting Interleukin-1β (IL-1β) leads to local MCD, neurogenic inflammation and peripheral nociceptor hypersensitization, finally resulting in PPT change at PC6. Innovatively, our study also provides a new direction for investigating the relationship between MCs, PPT and sensitivity of acupoints, which is mediated by miR-144-3p.