rno-miR-199a-3p-Nedd4 signaling regulates mast cell-dependent peripheral sensitization in osteoarthritis pain.

PURPOSE: Acupoints are fundamental to the efficacy of acupuncture. When the body is diseased, the pressure pain threshold (PPT) of the corresponding acupoints typically exhibits significant changes. Clinically, selecting acupoints with marked PPT changes often enhances therapeutic efficacy. Mast cells are involved in changes in the PPT at acupoints, but the regulatory mechanism remains unclear. We aimed to identify microRNAs (miRNAs) that regulate mast cells to elucidate the mechanisms underlying PPT changes, thereby guiding clinical acupuncture practice.

METHODS

We evaluated changes in PPT and differentially expressed miRNAs at the ST36 acupoint in a rat model of knee osteoarthritis. miRNA agonists and antagonists were injected to observe changes in the PPT at the ST36 acupoint. Subsequently, the functions of differentially expressed miRNA in regulating degranulation and their possible targets of action were evaluated using in vitro and in vivo experiments.

RESULTS

PPT decreased in knee osteoarthritis (KOA) rats, accompanied by increased degranulation of local skin mast cells. rno-miR-199a-3p played a key role in this process. Overexpression of rno-miR-199a-3p increased mast cell degranulation. Furthermore, the overexpression of neural precursor cell expressed developmentally down-regulated 4 (Nedd4) is suppressed by rno-miR-199a-3p, which modulated mast cells.

CONCLUSION

Pathological changes in the body lead to changes in the PPT, manifested by altered local pain thresholds and mast cell degranulation. rno-miR-199a-3p targets Nedd4, leading to mast cell degranulation, which probably underlies this mechanism.