Upregulation of miR-22-3p Alleviates Hyperalgesia and Neuroinflammation Caused by Migraine.

Objective: Migraines profoundly impact patients' quality of life. This study seeks to investigate the relationship between dysregulated miR-22-3p and the neuroinflammation and central sensitization associated with migraine.

Methods: Initially, the level of miR-22-3p in migraine patients were analyzed using RT-qPCR. Subsequently, a migraine model was established by administering nitroglycerin (NTG) to mice. To modulate the levels of miR-22-3p within this model, agomir was utilized. Following this intervention, mechanical and thermal pain sensitivity were evaluated by Von Frey filament and radiant heat. The levels of c-Fos, CGRP, TNF-α, IL-1β, and IL-6 in trigeminal nucleus caudalis (TNC) were detected by RT-qPCR and ELISA. Furthermore, dual luciferase reporting assays were conducted to ascertain whether miR-22-3p could target KLF6. Moreover, the influence of KLF6 on inflammatory cytokines and central sensitization were further studied.

Results: miR-22-3p was significantly reduced in migraine patients and NTG mice. In animals, overexpression of miR-22-3p significantly alleviated hyperalgesia and neuroinflammation induced by NTG. Following the overexpression of miR-22-3p, we observed an increase in thermal withdrawal latency, paw mechanical threshold, and periorbital mechanical threshold. Conversely, levels of c-Fos, CGRP, TNF-α, IL-1β, and IL-6 exhibited a significant reduction. We found that miR-22-3p can inhibit KLF6 expression. Additionally, further findings indicated that the suppression of KLF6 resulted in decreased pain sensitivity along with diminished expression of c-Fos, CGRP, TNF-α, IL-1β, and IL-6.

Conclusion: In the context of migraine, miR-22-3p may play a pivotal role in mitigating neuroinflammation and alleviating central sensitization through the inhibition of KLF6.