MicroRNA-124 and microRNA-146a both attenuate persistent neuropathic pain induced by morphine in male rats.

We have recently reported that a short course of morphine, starting 10 days after sciatic chronic constriction injury (CCI), prolonged the duration of mechanical allodynia for months after morphine ceased. Maintenance of this morphine-induced persistent sensitization was dependent on microglial reactivity and Toll-like receptor 4 signaling. Given that microRNAs (miRNAs) such as miR-124 and miR-146a possess the ability to modulate such signaling, we directly compared their function in this model. We found that both miRNAs reversed established allodynia in our model of morphine-induced persistent sensitization. The efficacy of miR-124 and miR-146a were comparable, and in both cases allodynia returned within hours to days of miRNA dosing conclusion. Our findings demonstrate that miRNAs targeting Toll-like receptor signaling are effective in reversing neuropathic pain, which underscores the clinical potential of these non-coding RNAs.