期刊
BRAIN RESEARCH
卷 1692, 期 -, 页码 9-11出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2018.04.038
关键词
TLR4; P2X7R; Danger signals; Priming; Opioid-induced hyperalgesia
资金
- American Pain Society Future Leaders in Pain Research Grants Program
- National Health and Medical Research Council CJ Martin Fellowship [1054091]
- American Australian Association Sir Keith Murdoch Fellowship
- NIH [DE021966, DA023132]
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. (C) 2018 Elsevier B.V. All rights reserved.
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