Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Dexmedetomidine alleviates diabetic neuropathic pain by inhibiting microglial activation via regulation of miR-618/P2Y12 pathway

Jiannan Song¹, Shan Cong¹, Yan Qiao²

¹Department of Anesthesiology, Chifeng Municipal Hospital; ²Department of Neurology, Chifeng Municipal Hospital, Chifeng City, Inner Mongolia Autonomous Region, 024000, China.

For correspondence:- Yan Qiao Email: qiaoyan12300@163.com Tel:+864768365914

Accepted: 27 December 2020 Published: 31 January 2021

Citation: Song J, Cong S, Qiao Y. Dexmedetomidine alleviates diabetic neuropathic pain by inhibiting microglial activation via regulation of miR-618/P2Y12 pathway. Trop J Pharm Res 2021; 20(1):61-67 doi: 10.4314/tjpr.v20i1.10

© 2021 The authors.
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Abstract

Purpose: To investigate the effect of dexmedetomidine on streptozotocin (STZ)-induced diabetic neuropathy pain (DNP) in rats and elucidate its mechanism of action.

Methods: The DNP rat model was established by injecting STZ (70 mg/kg) following dexmedetomidine treatment. Next BV-2 cells were stimulated using lipopolysaccharide (LPS, 200 ng/mL) and then administered 20 μM dexmedetomidine. Blood glucose levels, body weight, and paw withdrawal threshold (PWT) were measured once a week in DNP rats. Transfection was performed, and luciferase reporter assay was used to verify microRNA (miR)-337 binding to Rap1A mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the levels of miR-618 and P2Y12 while the protein levels of P2Y12 and ionized calcium-binding adaptor molecule 1 (IBA-1) were determined by western blot analysis.

Results: Dexmedetomidine treatment significantly increased PWT (p < 0.01) in DNP rats and decreased miR-618 expression (p < 0.01) but increased P2Y12 expression (p < 0.01) in the spinal cord of DNP rats. Luciferase reporter assay data showed that the presumed binding site of miR-618 is located in the 3′-untranslated regions of P2Y12. MiR-618 overexpression significantly reduced P2Y12 levels (p < 0.01). Dexmedetomidine upregulated P2Y12 expression (p < 0.01) but decreased IBA-1 expression (p < 0.01).

Conclusion: Dexmedetomidine application attenuates DNP by inhibiting microglial activation via the regulation of miR-618/P2Y12 pathway. This finding provides a potential therapeutic strategy for DNP management.

Keywords: Dexmedetomidine, Diabetic neuropathy pain, Paw withdrawal threshold, Calcium-binding adaptor molecule 1, MiR-618, P2Y12