Dexmedetomidine alleviates diabetic neuropathic pain by inhibiting microglial activation via regulation of miR618/P2Y12 pathway

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 luciferasereporter assay was used to verify microRNA (miR)-337 binding to Rap1A mRNA. Reverse transcriptionpolymerase 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 P2Y12levels (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

Effect of rPMS on N-type calcium channel in rats with neuropathic pain

“…Neuropathic pain (NP) is pain caused by pathological changes in the somatosensory nervous system, and may be associated with common diseases such as postherpetic neuralgia, trigeminal neuralgia, painful radiculopathy, diabetic neuropathy, HIV infection, lepriasis, amputation, peripheral nerve injury, and apoplexia [1]. Although the global prevalence of NP is 1.5 -8 % [2], effective treatments are absent owing to limited knowledge about the molecular mechanism of NP in the study circle [3]. Repetitive peripheral magnetic stimulation (rPMS) produces stimulation on the muscles, nerves, or spinal cord root [4] in a safe and minimally invasive way [5].…”