Inhibition of MicroRNA-15a/16 Expression Alleviates Neuropathic Pain Development through Upregulation of G Protein-Coupled Receptor Kinase 2

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

Comparison of the effects of different doses of methylprednisolone therapy for children with severe hand,foot and mouth disease / 中国基层医药

Objective To compare the clinical effects of different doses of methylprednisolone therapy for children with severe hand,foot and mouth disease (HFMD).Methods According to different dosage methods, 240 children with severe HFMD were divided into large dose group,medium dose group and small dose group,80 cases in each group.The three groups were given different doses of methylprednisolone infusion on the basis of conventional treatment:large dose group(5 ~10mg·kg· -1 d -1 ),medium dose group(3 ~5 mg·kg· -1 d -1 ),small dose group (1 ~2mg · kg · -1 d -1 ).Results The time of fever sustaining,panic ease,mechanical ventilation,duration of hypertension and heart rate recovery of the medium -dose group were (47.93 ±4.72)h,(45.54 ±2.42)h,(51.43 ± 6.85)h,(53.66 ±7.62)h,(52.45 ±7.84)h,which were significantly shorter than those of the small -dose and large -dose group(all P 0.05 ). Conclusion Medium dose of methylprednisolone in the treatment of children with severe HFMD has significant effect and less adverse reactions,which is worthy of promotion.