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.

Effect of hydrogen sulifde on the expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells withHelicobacter pylori infection / 中南大学学报(医学版)

Objective: To investigate the effect of hydrogen sulifde (H2S) on the expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells withHelicobacter pylori (H. pylori) infection and to explore its mechanism on gastric mucosa inlfammation caused byH. pylori. Methods: GES-1 cells were cultured for 24 h and divided into a control group (neitherH. pylori nor NaHS), anH. pylori group, a NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 μmol/L NaHS), andH. pylori + NaHS group (which was further divided into 4 groups at 50, 100, 200, or 400 μmol/L NaHS). Each group was then cultured for 3, 6, or 12 h. The expression of CSE, NF-κB, and IL-8 mRNA was measured by RT-PCR, and their correlation was analyzed. Results: The expression of CSE, NF-κB, and IL-8 mRNA in GES-1 cells in theH. pylori group was higher than that in the control group. The expression of CSE in the 200 μmol/L NaHS group and 400 μmol/L NaHS group was lower than that of the control group (P0.05). The expression of CSE, NF-κB, and IL-8 mRNA in all groups of NaHS,H. pylori + 200 μmol/L NaHS group, andH. pylori + 400 μmol/L NaHS group was lower than that in theH. pylori group (P Conclusion:H. pylori can induce NF-κB and IL-8 mRNA expression and upregulate CSE mRNA expression. At 200 and 400 μmol/L, NaHS can suppressH. pylori-induced NF-κB and IL-8 mRNA expression and ameliorate the morphology ofH. pylori-induced GES-1 injury, which may protect gastric epithelial cells byH. pylori infection.