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.

Effects of laryngeal mask ventilation combined with continuous nerve block analgesia on postoperative lung infection in elderly patients undergoing the lower extremity orthopedics surgery / 中华老年医学杂志

Objective To investigate effects of laryngeal mask ventilation combined with continuous nerve block analgesia versus the endotracheal intubation under general anesthesia on postoperative lung infection in elderly patients undergoing orthopedic surgery,so as to provide a theoretical basis for a reasonable anesthesia method.Methods A total of 180 elderly patients undergoing lower extremity orthopedic surgery at our hospital from January 2016 to December 2016 were enrolled and randomly divided into two groups.The control group (n =90) were treated with endotracheal intubation under general anesthesia and intravenous analgesia after the operation,and the observation group (n =90)received the ultrasound-guided continuous nerve block analgesia in spontaneous respiration with laryngeal mask ventilation.The anesthetic dosage,awakening time,visual analogue scale(VAS)scores,and incidence of lung infections at 7 days after surgery were compared between the two groups.Pathogenic strains causing lung infections were isolated and identified.Results The anesthetic dosage was lower in the observation group than in the control group(P ＜ 0.05).The awaking time was shorter in the observation group than in the control group[(22.4±4.4) min vs.(34.1±8.5)min,P ＜0.05].The VAS scores under postoperative exercise were lower in the observation group than in the control group(P ＜0.05).The adverse reaction rate after surgery was lower in the observation group than in control group(3.3％ or 3/90 cases vs.41.1％ or 37/90 cases,P ＜0.05).The incidence of lung infections at 7 days after surgery was lower in the observation group than in the control group(3.3％ or 3/90 cases vs.11.1％ or 10/90 cases,P＜0.05).Ten pathogenic strains were isolated from control group,of which 9 strains were gram-negative bacteria,accounting for 90.0％.Three pathogenic strains were isolated from the observation group,of which 2 strains were gram-negative bacteria,accounting for 66.7％.Conclusions Laryngeal mask ventilation combined with continuous nerve block analgesia can reduce the anesthetic dosage,shorten the awaking time,provide a better analgesic effect and decrease the incidence of lung infections in elderly patients undergoing lower extremity orthopedics.The main pathogenic bacteria are gram-negative bacteria.