miR-26a-5p alleviates CFA-induced chronic inflammatory hyperalgesia through Wnt5a/CaMKII/NFAT signaling in mice.

BACKGROUND: Inflammation often leads to the occurrence of chronic pain, and many miRNAs have been shown to play a key role in the development of inflammatory pain. However, whether miR-26a-5p relieves pain induced by inflammation and its possible mechanism are still unclear. METHODS: The complete Freund's adjuvant (CFA)-induced inflammatory pain mouse model was employed. Intrathecal or subcutaneous injection of miR-26a-5p agomir was performed after modeling to study its antinociceptive effect and the comparison of different administration methods. Bioinformatics analysis of miRNAs was performed to study the downstream mechanisms of miR-26a-5p. HE staining, RT-qPCR, Western blotting, and immunofluorescence were used for further validation. RESULTS: A single intrathecal and subcutaneous injection of miR-26a-5p both reversed mechanical hypersensitivity and thermal latency in the left hind paw of mice with CFA-induced inflammatory pain. HE staining and immunofluorescence studies found that both administrations of miR-26a-5p alleviated inflammation in the periphery and spinal cord. Bioinformatics analysis and dual-luciferase reporter gene analysis identified Wnt5a as a direct downstream target gene of miR-26a-5p. Wnt5a was mainly expressed in neurons and microglia in the spinal cord of mice with inflammatory pain. Intrathecal injection of miR-26a-5p could significantly reduce the expression level of Wnt5a and inhibit the downstream molecules of noncanonical Wnt signaling Camk2/NFAT, inhibiting the release of spinal cord inflammatory factors and alleviating the activation of microglia. In addition, miR-26a-5p could also inhibit lipopolysaccharide (LPS)-stimulated BV2 cell inflammation in vitro through a noncanonical Wnt signaling pathway. CONCLUSIONS: miR-26a-5p is a promising therapy for CFA-induced inflammatory pain. Both intrathecal and subcutaneous injections provide relief for inflammatory pain. miR-26a-5p regulated noncanonical Wnt signaling to be involved in analgesia partly through antineuroinflammation, suggesting a pain-alleviating effect via noncanonical Wnt signaling pathway in the CFA-induced inflammatory pain model in vivo.

Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia.

BACKGROUND: Propofol is a safe and effective intravenous anesthetic that is widely used for the induction and maintenance of anesthesia during surgery. However, the mechanism by which propofol exerts its anesthetic effect remains unknown. The rapid onset of phosphorylation modifications coincides with that of propofol anesthesia. METHODS: Propofol-anesthetized rat models were built and phosphorylated proteins in the thalamus, hippocampus and frontal lobe were enriched the to analyze the changes in these phosphoproteins after propofol anesthesia. RESULTS: Sixteen of these phosphoprotein spots were successfully identified using MALDI-TOF MS and a subsequent comparative sequence search in the Mascot database. Of these proteins, keratin 18 and the tubulin 2c chain are cytoskeletal proteins; keratin 18 and gelsolin are relevant to alcohol drowsiness. Based on Western blot analysis, we also confirmed that the phosphorylation of these proteins is directly induced by propofol, indicating that propofol anesthesia may be relevant to cytoskeletal proteins and alcohol drowsiness. CONCLUSIONS: These identified propofol-induced phosphorylations of proteins provide meaningful contributions for further studying the anesthetic mechanism of propofol.

[Prophylactic effect of acupuncture on nausea and vomiting after laparoscopic operation].

OBJECTIVE: To explore the prophylactic effect of acupuncture Neiguan (PC 6) on nausea and vomiting after laparoscopic operation. METHODS: One hundred patients with laparoscopic gastrointestinal operation were randomly divided into an acupuncture group and a control group, 50 patients in each group. The operation was carried out with the combined infusion and inhalation anesthesia. The patients in the acupuncture group were being punctured at bilateral Neiguan (PC 6) before anesthesia and during the operation. The needles were extracted after operation, and the acupoints were covered with opaque tape. In contrast, the patients in the control group only accepted tape covering without acupuncture. After operation, all patients were given the self-controlled intravenous analgesia, and followed up at 6 h, 12 h, 24 h, 48 h for recording the incidence rate of the nausea, retching and vomiting, then scoring with VAS. RESULTS: At 6 h, 12 h, 24 h, 48 h after operation, in the acupuncture group, the incidence rates of the nausea were 12.0%, 6.0%, 6.0% and 2.0%, and the incidence rates of the retching were 0, 0, 2.0% and 2.0%, respectively; in the control group, the incidence rates of the nausea were 28.0%, 20.0%, 12.0% and 2.0%, and the incidence rates of the retching were 2.0%, 6.0%, 2.0% and 0, respectively. At 6 h, 12 h after operation, the incidence rates of the nausea and retching in the acupuncture group were lower than those of the control group (P < 0.05, P < 0.001). The vomiting was not happened in both groups. There was no difference between the two groups according to the scoring with VAS. CONCLUSION: Acupuncturing at Neiguan (PC 6) can reduce the incidence rates of the patients' nausea and retching after laparoscopic operation, especially in 24 h.