NR2B-Tyr phosphorylation regulates synaptic plasticity in central sensitization in a chronic migraine rat model.

BACKGROUND: Although the mechanism of chronic migraine (CM) is unclear, it might be related to central sensitization and neuronal persistent hyperexcitability. The tyrosine phosphorylation of NR2B (NR2B-pTyr) reportedly contributes to the development of central sensitization and persistent pain in the spinal cord. Central sensitization is thought to be associated with an increase in synaptic efficiency, but the mechanism through which NR2B-pTyr regulates synaptic participation in CM-related central sensitization is unknown. In this study, we aim to investigate the role of NR2B-pTyr in regulating synaptic plasticity in CM-related central sensitization. METHODS: Male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections to model recurrent trigeminovascular or dural nociceptor activation, which is assumed to occur in patients with CM. We used the von Frey test to detect changes in mechanical withdrawal thresholds, and western blotting and immunofluorescence staining assays were performed to detect the expression of NR2B-pTyr in the trigeminal nucleus caudalis (TNC). NR2B-pTyr was blocked with the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)-pyrazolo [3,4-d] pyrimidine (PP2) and the protein tyrosine kinase inhibitor genistein to detected the changes in calcitonin gene-related peptide (CGRP), substance P (SP), and the synaptic proteins postsynaptic density 95 (PSD95), synaptophysin (Syp), synaptotagmin1 (Syt-1). The synaptic ultrastructures were observed by transmission electron microscopy (TEM), and the dendritic architecture of TNC neurons was observed by Golgi-Cox staining. RESULTS: Statistical analyses revealed that repeated infusions of IS induced mechanical allodynia and significantly increased the expression of NR2B Tyr-1472 phosphorylation (pNR2B-Y1472) and NR2B Tyr-1252 phosphorylation (pNR2B-Y1252) in the TNC. Furthermore, the inhibition of NR2B-pTyr by PP2 and genistein relieved allodynia and reduced the expression of CGRP, SP, PSD95, Syp and Syt-1 and synaptic transmission. CONCLUSIONS: These data indicate that NR2B-pTyr might regulate synaptic plasticity in central sensitization in a CM rat model. The inhibition of NR2B tyrosine phosphorylation has a protective effect on threshold dysfunction and migraine attacks through the regulation of synaptic plasticity in central sensitization.

[Curative effect analysis on closed reduction and external fixator under local anesthesia for the treatment of intertrochanteric fracture in elderly patients with high-risk].

OBJECTIVE: To explore clinical efficacy of closed reduction and external fixation under local anesthesia for the treatment of high-risk elderly patients with intertrochanteric fracture. METHODS: From March 2013 to March 2015, 10 patients with intertrochanteric fractures treated with closing reduction and external fixator under local anesthesia were analyszed, including 4 males and 6 females, aged from 69 to 88 years old with an average of 75.2 years old. All fractures were caused by injury and classified to type I (5 cases), II (3 cases), and V (2 cases) according to Evans classification. According to American Society of Anesthesiologists (ASA), 6 cases were type III and 4 cases were type IV. Blood loss,operative time,hospital stays, postoperative complications, ambulation time and fracture healing time were observed, and Harris scoring were used to evaluate hip joint function. RESULTS: All patients were followed up from 3 to 23 months with an average of 13.1 months. One patient with chronic obstructive pulmonary disease died for non-operation reason at 4 months after operation, the other fractures were healed at stage I, the mean fracture healing time was 5.6 months. There were no coxa vara, lower limb venous thrombosis, loosen and remove of needle passage. The average operative time was 46 min, blood loss was (35.00 ± 8.46) ml without blood transfusion. One patient was occurred pulmonary infection and stent-tract infection on the 2 nd and 3 rd day after operation, and improved with active anti-infection and dressing change; the other patients gone to ground activity at 4.2 d after operation. The patients stayed hospital for 10.6 d on average. According to Harris scoring at final following-up, the total score was 83.42 ± 3.27, 3 cases obtained excellent results, 5 cases good and 1 case poor. CONCLUSION: Closed reduction and external fixation under local anesthesia in treating high-risk elderly patients with intertrochanteric fracture,which has advantages of shorter operative time, less blood loss, good recovery of postoperative function, is a safe, stable and economic method.