Spinal nerve transection-induced upregulation of SAP97 via promoting membrane trafficking of GluA1-containing AMPA receptors in the dorsal horn contributes to the pathogenesis of neuropathic pain.

Emerging evidence has implicated an important role of synapse-associated protein-97 (SAP97)-regulated GluA1-containing AMPARs membrane trafficking in cocaine restate and in contextual episodic memory of schizophrenia. Herein, we investigated the role of SAP97 in neuropathic pain following lumbar 5 spinal nerve transection (SNT) in rats. Our results showed that SNT led to upregulation of SAP97, enhanced the interaction between SAP97 and GluA1, and increased GluA1-containing AMPARs membrane trafficking in the dorsal horn. Microinjection of AAV-EGFP-SAP97 shRNA in lumbar 5 spinal dorsal horn inhibited SAP97 production, decreased SAP97-GluA1 interaction, reduced the membrane trafficking of GluA1-containing AMPARs, and partially attenuated neuropathic pain following SNT. Intrathecal injections of SAP97 siRNA or NASPM, an antagonist of GluA1-containing AMPARs, also partially reversed neuropathic pain on day 7, but not on day 14, after SNT. Spinal overexpression of SAP97 by AAV-EGFP-SAP97 enhanced SAP97-GluA1 interaction, increased the membrane insertion of GluA1-containing AMPARs, and induced abnormal pain in naïve rats. In addition, treatment with SAP97 siRNA or NASPM i.t. injection alleviated SNT-induced allodynia and hyperalgesia and exhibited a longer effect in female rats. Together, our results indicate that the SNT-induced upregulation of SAP97 via promoting GluA1-containing AMPARs membrane trafficking in the dorsal horn contributes to the pathogenesis of neuropathic pain. Targeting spinal SAP97 might be a promising therapeutic strategy to treatment of chronic pain.

Intensity-modulated radiotherapy, coplanar volumetric-modulated arc, therapy, and noncoplanar volumetric-modulated arc therapy in, glioblastoma: A dosimetric comparison.

OBJECTIVE: Advanced techniques such as volumetric-modulated arc therapy (VMAT) may reduce radiation damage and improve the quality of life for patients.We performed a study comparing dose distributions to the planning target volumes(PTVs) and other organs at risk (OARs) of intensity-modulated radiotherapy (IMRT),coplanar VMAT (coVMAT), and non-coplanar VMAT (ncVMAT). PATIENTS AND METHODS: 13 patients with GBM who had undergone postoperative radiotherapy were enrolled. Three plans for each patient were created, namely, IMRT, coVMAT, and ncVMAT. Prescription doses and normal-tissue constraints were identical for these three plans. The dosimetric differences of target dose distribution, conformity index (CI), homogeneity index (HI), the gradient index (GI), dose of OARs, monitor units (MUs) and beam-on times among these three plans were investigated. RESULTS: These three techniques resulted in comparable maximum, minimum, and mean PTV doses. Small but insignificant differences were observed in GI,CI, and HI. Compared with IMRT, VMAT plans showed statistically significant reductions in the mean doses to the optic chiasm (P < 0.05). Compared with IMRT, VMAT techniques significantly reduced the number of MUs and less beam-on time than IMRT techniques (P ＜ 0.05). However, calculation times were significantly longer for ncVMAT and coVMAT plans at 12 and 12.3 min, versus 2.6 min for IMRT. Our study showed that IMRT or VMAT planning is feasible and efficient for patients with GBM.Compared to IMRT plans, ncVMAT or coVMAT plans showed similar PTV coverage and comparable OARs sparing. VMAT plans significantly reduces the mean doses to the optic chiasm than IMRT plans. CONCLUSION: There was no obvious superiority of ncVMAT over coVMAT in target coverage and sparing of OARs.Compared with IMRT, VMAT techniques significantly reduced the number of MUs and beam-on time but extended the calculation times.