Key points Spinal cord dorsal horn srGAP3 (slit‐robo GTPase activating protein 3) increases in the initiation phase of neuropathic pain and decreases in the maintenance phase. However, Rac1 activity, which can be reduced by srGAP3, decreases in the initiation phase and increases in the maintenance phase. The increased srGAP3 in the initiation phase promotes new immature dendritic spines instigating neuropathic pain. Decreased srGAP3 in the maintenance phase enhances Rac1 activity facilitating maturation of dendritic spines and the persistence of neuropathic pain. SrGAP3 small interfering RNA can ameliorate neuropathic pain only when administrated in the initiation phase. The Rac1 inhibitor can ameliorate neuropathic pain only when administrated in the maintenance phase. Combined targeting of srGAP3 in the initiation phase and Rac1 in the maintenance phase can produce optimal analgesic efficacy. Abstract Neuropathic pain includes an initiation phase and maintenance phase, each with different pathophysiological processes. Understanding the synaptic plasticity and molecular events in these two phases is relevant to exploring precise treatment strategies for neuropathic pain. In the present study, we show that dendritic spine density increases in the spinal dorsal horn in the initiation phase of neuropathic pain induced by paclitaxel and that the spine maturity ratio increases in the maintenance phase. Increased srGAP3 (slit‐robo GTPase activating protein 3) facilitates dendritic spine sprouting in the initiation phase. In the maintenance phase, srGAP3 decreases to upregulate Rac1 activity, which facilitates actin polymerization and dendritic spine maturation and thus the persistence of neuropathic pain. Knockdown of srGAP3 in the initiation phase or inhibition of Rac1 in the maintenance phase attenuates neuropathic pain. Combined intervention of srGAP3 in the initiation phase, and Rac1 in the maintenance phase shows better analgesic efficacy against neuropathic pain. The present study demonstrates the role of srGAP3‐Rac1 in dendritic spine plasticity in the two phases of neuropathic pain and, accordingly, provides treatment strategies for different phases of neuropathic pain.

BackgroundA totally implantable venous access device (TIVAD) provides reliable, long-term vascular access and improves patients’ quality of life. The wide use of TIVADs is associated with important complications. A meta-analysis was undertaken to compare the internal jugular vein (IJV) with the subclavian vein (SCV) as the percutaneous access site for TIVAD to determine whether IJV has any advantages.MethodsAll randomized controlled trials (RCTs) and cohort studies assessing the two access sites, IJV and SCV, were retrieved from PubMed, Web of Science, Embase, and OVID EMB Reviews from their inception to December 2015. Random-effects models were used in all analyses. The endpoints evaluated included TIVAD-related infections, catheter-related thrombotic complications, and major mechanical complications.ResultsTwelve studies including 3905 patients published between 2008 and 2015, were included. Our meta-analysis showed that incidences of TIVAD-related infections (odds ratio [OR] 0.71, 95 % confidence interval [CI] 0.48–1.04, P = 0.081) and catheter-related thrombotic complications (OR 0.76, 95 % CI 0.38–1.51, P = 0.433) were not significantly different between the two groups. However, compared with SCV, IJV was associated with reduced risks of total major mechanical complications (OR 0.38, 95 % CI 0.24–0.61, P < 0.001). More specifically, catheter dislocation (OR 0.43, 95 % CI 0.22–0.84, P = 0.013) and malfunction (OR 0.42, 95 % CI 0.28–0.62, P < 0.001) were more prevalent in the SCV than in the IJV group; however, the risk of catheter fracture (OR 0.47, 95 % CI 0.21–1.05, P = 0.065) were not significantly different between the two groups. Sensitivity analyses using fixed-effects models showed a decreased risk of catheter fracture in the IJV group.ConclusionThe IJV seems to be a safer alternative to the SCV with lower risks of total major mechanical complications, catheter dislocation, and malfunction. However, a large-scale and well-designed RCT comparing the complications of each access site is warranted before the IJV site can be unequivocally recommended as a first choice for percutaneous implantation of a TIVAD.

It was the first time to prove that oxaliplatin-induced neuropathic pain was correlated to the activation of the CaN/NFAT pathway in our rat model. This finding can provide a new direction for explore the mechanism of oxaliplatin-induced neuropathic pain.

No abstract

No abstract