Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats. CX3CR1 siRNA-treated rats exhibited significant reductions in the activation of microglia in the spinal dorsal horn and a downregulation of proinflammatory mediators, as well as a significant attenuation of mechanical allodynia. These data indicate that the PLGA-encapsulated CX3CR1 siRNA nanoparticles effectively reduce neuropathic pain in SNL-induced rats by reducing microglial activity and the expression of proinflammatory mediators. Therefore, we believe that PLGA-encapsulated CX3CR1 siRNA nanoparticles represent a valuable new treatment option for neuropathic pain.
Background and Objectives: The effect of supra-inguinal fascia iliaca compartment block (SI-FICB) in hip arthroscopy is not apparent. It is also controversial whether SI-FICB can block the obturator nerve, which may affect postoperative analgesia after hip arthroscopy. We compared analgesic effects before and after the implementation of obturator nerve block into SI-FICB for hip arthroscopy. Materials and Methods: We retrospectively reviewed medical records of 90 consecutive patients who underwent hip arthroscopy from January 2017 to August 2019. Since August 2018, the analgesic protocol was changed from SI-FICB to SI-FICB with obturator nerve block. According to the analgesic regimen, patients were categorized as group N (no blockade), group F (SI-FICB only), and group FO (SI-FICB with obturator nerve block). Primary outcome was the cumulative opioid consumption at 24 hours after surgery. Additionally, cumulative opioid consumption at 6 and 12 hours after surgery, pain score, additional analgesic requests, intraoperative opioid consumption and hemodynamic stability, and postoperative nausea and vomiting were assessed. Results: Among 87 patients, there were 47 patients in group N, 21 in group F, and 19 in group FO. The cumulative opioid (fentanyl) consumption at 24 hours after surgery was significantly lower in the group FO compared with the group N (N: 678.5 (444.0–890.0) µg; FO: 482.8 (305.8–635.0) µg; p = 0.014), whereas the group F did not show a significant difference (F: 636.0 (426.8–803.0) µg). Conclusion: Our findings suggest that implementing obturator nerve block into SI-FICB can reduce postoperative opioid consumption in hip arthroscopy.
Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.
In practical quantum key distribution (QKD) systems, the heralded single photon source (HSPS) based on parametric down-conversion (PDC) has attracted significant attentions from many researchers because its various advantages compared to the weak coherent source. We propose a heralded single photon source-based decoy-state QKD with dual detectors and demonstrate in a theoretical simulation that this method improves the performance of QKD system. The secure key generation rate is increased significantly with our proposal both in thermal and Poisson distributions of photons. The secure key rate produced by our scheme is higher than the state of the art key rate of current high-speed QKD system. The decoy-state QKD system using the heralded single photon source with dual detectors can be an important alternative for the present practical QKD systems.
Opioid-sparing effects of nefopam during patient-controlled analgesia (PCA) are well demonstrated. We hypothesized that postoperative pain control with an opioid-equivalent dose of nefopam as a single analgesic agent for PCA would not be inferior to fentanyl in laparoscopic gynecologic surgery. In total, 135 patients were randomly assigned to the N (nefopam 200 mg), NF (fentanyl 500 mcg + nefopam 100 mg), and F (fentanyl 1000 mcg) groups (n = 45 patients per group). The primary outcome was the numerical rating scale (NRS) score at rest at 6 h postoperatively, and the non-inferiority limit was set to 1. Secondary outcomes were pain severity and incidence of nausea and vomiting for 48 h postoperatively. Mean differences (MD) in primary outcome between the N and F groups were 0.4 (95% confidence interval (CI) −0.5 to 1.3). The upper limit of 95% CI exceeded the non-inferiority limit. The N group showed higher pain scores than the NF group (MD, 1.1; 95% CI, 0.3–1.9) in pairwise comparisons. No significant intergroup differences were observed in the cumulative dose of PCA usage and incidence of postoperative nausea and vomiting (PONV). In laparoscopic gynecological surgery, nefopam alone showed limited efficacy for postoperative pain control.
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