Effect of pericapsular nerve group block and suprainguinal fascia iliaca block on postoperative analgesia and stress response in elderly patients undergoing hip arthroplasty: a prospective randomized controlled double-blind trial.

BACKGROUND: As a novel regional analgesic technique, ultrasound-guided pericapsular nerve group (PENG) block has some potential advantages, and we designed a randomized clinical trial (RCT) to investigate whether the ultrasound-guided PENG block combined with general anesthesia can better reduce stress response, maintain intraoperative hemodynamic stability, and reduce postoperative analgesia in elderly hip arthroplasty compared with ultrasound-guided suprainguinal fascia iliaca block (SIFIB) combined with general anesthesia. METHODS: Seventy-four subjects were enrolled over an 8-month period (20 April 2023 to 31 December 2023). All patients were divided into the test group (group P) and the control group (group S) using the envelope as the randomization method. The test group was treated with preoperative ultrasound-guided PENG block analgesia combined with general anesthesia and the control group was treated with preoperative ultrasound-guided SIFIB analgesia combined with general anesthesia. The primary outcome selected was the patient Visual Analogue Scale (VAS) score at 12 h postoperatively. RESULTS: After generalized estimating equations (GEE) analysis, there was a statistically significant difference in the main effect of postoperative VAS score in group P compared with group S (P = 0.009), the time effect of VAS score in each group was significantly different (P < 0.001), and there was no statistically significant difference in the group-time interaction effect (P = 0.069). There was no statistically significant difference in the main effect of intraoperative mean arterial pressure (MAP) change (P = 0.911), there were statistically significant differences in the time effect of MAP in each group (P < 0.001), and there were statistically significant differences in the interaction effect (P < 0.001). CONCLUSIONS: In summary, we can conclude that in elderly patients undergoing hip fracture surgery, postoperative analgesia is more pronounced, intraoperative hemodynamic parameters are more stable, and intraoperative stress is less induced in patients receiving SIFIB than in patients receiving PENG block.

The Effect of Depth of Anesthesia on Postoperative Pain in Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.

BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.

Engineering Relaxation-Paths of C-Exciton for Constructing Band Nesting Bypass in WS2 Monolayer.

Transition-metal dichalcogenides exhibit strong photon absorption characteristics in the band nesting region (denoted as C-exciton) due to intrinsic van Hove singularities despite being atomically thin. However, because of unique parallel band structure and ineluctably unfavorable recombination process, only a small fraction of the hot carriers from C-excitons are converted into optically active band-edge excitons via inherent relaxation-paths. The resultant photoluminescence quantum yield (PLQY) is severely suppressed for the resonant excitation of C-exciton. To overcome this limitation, we have designed double type-I band alignments to construct a band nesting bypass in a monolayer WS2/CdS quantum dot heterostructure for cooling the C-excitons. Transient optical measurements confirmed that the hot carriers from the C-excitons were effectively transferred from WS2 to CdS with an efficiency of 50% and subsequently back to the WS2 band-edge to form A-excitons over an ultrafast subpicosecond time scale, accompanied by a record high PLQY of ∼11.1% for near-resonance C-exciton excitation.

Directed exfoliating and ordered stacking of transition-metal-dichalcogenides.

Two-dimensional van der Waals crystals provide a limitless scope for designing novel combinations of physical properties by controlling the stacking order or twist angle of individual layers. Lattice orientation between stacked monolayers is significant not only for breaking the engineering symmetry but also for the study of many-body quantum phases and band topology. Thus far the state-of-the-art exfoliation approaches focus on the achievements of quality, size, yield, and scalability, while lacking sufficient information on lattice orientation. Consequently, interlayer alignment is usually determined by later experiments, such as the second harmonic generation spectroscopy, which increase the number of trials and errors for a designed artificial ordering and hampered the efficiency of systematic study. Herein, we report a lattice orientation distinguishable exfoliation method via gold favor epitaxy along the specific atomic step edges, meanwhile, fulfilling the requirements of high-quality, large-size, and high-yield monolayers. Hexagonal- and rhombohedral-stacking configurations of bilayer transition metal dichalcogenides are built directly at once as a result of foreseeing the lattice orientation. Optical spectroscopy, electron diffraction, and angle-resolved photoemission spectroscopy are used to study crystal quality, symmetric breaking, and band tuning, which support the exfoliating mechanism we proposed. This strategy shows the ability to facilitate the development of ordering stacking especially for multilayers assembling in the future.

Corrigendum: Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance.

[This corrects the article DOI: 10.3389/fpsyt.2021.679206.].

Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance.

Heroin use disorder is a chronic and relapsing disease that induces persistent changes in the brain. The diagnoses of heroin use disorders are mainly based on subjective reports and no valid biomarkers available. Recent researches have revealed that circulating miRNAs are useful non-invasive biomarkers for diagnosing brain diseases such as Alzheimer's disease, multiple sclerosis, schizophrenia, and bipolar disorder. However, studies on circulating miRNAs for the diagnosis of heroin use disorders are rarely reported. In this study, we investigated the differential expression of plasma miRNAs in 57 heroin-dependent patients. Based on literature research and microarray analysis, two candidate miRNAs, miR-320a and let-7b-5p, were selected and analyzed by quantitative real-time RT-PCR. The results showed miR-320a and let-7b were significantly upregulated in plasma of the heroin-dependent patients compared to that in healthy controls. The area under curves (AUCs) of receiver operating characteristic (ROC) curves of miR-320a and let-7b-5p were 0.748 and 0.758, respectively. The sensitivities of miR-320a and let-7b-5p were 71.9 and 70.2%, while the specificities of miR-320a and let-7b-5p were 76.1 and 78.3%, respectively. The combination of these two miRNAs predicted heron dependence with an AUC of 0.782 (95% CI 0.687-0.876), with 73.7% sensitivity and 82.6% specificity. Our findings suggest a potential use for circulating miRNAs as biomarkers for the diagnosis of heroin abuse.

Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway.

Colorectal cancer (CRC) is responsible for thousands of slow and painful annual deaths. Propofol, an anesthetic, is commonly used in CRC surgery. The role of circularRNA0026344 (circ_0026344) in propofol-treated CRC remains unclear, which was further explored in this study. Real-time polymerase chain reaction (qPCR) was used to detect the expression of circ_0026344 and microRNA645 (miR-645) in CRC cells and normal cells. Western blot was devoted to testing the protein expression of phospho-protein kinase B (p-AKT), AKT, phospho-mammalian target of rapamycin (p-mTOR), and mTOR in CRC cells. Moreover, cell counting kit-8 (CCK8), colony formation, flow cytometry, and transwell assays were employed to assess the proliferation, apoptosis, and metastasis in CRC cells. Circinteractome online tool was applied to predict the combination between circ_0026344 and miR-645, which was further verified by dual-luciferase reporter system. circ_0026344 was lowly expressed and miR-645 was abundantly expressed in CRC cells. The relative protein expression of p-AKT/AKT and p-mTOR/mTOR was strikingly elevated by si-circ#1, which could be reversed by anti-miR-645 in propofol-treated CRC cells. circ_0026344 overexpression inhibited the proliferation and metastasis and promoted apoptosis in CRC cells. Propofol treatment induced the restraint in proliferation and metastasis and stimulation in apoptosis, which were allayed by si-circ#1; meanwhile, this alleviation could further be abolished by anti-miR-645 in CRC cells. Furthermore, circ_0026344 sponged miR-645 to inhibited Akt/mTOR signal pathway in propofol-treated CRC cells. Propofol postponed CRC process by circ_0026344/miR-645/Akt/mTOR axis. This finding might provide a possibility to improve the therapy of CRC with propofol.

Higher uric acid is associated with better discharge recovery and short-term outcome in stroke patients treated with thrombolysis.

BACKGROUND: Uric acid (UA) possesses antioxidant features and potential neuroprotective effects. However, conflicting results regarding the association between serum uric acid (SUA) levels and the prognosis of stroke have been obtained. We aimed to assess whether SUA is related to discharge recovery and short-term outcomes in patients who underwent thrombolysis therapy. METHODS: We recruited 393 consecutive patients who were diagnosed with acute ischaemic stroke (AIS) and treated with thrombolysis. The demographic information, including sex and age, was collected. Haematology tests, including SUA, fasting plasma glucose (FPG), and blood lipid parameters, were performed under fasting conditions the morning after admission. The modified Rankin Scale (mRS) was used to assess the functional outcome of patients at discharge and 3 months after onset. RESULTS: A negative correlation was observed between the levels of SUA and the National Institute of Health Stroke Scale (NIHSS) score at discharge (r = - 0.171, P = 0.003). Additionally, a positive correlation was observed between the levels of SUA and the difference between the baseline NIHSS and discharge NIHSS (r = 0.118, P = 0.032). The levels of SUA in the patients with good outcomes (353.76 ± 93.05) were higher than those in the patients with poor outcomes (301.99 ± 92.24; P = 0.015) at 3 months. The multivariate logistic regression analysis demonstrated that a higher SUA level (odds ratio 0.988, 95% confidence interval 0.985-0.991, P = 0.002) was an independent predictor of a good outcome at 3 months. CONCLUSION: Higher SUA levels were associated with better discharge recovery and 3-month outcomes in patients with ischaemic stroke who received thrombolysis.

Ultrasound-guided transversus abdominis plane block using ropivacaine and dexmedetomidine in patients undergoing caesarian sections to relieve post-operative analgesia: A randomized controlled clinical trial.

Dexmedetomidine, which is a highly selective α2 adrenoreceptor agonist, enhances the analgesic efficacy and prolongs the analgesic duration when administered in combination with local anesthetics. The current study aimed to evaluate the effects of dexmedetomidine combined with ropivacaine in ultrasound-guided transversus abdominis plane (TAP) block on post-operative analgesia following cesarean section (CS). A total of 70 patients scheduled for CS were divided randomly into 2 groups: The ropivacaine (R) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml 0.9% normal saline, and the dexmedetomidine (RD) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml dexmedetomidine (0.5 µg/kg). The primary outcome was pain-free duration, and secondary outcomes included heart rate (HR) and mean blood pressure (MBP) measurements, visual analogue scale (VAS) pain scores, number of patients who required rescue analgesic, time to first request for analgesia and patient satisfaction. There was no significant difference in HR and MBP between the two groups at 1 h post-surgery (P>0.05). However, VAS pain scores decreased at 6 and 8 h post-surgery [2 (1-2) vs. 0 (0-0.25) and 2 (2-3) vs. 0 (0-1), respectively; P<0.05], pain-free duration was prolonged (5.91±1.08 vs. 9.62±1.46 h; P<0.05), the number of patients who required rescue analgesic was reduced (19 vs. 9; P<0.05), the time to first request for analgesia was prolonged (7.10±1.21 vs. 11.60±2.11 h; P<0.05) and patient satisfaction was improved [3.5 (3-4) vs. 4 (4-5); P<0.05] in the RD group compared with the R group. Furthermore, no bradycardia or hypotension was observed. In conclusion, the results of the present study demonstrated that adding 0.5 µg/kg dexmedetomidine to 0.3% ropivacaine used in TAP block in patients undergoing CS prolonged pain-free duration, decreased VAS pain scores, reduced the number of patients who required rescue analgesic, prolonged the time to first request for analgesia and improved the patient satisfaction without serious side effects.

Increased expression of plasma hsa-miR-181a in male patients with heroin addiction use disorder.

BACKGROUND: Drug addiction is an uncontrolled, chronic, and recurrent encephalopathy that presently lacks specific and characteristic biomarkers for diagnosis and treatment. As regulators of gene expression, microRNAs (miRNAs) are increasingly used for diagnostic and prognostic purposes in various disease states. Previous studies indicated that miRNAs play important roles in the development and progression of drug addictions, including addiction to methamphetamine, cocaine, alcohol, and heroin. METHODS: We identified significant miRNAs using the microarray method and then validated the hsa-miR-181a expression levels in 53 heroin addiction patients and 49 normal controls using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the potential associations between transcriptional levels in heroin addiction patients and their clinicopathological features were analyzed. RESULTS: A total of 2006 miRNAs were differentially expressed between heroin addiction patients and normal controls. The top 10 up-regulated miRNAs in patients were hsa-miR-21a, hsa-miR-181a, hsa-miR-4459, hsa-miR-4430, hsa-miR-4306, hsa-miR-22-3P, hsa-miR-486-5P, hsa-miR-371b-5P, hsa-miR-92a-3P, and hsa-miR-5001-5P. The top 10 down-regulated miRNAs in patients were hsa-miR-3195, hsa-miR-4767, hsa-miR-3135b, hsa-miR-6087, hsa-miR-1181, hsa-miR-4785, hsa-miR-718, hsa-miR-3141, hsa-miR-652-5P, and hsa-miR-6126. The expression level of hsa-miR-181a in heroin addiction patients was significantly increased compared with that in normal controls (P < .001). The area under the receiver operating characteristic curve of hsa-miR-181a was 0.783, the sensitivity was 0.867, and the specificity was 0.551. CONCLUSIONS: The increased expression of hsa-miR-181a in the plasma of heroin patients may be a consequence of the pathological process of heroin abuse. This study highlights the potential of hsa-miR-181a as a novel biomarker for the diagnosis of heroin addiction.

Transesophageal Echocardiographic Measurements of the Superior Vena Cava for Predicting Fluid Responsiveness in Patients Undergoing Invasive Positive Pressure Ventilation.

OBJECTIVES: Preoperative fasting, water deprivation, and intraoperative fluid loss and redistribution result in hypovolemia in patients undergoing surgery. Some findings have indicated that the superior vena cava (SVC) diameter and variation, as determined by transesophageal echocardiography during surgery, do not reflect central venous pressure effectively. This study aimed to compare and correlate the SVC diameter and variation with the stroke volume variation for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation. METHODS: Thirty-six patients scheduled for elective gastrointestinal surgery under general anesthesia with invasive positive pressure ventilation were included in this study. After anesthesia induction, the stroke volume variation, SVC diameter, mean arterial pressure, central venous pressure, and pulse were recorded, and measurements after fluid challenge were recorded as well. The SVC variation was calculated before and after the fluid challenge. RESULTS: After the fluid challenge, the SVC diameter markedly increased, whereas the SVC variation and stroke volume variation significantly decreased (P < .05). The optimal cutoff value for the SVC variation was 21.1%, and the area under the curve (AUC) from a receiver operating characteristic curve analysis was 0.849. The optimal cutoff value for the minimal SVC diameter was 1.135 cm, and that AUC was 0.929. In addition, the optimal cutoff value for the maximal SVC diameter was 1.480 cm, and the AUC was 0.862. CONCLUSIONS: The minimal SVC diameter may be an effective indicator for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation.

Strawberry Vein Banding Virus P6 Protein Is a Translation Trans-Activator and Its Activity Can be Suppressed by FveIF3g.

The strawberry vein banding virus (SVBV) open reading frame (ORF) VI encodes a P6 protein known as the RNA silencing suppressor. This protein is known to form inclusion like granules of various sizes and accumulate in both the nuclei and the cytoplasm of SVBV-infected plant cells. In this study, we have determined that the P6 protein is the only trans-activator (TAV) encoded by SVBV, and can efficiently trans-activate the translation of downstream gfp mRNA in a bicistron derived from the SVBV. Furthermore, the P6 protein can trans-activate the expression of different bicistrons expressed by different caulimovirus promoters. The P6 protein encoded by SVBV from an infectious clone can also trans-activate the expression of bicistron. Through protein-protein interaction assays, we determined that the P6 protein could interact with the cell translation initiation factor FveIF3g of Fragaria vesca and co-localize with it in the nuclei of Nicotiana benthamiana cells. This interaction reduced the formation of P6 granules in cells and its trans-activation activity on translation.

Effect of dexmedetomidine added to ropivicaine for caudal anesthesia in patients undergoing hemorrhoidectomy: A prospective randomized controlled trial.

BACKGROUND: To assess the effect of dexmedetomidine added to ropivaccaine on the onset and duration of sensory block, as well as postoperative analgesia during caudal anesthesia in patients undergoing hemorrhoidectomy. METHODS: Fifty adult patients scheduled for hemorrhoidectomy were divided into 2 groups. The group R received caudal anesthesia using 18 mL 0.3% ropivacaine plus 2 mL normal saline. The group RD received 18 mL 0.3% ropivacaine plus 2 mL 1 µg/kg dexmedetomidine. Heart rate, mean blood pressure, onset time and duration of sensory block, and duration of analgesia were observed. RESULTS: The onset time of sensory block was shortened (9.2 ±â€Š1.3 vs 7.2 ±â€Š1.2), and the duration of sensory block (3.0 ±â€Š0.7 vs 3.8 ±â€Š0.8) and duration of analgesia (3.9 ±â€Š0.7 vs 5.3 ±â€Š0.8) were prolonged in group RD compared with group R (P < .05). The heart rate and the mean blood pressure were also lower in the group RD compared with group R at each observation time points, except the baseline (P < .05). No bradycardia or hypotension was reported. CONCLUSION: Dexmedetomidine as an adjuvant to ropivacaine prolonged the duration of caudal block and improved postoperative analgesia without significant side effects in adult patients undergoing hemorrhoidectomy.

Dexmedetomidine inhibits inflammatory reaction in the hippocampus of septic rats by suppressing NF-κB pathway.

Dexmedetomidine (DEX) is known to provide neuroprotective effect in the central nervous system. However, the detailed mechanism remains far more elusive. This study was designed to investigate the relevant mechanisms of DEX's neuroprotective effect. Sprague-Dawley (SD) rats were injected with dexmedetomidine and/or Lipopolysaccharide (LPS) intraperitoneally, and inflammatory cytokines in serum and in the hippocampus were measured by enzyme linked immunosorbent assay (ELISA). NF-κB in the brain tissue extracts was analyzed with western-blot. Then, we investigated whether NF-κB inhibitor prevents the elevation of inflammatory cytokines in rats injected with LPS. Our results indicated that compared with the control group, the rats exposed to LPS showed significant cognitive dysfunction. When compared to controls, the levels of TNF-α and IL-6 in the serum and hippocampus homogenate were increased in rats treated with LPS. DEX pretreatment inhibited the rats' TNF-α, IL-6 and NF-κB levels induced by LPS. In response to LPS, PDTC pretreatment restrains the production of proinflammatory cytokines (TNF-α and IL-6). Rats treated with PDTC and DEX alongside LPS exhibited less TNF-α and IL-6 than the LPS treated group. In combination, PDTC and DEX showed addictive effects. Our data suggest that DEX exerts a neuroprotective effect through NF-κB in part after LPS-induced cognitive dysfunction.

Further Standardization in the Aneurysm Clip: The Effects of Occlusal Depth on the Outcome of Spinal Cord Injury in Rats.

STUDY DESIGN: Experimental study. OBJECTIVE: To evaluate the relationship between clip occlusal depth and functional and histological outcome measures in a rat model of thoracic spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Aneurysm clip compression is a proven model of contusion-compression SCI, but the relationship between clip depth and outcomes in thoracic SCI is unknown. METHODS: A single aneurysm clip was applied to the spinal cord at thoracic vertebra 10 for 1 minute with an occlusal depth of 2, 6, or 10 mm. The actual compression force was measured using a self-made pulling method. Locomotor function was assessed for 28 days using Basso, Beattie, and Bresnahan (BBB) and inclined plane test (IPT) scores. We then used hematoxylin-eosin and Luxol fast blue staining to histologically quantify cavitation formation, preserved white matter, and preserved grey matter. RESULTS: Greater occlusal compression depths caused greater actual compression forces and worsened functional and histological recovery. The 2- and 10-mm clip injury groups had significantly different BBB and ITP scores; cavitation, preserved white matter, and preserved grey matter volumes; and actual force measures (P < 0.05). CONCLUSION: Our findings show that the occlusal depth of clip compression correlates with actual compression force and recovery impairment. LEVEL OF EVIDENCE: 1.

Triggering Receptor Expressed on Myeloid Cells 2 Overexpression Inhibits Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Microglia.

Microglia play an important role in mediating inflammatory processes in the central nervous system (CNS). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor and could decrease neuropathology in Alzheimer's disease (AD). However, the detailed mechanism remains unclear. This study was designed to elucidate the effect of TREM2 on microglia. We showed that lipopolysaccharide (LPS) stimulation significantly increases proinflammatory cytokines and suppressed TREM2 in microglia. In addition, TREM2 overexpression inhibited LPS-induced microglia activation and elevated M2 phenotype of microglia. Together, our results demonstrate that TREM2 overexpression reduced LPS-induced proinflammatory cytokine release in microglia and increased M2 phenotype of microglia. These findings provide novel insights that the regulation of microglia polarization may be an approach for ameliorating microglia inflammation in neurodegenerative diseases.

Effect of dexmedetomidine as an adjuvant to ropivacaine for wound infiltration in patients undergoing open gastrectomy: A prospective randomized controlled trial.

OBJECTIVES: The primary objective of this study was to investigate whether dexmedetomidine could potentiate the analgesic efficacy of ropivacaine, when added to ropivacaine for wound infiltration in patients undergoing open gastrectomy. METHODS: Fifty patients scheduled for open gastrectomy were divided into 2 equal groups that were received wound infiltration using 20 mL 0.3% ropivacaine plus 2 mL normal saline (group R) or 20 mL 0.3% ropivacaine plus 2 mL 1.0 µg/kg dexmedetomidine (group DR). Visual analogue scale (VAS) pain score, patient-controlled analgesia (PCA) pump press number, sufentanil consumption, postoperative nausea and vomiting (PONV), and wound healing score were recorded. RESULTS: The VAS pain score were comparable between the 2 groups at the observation time points (P > .05), PCA pump press number and sufentanil consumption were higher in group R than that in group DR at 0 to 2, 2 to 4, 4 to 6 time intervals (P < .05) except for 6 to 8, 8 to 10, 10 to 12 time intervals (P > .05), meanwhile, the 24 hours total sufentanil consumption was also higher in group R than that in group DR (90.4 ±â€Š20.5 vs 79.2 ±â€Š9.4) (P < .05), there were no significant differences in PONV and wound healing score between the 2 groups (P > .05). CONCLUSIONS: Dexmedetomidine as an adjuvant to ropivacaine for wound infiltration promoted the analgesic efficacy of ropivacaine, reduced sufentanil consumption, and had no effect on wound healing; it could be as an ideal adjuvant which could potentiate the analgesic efficacy of local anesthetics.

The effects of dexmedetomidine pretreatment on the pro- and anti-inflammation systems after spinal cord injury in rats.

Excessive inflammatory responses play important roles in the aggravation of secondary damage to an injured spinal cord. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, has recently been implied to be neuroprotective in clinical anesthesia, but the underlying mechanism is elusive. As signaling through Toll-like receptor 4 (TLR4) and nicotinic receptors (nAChRs, notably α7nAChR) play important roles in the pro- and anti-inflammation systems in the central nervous system, respectively, this study investigated whether and how they were modulated by DEX pretreatment in a rat model of spinal cord compression. The model was used to mimic perioperative compressive spinal cord injury (SCI) during spinal correction. DEX preconditioning improved locomotor scores after SCI, which was accompanied by increased α7nAChR and acetylcholine (Ach, an endogenous ligand of α7nAChR) expression as well as PI3K/Akt activation. However, there was a decrease in Ly6h (a negative regulator for α7nAChR trafficking), TLR4, PU.1 (a critical transcriptional regulator of TLR4), HMGB1 (an endogenous ligand of TLR4), and caspase 3-positive cells, which was prevented by intrathecal preconditioning with antagonists of either α2R, α7nAChR or PI3K/Akt. In addition, application of an α7nAChR agonist produced effects similar to those of DEX after SCI, while application of an α7nAChR antagonist reversed these effects. Furthermore, both α7nAChR and TLR4 were mainly co-expressed in NeuN-positive cells of the spinal ventral horn, but not in microglia or astrocytes after SCI. These findings imply that the α2R/PI3K/Akt/Ly6h and α7nAChR/PI3K/Akt/PU.1 cascades are required for upregulated α7nAChR and downregulated TLR4 expression by DEX pretreatment, respectively, which provided a unique insight into understanding DEX-mediated neuroprotection.

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia.

Clinically, preoperative anxiety adversely affected postoperative hyperalgesia. As stress-induced glucocorticoids (GCs) were reported to sensitize the activation of microglia, the present study investigated whether and how GCs and microglia played in the process of preoperative anxiety-induced postoperative hyperalgesia. The study used an animal model that exposed rats to single prolonged stress (SPS) procedure to induce preoperative anxiety-like behaviors 24 h before the plantar incisional surgery. Behavioral testing revealed that preoperative SPS enhanced the mechanical allodynia induced by plantar incision. SPS was also found to induce elevated circulating corticosterone levels, potentiate the activation of spinal microglia, and increase the expression of spinal proinflammatory cytokines. Inhibition of microglia by pretreatment with minocycline attenuated the SPS-enhanced mechanical allodynia, and this was accompanied by decreased activation of spinal microglia and expression of proinflammatory cytokines. Another experiment was conducted by administering RU486, the GC receptor (GR) antagonist, to rats. The results showed that RU486 suppressed SPS-induced and SPS-potentiated proinflammatory activation of spinal microglia and revealed analgesic effects. Together, these data indicated that inhibition of stress-induced GR activation attenuated the preoperative anxiety-induced exacerbation of postoperative pain, and the suppression of spinal microglia activation may underlie this anti-hyperalgesia effect. Pending further studies, these findings suggested that GR and spinal microglia may play important roles in the development of preoperative anxiety-induced postoperative hyperalgesia and may serve as novel targets to prevent this phenomenon.

Effect of Repetitive Intracutaneous Injections with Local Anesthetics and Steroids for Acute Thoracic Herpes Zoster and Incidence of Postherpetic Neuralgia.

BACKGROUND: Treatment of established postherpetic neuralgia (PHN) is difficult and often disappointing. In this study, we assessed the efficacy of repetitive intracutaneous injections with local anesthetics and steroids in acute thoracic herpes zoster (HZ) pain, herpetic eruption, and incidence of PHN. METHODS: Ninety-three patients with acute thoracic HZ were randomly assigned to receive a standard treatment of antiviral medication with p.o. analgesics or the standard treatment with the addition of repetitive intracutaneous injections of a local anesthetic and steroid mixture. Patients were permitted to take tramadol when the visual analog scale (VAS) ≥ 4. Pain assessment using VAS was conducted at the initial visit, as well as 1, 2, 4, 12, and 24 weeks after the end of the treatments. RESULTS: In comparison with the standard treatment group, the VAS scores of the intracutaneous injection group were significantly lower during the study. The intracutaneous injection group also reported shorter duration of pain and skin eruption than the control group ( P = 0.005 vs P < 0.001, respectively). At 1 month post-therapy, 12.8% patients in the intracutaneous injection group reported zoster-associated pain, compared with 47.8% in the standard treatment group ( P < 0.001). At 3 and 6 months post-therapy, the incidence of PHN was still significantly lower in the intracutaneous injection group than the standard treatment group. EuroQol VAS scores were significantly higher in the intracutaneous injection group vs standard treatment group (P < 0.001). CONCLUSION: Repetitive intracutaneous injections with local anesthetics and steroids along with standard treatment significantly reduce the duration of pain and herpetic eruption and incidence of PHN.