A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation.

Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primary somatosensory cortex of hindlimb (S1HL) mediates the disinhibition and subsequent hyperexcitation of glutamatergic neurons in the S1HL (S1HLGlu), which then drives secondary mechanical hypersensitivity development in ipsilateral hindpaws of mice with forepaw amputation. Forepaw amputation induces rapid S1FL microglial activation that further activates S1HL microglia via the CCL2-CCR2 signaling pathway. Increased engulfment of GABAergic presynapses by activated microglia stimulates S1HLGlu neuronal activity, ultimately leading to secondary mechanical hypersensitivity of hindpaws. It is widely believed direct neuronal projection drives interactions between distinct brain regions to prime specific behaviors. Our study reveals microglial interactions spanning different subregions of the somatosensory cortex to drive a maladaptive neuronal response underlying secondary mechanical hypersensitivity at non-injured sites.

Corrigendum: Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

[This corrects the article DOI: 10.3389/fpsyt.2022.889637.].

Application of Continuous Sacral Block Guided by Ultrasound After Comprehensive Sacral Canal Scanning in Children Undergoing Laparoscopic Surgery: A Prospective, Randomized, Double-Blind Study.

Purpose: The present study aimed to explore the effects of continuous sacral block on the postoperative pain of children and the satisfaction of the nurses in post-anesthesia care unit (PACU). Also, the influence of the modified protocol of continuous sacral block was investigated. Patients and Methods: A total of 60 children undergoing laparoscopic surgery were randomly divided into two groups: GI and GC groups. The general anesthesia was induced with midazolam, propofol, sufentanil and succinylcholine in both groups. In addition, the patients were subjected to continuous sacral block with levobupivacaine in group GC. The modified protocol of continuous sacral block was divided into three steps: comprehensive lumbar and sacral vertebral canal scanning by ultrasound, catheterization and administration. The EVENDOL pain scales and pediatric anesthesia emergence delirium scales of the children were evaluated at 5 min after extubation (T3), 90 min (T4), and 4 h (T5) after the operation. The nurses' satisfaction scores at T3 -T4 and adverse events, such as nausea and vomiting, were also recorded, after the operation. Results: After ultrasonic scanning, one patient in group GC was excluded due to the sacral hiatus atresia, which might lead to failure of catheterization. Data of 59 patients were collected for statistical analysis. Compared to the GI group, the EVENDOL scores and the pediatric anesthesia emergence delirium scales were reduced at T3, T4, and T5 (P < 0.05) in group GC. Furthermore, there was a higher rank of PACU nurses' satisfaction in the GC group compared to the GI group (P < 0.05). Conclusion: Based on the modified protocol, continuous sacral block provides reliable and safety analgesia for children undergoing laparoscopic surgery, thereby improving the satisfaction of PACU nurses.

Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

Background: We previously demonstrated that flurbiprofen increased arterial oxygen partial pressure and reduced intrapulmonary shunts. The present study aims to investigate whether flurbiprofen improves intraoperative regional cerebral oxygen saturation (rScO2) and reduces the incidence of postoperative delirium (POD) in elderly patients undergoing one-lung ventilation (OLV). Methods: One hundred and twenty patients undergoing thoracoscopic lobectomy were randomly assigned to the flurbiprofen-treated group (n = 60) and the control-treated group (n = 60). Flurbiprofen was intravenously administered 20 minutes before skin incision. The rScO2 and partial pressure of arterial oxygen (PaO2) were recorded during the surgery, and POD was measured by the Confusion Assessment Method (CAM) within 5 days after surgery. The study was registered in the Chinese Clinical Trial Registry with the number ChiCTR1800020032. Results: Compared with the control group, treatment with flurbiprofen significantly improved the mean value of intraoperative rScO2 as well as the PaO2 value (P < 0.05, both) and significantly reduced the baseline values of the rScO2 area under threshold (AUT) (P < 0.01) at 15, 30, and 60 min after OLV in the flurbiprofen-treated group. After surgery, the POD incidence in the flurbiprofen-treated group was significantly decreased compared with that in the control group (P < 0.05). Conclusion: Treatment with flurbiprofen may improve rScO2 and reduce the incidence of POD in elderly patients undergoing thoracoscopic one-lung ventilation surgery for lung cancer. Clinical trial registration: http://www.chictr.org/cn/, identifier ChiCTR1800020032.

Effect of Perineural Dexamethasone with Ropivacaine in Continuous Serratus Anterior Plane Block for Postoperative Analgesia in Patients Undergoing Video-Assisted Thoracoscopic Surgery.

Purpose: The goal of this study was to evaluate the analgesic efficiency of dexamethasone with ropivacaine in continuous serratus anterior plane block (cSAPB) after video-assisted thoracoscopic surgery (VATS). Patients and Methods: Sixty-six patients who underwent VATS were randomized into two groups. All patients received cSAPB postoperatively, and patients in Group RD received 20 mL of 0.375% ropivacaine plus 0.1 mg/kg dexamethasone followed by an infusion of 0.2% ropivacaine plus 0.02 mg/kg/hour dexamethasone at a rate of 5 mL/h in patient-controlled analgesia (PCA) pump. Patients in Group R received 20 mL of 0.375% ropivacaine with normal saline followed by an infusion of 5 mL/h of 0.2% ropivacaine in PCA pump. Fifty milligrams of tramadol was given as rescue medication when the visual analog scale (VAS) score was ≥4 at rest. The primary outcomes were the sum of pressing number within 48 hours postoperatively and the time to the first patient-controlled bolus. The secondary outcomes were VAS scores, the incidence of rescue analgesia, wound infection and nausea/vomiting. Results: Within 48 hours postoperatively, the sum of pressing number was more in Group R (18.33 ± 3.149 vs 16.09 ± 3.292, P = 0.006), and the Log Rank Test showed a significant difference in time to the first patient-controlled bolus (P = 0.006). After the PCA infusion finished, there were significantly lower VAS scores in Group RD at 60 and 72 hours postoperatively (P < 0.001). Additionally, the incidence of rescue analgesia in Group R was significantly more than that in Group RD (P < 0.001). No incision infection was observed in any patient. Conclusion: The cSAPB with ropivacaine plus dexamethasone prolonged the duration of analgesia and motor blockade, reduced pain intensity and rescued analgesia requirements after the end of PCA infusion for patients undergoing VATS, which provide further improvement to continuous perineural block.

Retraction Notice to: FABP4 facilitates inflammasome activation to induce the Treg/Th17 imbalance in preeclampsia via forming a positive feedback with IL-17A.

[This retracts the article DOI: 10.1016/j.omtn.2021.03.020.].

Continuous Serratus Anterior Plane Block Improved Early Pulmonary Function After Lung Cancer Surgical Procedure.

BACKGROUND: Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS: From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded. RESULTS: A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P < .001), but lung function variables in the continuous SAPB group were significantly higher (P < .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P < .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P < .05). CONCLUSIONS: Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

The Role of Serratus Anterior Plane Block During in Video-Assisted Thoracoscopic Surgery.

Although thoracoscopy has characteristics such as a small surgical incision and low stress response, post-surgical pain after a thoracoscopic operation is no less than that after a thoracotomy. Moreover, poor post-surgical pain management is likely to cause an increased incidence of postoperative pulmonary complications (PPCs) and chronic post-surgical pain. The serratus anterior plane block (SAPB) is a regional anesthesia method whereby local anesthetics (LAs) are injected into the serratus anterior space to block the lateral cutaneous branch of the intercostal nerve, long thoracic nerve, and dorsal thoracic nerve. The block range of the SAPB covers the incisions of video-assisted thoracoscopic surgery (VATS) and the site of the chest tube, which are often located in the antero-lateral chest wall. Therefore, the SAPB can achieve effective analgesia in VATS. For example, 0.125% to 0.25% levobupivacaine (20-25 ml) is widely used for thoracic surgery, which can achieve effective analgesia and avoid adverse reactions. Moreover, it has advantages compared with thoracic segmental epidural block (TEA) and thoracic paravertebral block (TPVB), such as simple operation, increased safety, fewer complications, and hemodynamic stability. In addition, adequate analgesia is helpful for pulmonary function recovery and reduces the incidence of PPCs. This article introduces the anatomical mechanism of the SAPB, diverse operation approaches, how to choose drugs and adjuvants, and the resulting impacted area range. It summarizes the advantages and disadvantages of the SAPB compared with other analgesic methods and posits that the SAPB is beneficial to the recovery of postoperative lung function, which provides more options for postoperative analgesia after VATS.

FABP4 facilitates inflammasome activation to induce the Treg/Th17 imbalance in preeclampsia via forming a positive feedback with IL-17A.

Preeclampsia (PE) is one of the leading causes of maternal death worldwide. Elevated fatty acid binding protein 4 (FABP4) levels have been observed in patients with PE, however, the mechanism by which FABP4 contributes to the pathogenesis of PE remains unclear. In this study, we compared the levels of FABP4 and cytokines between 20 PE patients and 10 healthy pregnant women by using ELISA, immunohistochemistry (IHC) analysis, and flow cytometry (fluorescence-activated cell sorting, FACS). Elevated FABP4 was accompanied by regulatory T (Treg)/T helper type 17 (Th17) imbalance in PE. Knockdown of FABP4 attenuated lipopolysaccharide (LPS)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-17A (IL-17A) production in primary macrophages. In addition, silencing of FABP4 also suppressed Th17 differentiation via paracrine signaling. Overexpression of FABP4 promoted Th17 differentiation via increasing IL-17A/IL-23 release. Reciprocally, IL-17A upregulated FABP4 and activated the NLRP3 inflammasome in vitro and in vivo. The in vivo studies revealed that FABP4 inhibitor BMS309403 ameliorated PE clinical phenotypes, the Treg/Th17 imbalance, and NLRP3 inflammasome activation in PE mice model. In conclusion, FABP4 facilitates inflammasome activation to induce the imbalance of Treg/Th17 in PE via forming a positive feedback with IL-17A.

Operation, Effectiveness, and Limitations of Continuous Serratus Anterior Plane Blocks for Thoracoscopic Surgery in Adults.

PURPOSE: This randomized, double-blind study evaluated the effectiveness and limitations of continuous serratus anterior plane block (cSAPB) by comparing the effect of cSAPB to patient-controlled intravenous analgesia (PCIA) on postoperative acute pain after thoracoscopic surgery in adults. PATIENTS AND METHODS: Sixty-six patients who underwent elective video-assisted thoracoscopic surgery (VATS) were randomly allocated to cSAPB or PCIA groups (n=33 per group) after surgery. For the cSAPB group, patients were treated by an initial does of 20 mL ropivacaine (0.375%), followed by continuous infusion at a rate of 5 mL/h of ropivacaine (0.2%) and a patient-controlled bolus of 5 mL ropivacaine (0.2%). PCIA started with an initial does of 0.03 µg/kg sufentanil, followed by a basal infusion of 0.03 µg/kg/h sufentanil and a patient-controlled bolus of 0.03 µg/kg sufentanil. Visual analog scale (VAS) and other items were examined postoperatively. The area under the curve of VAS-time (AUCVAS-time) at rest and on coughing in the first 24 hours postoperatively were primary outcomes. RESULTS: At the first 24 hours postoperatively, patients in the cSAPB group exhibited a smaller AUCVAS-time at rest (44.0±17.1 vs 68.9±11.8 cm·h, P<0.001) and AUCVAS-time on coughing (67.1±8.8 vs 78.0±12.5 cm·h, P<0.001) compared with those in the PCIA group. The differences in means of VAS score at rest were more than 1.0 cm between the two groups, however, on coughing they were less than 1.0 cm at each observation point. Additionally, patients in the cSAPB group had a longer time to first patient-controlled bolus (15.8±7.6 vs 10.6±8.6 hours, P=0.011). Furthermore, a higher rank of satisfaction was recorded with patients in the cSAPB group. CONCLUSION: cSAPB using PCA devices might be superior to traditional intravenous continuous analgesia, particularly with an advantage of pain relief at rest following VATS operation. Meanwhile, cSAPB lacks a satisfactory analgesic effect on cough.

A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery.

The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-ß levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients.