Electroacupuncture attenuates neuropathic pain via suppressing BIP-IRE-1α-mediated endoplasmic reticulum stress in the anterior cingulate cortex.

Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.

Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats.

Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury (CCI) in the rat spinal dorsal horn. Meanwhile, cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling was also activated with hyperalgesia. Silencing TAOK2 reversed hyperalgesia and suppressed the activation of cGAS-STING signaling induced by CCI, while pharmacological activation of TAOK2 induced pain hypersensitivity and upregulation of cGAS-STING signaling in naive rats. Furthermore, pharmacological inhibition or gene silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia. Taken together, these data demonstrate that the activation of spinal TAOK2 contributes to CCI-induced hyperalgesia via cGAS-STING signaling activation, providing new molecular targets for the treatment of neuropathic pain.

Thoracic endovascular aortic repair of an anastomosis pseudoaneurysm after the Bentall procedure assisted by rapid ventricular pacing: A case report.

Background: Although commonly used for the treatment of descending aortic dissection, endovascular repair is challenging for ascending aortic pseudoaneurysms. Rapid ventricular pacing (RVP), a method that temporarily impedes cardiac output by stopping ventricular activity, heralds potential benefits for thoracic endovascular aortic repair (TEVAR) during precision landing. Recently, we successfully treated an anastomosis pseudoaneurysm after the Bentall procedure using TEVAR assisted by RVP. Case report: A 69-year-old male was admitted to our hospital with a ascending aortic anastomosis pseudoaneurysm. He had undergone a Bentall procedure and a coronary artery bypass grafting nine years prior. After extensive consultation, the decision was made to perform TEVAR with the assistance of RVP. After a covered stent graft was delivered to the precise location of the ascending aorta, RVP was performed at a frequency of 180 beats/min with a pacemaker. When a flattened arterial blood wave of <50 mmHg was observed, the stent graft was released precisely between the opening of the coronary graft and innominate artery. Angiography revealed the presence of an endoleak; therefore, a set of interlock coils were packed into the aneurysm. Subsequent angiography showed intact blood flow in the aorta, superior arch branches, and coronary graft vessels. The patient recovered uneventfully after the procedure. He was discharged six days later and was doing well at the eight-month follow-up. Conclusion: The case indicates that TEVAR assisted by RVP is a promising combination for ascending aortic pseudoaneurysm in selected patients.

The efficacy and safety of remifentanil patient-controlled versus epidural analgesia in labor: A meta-analysis and systematic review.

BACKGROUND: Remifentanil patient-controlled analgesia (rPCA) and epidural analgesia (EA) has been used for pain relief in labor. We aimed to evaluate the efficacy and safety of rPCA versus EA in labor, to provide evidence support for clinical analgesia and pain care. METHODS: We searched PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu databases for RCTs comparing rPCA and EA in labor until February 15, 2022. Two researchers independently screened literature and extracted data. RevMan 5.3 software was used for data analysis. RESULTS: A total of 10 RCTs involving 3086 parturients were enrolled, 1549 parturients received rPCA and 1537 received EA. Meta-analysis indicated that the incidence of intrapartum maternal fever within 1 hour of labor analgesia (OR = 0.43, 95%CI: 0.30~0.62), after 1 hour of labor analgesia (OR = 0.42, 95%CI: 0.20~0.90) in the rPCA was significantly less than that of EA (all P<0.05). The incidence of respiratory depression (OR = 3.56, 95%CI: 2.45~5.16, P<0.001) in the rPCA was significantly higher than that of EA. There were no significant differences in the incidence of Apgar scores<7 at 5 minutes (OR = 1.18, 95%CI: 0.71~1.96, P = 0.53), the patients' satisfaction of pain relief during labor analgesia (SMD = 0.03, 95%CI: -0.40~0.46, P = 0.90) between rPCA and EA (all P>0.05). CONCLUSION: rPCA can be an optional alternative to EA with similar pain relief and less risk of intrapartum maternal fever. However, rPCA was associated with increased risk of respiratory depression. Future studies with rigorous design and larger sample size are needed to provide more reliable evidences for clinical rPCA and EA use.

PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B.

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.

Anesthesia management of combined sequential heart-liver transplantation using a caval clamp without venovenous bypass: A case report.

Familial amyloid polyneuropathy, an autosomal-dominant disease due to mutations in the transthyretin gene, often affects the heart and liver, and is treated best with a combined heart-liver transplantation (CHLT). Although it remains an uncommonly performed procedure, the number of patients undergoing CHLT is increasing. Because of the complexity associated with dual pathophysiology, CHLT poses an extraordinary challenge for anesthesia management. Either both heart and liver transplantation are performed on cardiopulmonary bypass (CPB); or heart transplantation is performed on CPB, followed by liver transplantation with venovenous bypass. Recent reports suggested that liver transplantation can be performed without bypass using the inferior vena cava-sparing technique. However, both bypass and caval sparing technique have their own complications. Here, we present the anesthesia management in a case of sequential heart-liver transplantation using a routine caval cross-clamp technique without venovenous bypass. A 48-year-old man complaining of chest tightness, chest pain, and shortness of breath was diagnosed with amyloid cardiomyopathy. Cardiac ultrasonography revealed thickening of ventricular walls and left ventricular systolic insufficiency (ejection fraction decreased from 46% to ∼20% in 6 months), which was refractory to medical therapy. Symptoms occurred repeatedly. Therefore, CHLT was planned. Heart transplantation was performed smoothly under general anesthesia and standard CPB. His heart functioned well with dobutamine and epinephrine infusion. Subsequently, the patient was weaned from CPB. Liver transplantation was planned using the piggyback procedure with the caval sparing technique. However, upon caval clamping, unexpected blood loss occurred. Clamping of the caval was tested followed by cross-clamping. Norepinephrine, epinephrine, and dobutamine were administered. After the hepatic vein was anastomosed, the clamp was released and nitroglycerin was administered. Hemodynamics was stable, and the patient was discharged after 37 days of hospitalization. The case indicates that CHLT could be performed using caval clamp without venovenous bypass in selected patients.

Circulation collapse caused by intracardiac thrombosis associated with tranexamic acid administration: A case report.

RATIONALE: Perioperative administration of tranexamic acid has been suggested to reduce bleeding and blood transfusion requirements in patients undergoing orthopedic surgery. Despite being sporadic, the potential risk for thrombotic complications cannot be ignored. However, intracardiac thrombosis associated with tranexamic acid administration is rare. We described a case of circulatory collapse caused by intracardiac thrombosis associated with tranexamic acid administration for a scheduled knee arthroplasty. PATIENT CONCERNS: A 62-year-old male patient was scheduled for a right knee arthroplasty. He had a history of hypertension and had undergone surgery for treatment of right femur fracture 30 years previously. Other than a high platelet count (498 × 109/L), results of laboratory investigations were within normal limits. The ultrasonic examination of both lower limbs showed no thrombosis. Upon sterilizing the surgical area, tranexamic acid (1.6 g) was intravenously administered after induction of anesthesia and intubation. Then the patient had a sudden circulatory collapse. Through cardiopulmonary resuscitation, the patient recovered spontaneous circulation. Transesophageal echocardiography revealed extensive thrombosis in the right atrium and ventricle. DIAGNOSIS: Circulation collapse caused by intracardiac thrombosis. INTERVENTIONS: Thrombolytic therapy was recommended after urgent multidisciplinary consultation. Thus, urokinase was administered intravenously. Fifty minutes after thrombolysis, the mass in ventricle disappeared. A shrunken mass was observed in the right atrium. After another half an hour, no abnormal echoes were seen in the right heart chambers. OUTCOMES: The patient was discharged after 43 days without any organ dysfunction. LESSONS: This case reminds clinicians that perioperative tranexamic acid administration may increase the risk of thrombosis, which needs focused attention from anesthesiologists. Prompt transesophageal echocardiography examination should be done to allow immediate diagnosis and effective thrombolysis therapy when unexplained cardiac arrest occurs during anesthesia.

Anesthetic management of lung transplantation in a patient with end-stage COVID-19 pneumonia: A case report.

RATIONALE: The COVID-19 pandemic is spreading around the world and the leading cause of death is rapidly progressive respiratory failure because of lung damage and consolidation. Lung transplantation is the last line of treatment for chronic end-stage lung diseases. There were several cases of lung transplantation reported in patients with COVID-19 pneumonia. However, anesthetic management of lung transplantation in this subpopulation is rare. We report the anesthetic and perioperative management of lung transplantation in a patient with COVID-19 pneumonia. PATIENT CONCERNS: A 70-year-old man with a 7-day history of fever was diagnosed with COVID-19 pneumonia. His throat swab was positive for COVID-19, but negative for other common viruses. Chest radiography showed multiple inflammatory foci in both lungs. By day 5, he presented respiratory distress. Computed tomography (CT) scan showed progressive deterioration of both lungs. Starting on day 7, SARS-CoV-2 RNA in bronchoalveolar lavage samples were continuously negative. However, his lung condition deteriorated. By day 17, a veno-venous extracorporeal membrane oxygenation (ECMO) was initiated. After 10 days of ECMO support, the patient's lung condition did not improve. CT scan revealed bilateral parenchymal consolidation with pulmonary fibrosis and hydrothorax. DIAGNOSIS: Irreversible lung function loss induced by COVID-19 pneumonia. INTERVENTIONS: Bilateral transplantation was performed because the patient's lung condition did not improve and CT scan revealed parenchymal consolidation with pulmonary fibrosis after 10 days of ECMO support. Thirty-six hours after the surgery, ECMO was discontinued. A percutaneous transluminal coronary angioplasty and a stent implantation were performed because of acute coronary syndrome and myocardial ischemia 4 days postoperatively. OUTCOMES: The patient remained hospitalized because of requirements for intermittent assisted ventilation via tracheostomy. LESSONS: This case further supports the consideration that lung transplantation can potentially be the successful therapy for these patients who have developed irreversible lung function lose due to COVID-19 pneumonia. However, most critical patients with COVID-19 are older individuals with various comorbidities, which present new anesthetic challenges.

Effect of ultrasound-guided transversus abdominis plane block with rectus sheath block on patients undergoing laparoscopy-assisted radical resection of rectal cancer: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Many patients complain of pain following laparoscopic surgery. Clinicians have used ultrasound-guided posterior transversus abdominis plane block (TAPB) and rectus sheath block (RSB) for multimodal analgesia after surgery. We investigated the analgesic effects of US-guided posterior TAPB with RSB on postoperative pain following laparoscopy-assisted radical resection of early-stage rectal cancer. METHODS: Seventy-eight adults scheduled for laparoscopy-assisted radical resection of rectal cancer were enrolled in this double-blind placebo-controlled trial. Patients were randomized into 3 groups: the TR Group underwent US-guided bilateral posterior TAPB (40 mL 0.33% ropivacaine) with RSB (20 mL 0.33% ropivacaine); the T Group underwent US-guided bilateral posterior TAPB alone; and the Control Group received saline alone. All patients also had access to patient-controlled intravenous analgesia (PCIA) with sufentanil. The primary outcome was postoperative sufentanil consumption at 0-24, 24-48, and 48-72 h. The secondary outcomes were postoperative pain intensity and functional activity score at rest and while coughing for the same three time periods, intraoperative medication dosage, use of rescue analgesia, recovery parameters, and adverse effects. RESULTS: The three groups had no significant differences in baseline demographic and perioperative data, use of intraoperative medications, recovery parameters, and adverse effects. The TR group had significantly lower postoperative use of PCIA and rescue analgesic than in the other two groups (P < 0.05), but the Control Group and T Group had no significant differences in these outcomes. CONCLUSIONS: Postoperative US-guided posterior TAPB with RSB reduced postoperative opioid use in patients following laparoscopy-assisted radical resection of rectal cancer. TRIAL REGISTRATION: The trial was registered with chictr.org (ChiCTR2000029326) on January 25, 2020.

CXCR3 contributes to neuropathic pain via ERK activation in the anterior cingulate cortex.

The anterior cingulate cortex (ACC) is activated by noxious stimuli and is involved in the affective component of pain processing; but its role in the sensory component of pain remains largely unknown. Studies have verified that Chemokine (C-X-C motif) receptor 3 (CXCR3) is involved in nociceptive sensitization in the spinal cord after peripheral nerve injury; however, the expression of CXCR3 in the ACC and its role in neuropathic pain has not been reported. Here, we showed that CXCR3 co-localized with neurons in the ACC and the upregulation of CXCR3 corresponded with hypersensitive behaviors after a chronic constriction injury of the sciatic nerve. Pharmacological blockade of CXCR3 using local injection of its inhibitor, AMG487, into the ACC significantly attenuated hyperalgesia induced by chronic constriction injury and suppressed the phosphorylation of extracellular signal-regulated kinase (ERK). Collectively, these results suggest that CXCR3 in the ACC is involved in hyperalgesia induced by peripheral nerve injury and ERK may be a downstream target.

[Anesthesia management in cesarean section for patient with COVID-19: a case report].

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.

C-X-C Motif Chemokine 10 Contributes to the Development of Neuropathic Pain by Increasing the Permeability of the Blood-Spinal Cord Barrier.

Neuropathic pain is among the most debilitating forms of chronic pain. Studies have suggested that chronic pain pathogenesis involves neuroimmune interactions and blood-spinal cord barrier (BSCB) disruption. However, the underlying mechanisms are poorly understood. We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. We detected CXCR3 expression in spinal neurons and observed that CCI induced CXCL10/CXCR3 activation, BSCB disruption, and mechanical hyperalgesia. CCI-induced BSCB disruption enabled circulating T cells to migrate into the spinal parenchyma. Intrathecal administration of an anti-CXCL10 antibody not only attenuated CCI-induced hyperalgesia, but also reduced BSCB permeability, suggesting that CXCL10 acts as a key regulator of BSCB integrity. Moreover, T cell migration may play a critical role in the neuroimmune interactions involved in the pathogenesis of CCI-induced neuropathic pain. Our results highlight CXCL10 as a new potential drug target for the treatment of nerve injury-induced neuropathic pain.

Resection of the gastric submucosal tumor (G-SMT) originating from the muscularis propria layer: comparison of efficacy, patients' tolerability, and clinical outcomes between endoscopic full-thickness resection and surgical resection.

BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) has been increasingly applied in the treatment of gastric submucosal tumors (G-SMTs) with explorative intention. This study aimed to compare the efficacy, tolerability, and clinical outcomes of EFTR and surgical intervention for the management of muscularis propria (MP)-derived G-SMTs. METHODS: Between September 2011 and May 2019, the clinical records of patients with MP-derived G-SMTs undergoing EFTR at our endoscopic unit were collected. A cohort of people with primary MP-derived G-SMTs treated by surgery was matched in a 1:1 ratio to EFTR group with regard to patients' baseline characteristics, clinicopathologic features of the tumor and the procedure date. The perioperative outcomes and follow-up data were analyzed. RESULTS: In total, 62 and 62 patients were enrolled into the surgery and EFTR group, respectively, with median follow-up of 786 days. The size of G-SMTs (with ulceration) ranged from 10 to 90 mm. For patients with tumor smaller than 30 mm, surgery and EFTR group presented comparable procedural success rate (both were 100%), en bloc resection rate (100% vs. 94.7%), tumor capsule rupture rate (0% vs. 5.3%), and pathological R0 resection rate (both were 100%). EFTR had a statistically significant advantage over surgery for estimated blood loss (3.12 ± 5.20 vs. 46.97 ± 60.73 ml, p ≤ 0.001), discrepancy between the pre- and postprocedural hemoglobin level (5.18 ± 5.43 vs. 9.84 ± 8.25 g/L, p = 0.005), bowel function restoration [1 (0-5) vs. 3 (1-5) days, p ≤ 0.001], and hospital cost (28,617.09 ± 6720.78 vs. 33,963.10 ± 13,454.52 Yuan, p = 0.033). The patients with tumor larger than 30 mm showed roughly the same outcomes after comparison analysis of the two groups. However, the clinical data revealed lower en bloc resection rate (75.0% vs. 100%, p = 0.022) and higher tumor capsule rupture rate (25.0% vs. 0%, p = 0.022) for EFTR when compared to surgery. The procedure time, duration of postprocedural fasting and antibiotics usage, and hospital stay of the two groups were equivalent. The occurrence rate of adverse events within postoperative day 7 were 74.2% and 72.6% after EFTR and surgery, respectively (p = 1.000). No complications occurred during the follow-up. CONCLUSION: For treatment of MP-derived G-SMTs (with or without ulceration), our study showed the feasibility and safety of EFTR, which also provided better results in terms of procedural blood loss, the postoperative bowel function restoration and cost-effectiveness when compared to surgery, whereas the surgery was superior in en bloc resection rate for G-SMTs larger than 30 mm. The postprocedural clinical outcomes seemed to be equivalent in these two resection methods.

Epidural anesthesia for emergency cesarean section in a woman with Fontan circulation: A case report.

RATIONALE: Anesthetic management of pregnant women with Fontan circulation remains challenging. There are few reports that describe the anesthetic management of cesarean section after Fontan surgery. Here, we present a case of successful epidural anesthesia in a woman with Fontan circulation who required emergency cesarean section. PATIENT CONCERNS: A 29-year-old woman at gestational week 28 was scheduled for emergency cesarean section because of fetal distress. Her past medical history was significant for congenital transposition of the great arteries that had been treated by Fontan surgery 26 years earlier. Her postoperative course had been uneventful and she had reached a near normal level of activity with no arrhythmias or thrombotic complications. On presentation, her oxygen saturation was approximately 84% and she had digital clubbing. Arterial blood gas analysis showed a PCO2 of 35 mmHg, PO2 of 55.5 mmHg, and hemoglobin of 16.3 g/dL. Her blood coagulation parameters were within normal limits except for a high fibrinogen concentration (4.55 g/L). DIAGNOSIS: The diagnosis was pregnancy requiring emergency cesarean section because of fetal distress. INTERVENTIONS: Before anesthesia, a radial artery line was established for continuous measurement of blood pressure. An air pressure pump was placed on the patient's lower limbs and a low-dose dobutamine infusion was started. Next, epidural anesthesia was successfully performed at L2-3. Five milliliters of 2% lidocaine followed by 10 mL of 0.75% ropivacaine were injected. Dobutamine was infused to maintain a target blood pressure of 100-120/60-70 mmHg. OUTCOMES: The procedure was uneventful with the patient maintaining a stable heart rate of 80 to 90 beats/min and an oxygen saturation of 90% to 94%. A male infant weighing 840 g was delivered. The Apgar score was 9 at 1 and 5 minutes. The patient was transferred to the intensive care unit for 20 hours of monitoring and discharged 9 days later. The neonate was discharged after 2 months of specialist neonatal treatment. LESSONS: Epidural anesthesia may be used in women with Fontan circulation undergoing emergency cesarean section. Knowledge of the physiology of the heart lesion and that of pregnancy are critical to the outcome.

Intra-amygdala infusion of zeta inhibitory peptide attenuates neuropathic pain but not inflammatory pain in adult rats.

BACKGROUND: Protein kinase Mζ (PKMζ), a typical brain-specific PKC isoform, has been shown to be critical in the maintenance of long-term potentiation and memory storage. Zeta inhibitory peptide (ZIP), a peptide with selective inhibition of PKMζ, has been used in relieving experimental neuropathic pain and disrupting memory. The aim of this study was to investigate the effects of intra-amygdalar infusion of ZIP on neuropathic pain induced by chronic constriction injury (CCI), and inflammatory pain induced by complete Freund's adjuvant (CFA) in adult rats. METHODS: (I) ZIP was infused into the amygdala 30 minutes (min) before CCI was performed. Mechanical withdrawal threshold (MWT) was determined prior to the infusion of ZIP, and 30, 60, 90, 120, 150, 180 min after CCI (n=8 per group). (II) ZIP was infused into the amygdala 3, 7, 14 days after CCI (n=8 per group). MWT was measured 30 min before the infusion and 2, 12, 24 h after the infusion. (III) Three days after CCI, ZIP was infused into the amygdala repeatedly once a day for 2 days. MWT was measured before each infusion and 2 or 24 h after each infusion (n=8 per group). (IV) ZIP was infused into the amygdala 24 h after the establishment of inflammatory pain induced by complete Freund's adjuvant (CFA). MWT was determined 30 min before the infusion and 30, 60, 90, 120 and 150 min after the infusion (n=8 per group). RESULTS: As shown in figures, (I) amygdalar infusion of ZIP prior to the CCI produced no effect on CCI-induced hyperalgesia when compared to scr-ZIP or saline infusion [n=8, interaction effect, F (7.312, 76.776) =1.237, P>0.05; time as main factor, F (3.656, 76.776) =115.346, P<0.001; group as main factor, F (2, 21) =0.648, P>0.05]. (II) BLA infusion of ZIP significantly increased mechanical withdrawal threshold 7 days after CCI [n=8, interaction effect, F (5.476, 57.500) =15.279, P<0.001; time as main factor, F (2.738, 57.500) = 242.357, P<0.001; group as main factor, F (2,21) =4.786, P<0.05], just the same as 3 and 14 days after CCI (data not shown). (III) Bilateral injection of ZIP into the BLA significantly reduced mechanical hyperalgesia 2 h after the administration [n=8, paired t-test, t (0.05,7) =-5.561, P<0.05; n=8, paired t-test, t (0.05,7) =-4.745, P<0.05], and returned to baseline 24 h after the administration [n=8, paired t-test, t (0.05,7) =1.039, P>0.05; n=8, paired t-test, t (0.05,7) =-1.173, P>0.05]. (IV) ZIP produced no effect on mechanical withdrawal thresholds at all time points examined after the infusion, compared with scr-ZIP or saline control groups (n=8, interaction effect, F (6.135, 126) =1.724, P>0.05; group as main factor, F (2,21) =0.608, P>0.05). CONCLUSIONS: Intra-amygdala infusion of ZIP attenuates mechanical hyperalgesia induced by CCI but has no effect on inflammatory pain induced by CFA in rats, suggesting that amygdala PKMζ may be a therapeutic target in the treatment of neuropathic pain.

Function and mechanism of pyrin and IL-10 in the regulation of the inflammasome in pulmonary vascular endothelial cells following hemorrhagic shock.

The present study aimed to evaluate the function of pyrin and interleukin-10 (IL-10) and the potential mechanisms underlying the regulation of inflammation in pulmonary vascular endothelial cells (ECs) following hemorrhagic shock (HS). Adult female Sprague-Dawley rats were divided into 4 groups (n=6 in each group) to examine the changes in pyrin expression following HS-lipopolysaccharide (LPS) administration, including the following groups: A sham operation (SM) + tracheal injection of saline (SAL) group; a HS + SAL group; a SM + LPS group (with a tracheal injection of endotoxin); and a HS + LPS group. An additional 4 groups were used to evaluate the function of IL-10, by the additional intratracheal injection of recombinant IL-10. Western blot analysis and immunofluorescence were performed in order to investigate the changes to pyrin and IL-10 expression in pulmonary vascular ECs. The expression levels of pyrin in the SM + LPS group were significantly increased in comparison with the SM + SAL group (P<0.01). Additionally, the expression levels of pyrin were significantly increased in the HS + LPS group compared with the HS + SAL group (P<0.01). The expression levels of caspase-1 were significantly increased in the HS + LPS group compared with those in the other three groups (P<0.01). The expression levels of pyrin in the HS + LPS + IL-10 group were significantly increased compared with the HS + LPS group (P<0.01). The expression levels of caspase-1 were significantly decreased following IL-10 treatment compared with those in the HS + LPS group (P<0.01). Therefore, HS attenuated LPS-induced pyrin expression in pulmonary vascular ECs and may also inhibit the expression of IL-10, resulting in the activation of caspase-1 subsequent to a second LPS insult.

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal ß-catenin in chronic constriction injury rats.

BACKGROUND AND OBJECTIVES: Pulsed radiofrequency (PRF) is a minimal neurodestructive interventional pain therapy. However, its analgesic mechanism remains largely unclear. We aimed to investigate the peripheral and spinal mechanisms of PRF applied either adjacent to the ipsilateral L5 dorsal root ganglion (PRF-DRG) or PRF to the sciatic nerve (PRF-SN) in the neuropathic pain behavior induced by chronic constriction injury (CCI) in rats. METHODS: On day 0, CCI or sham surgeries were performed. Rats then received either PRF-DRG, PRF-SN, or sham PRF treatment on day 4. Pain behavioral tests were conducted before surgeries and on days 1, 3, 5, 7, 9, 11, 13, and 14. After the behavioral tests, the rats were sacrificed. The venous blood or sciatic nerve samples were collected for ELISAs and the dorsal horns of the L4-L6 spinal cord were collected for western blot examination. RESULTS: The mechanical allodynia and the thermal hyperalgesia has been relieved by a single PRF-DRG or PRF-SN application. In addition, the analgesic effect of PRF-DRG was superior to PRF-SN on CCI-induced neuropathic pain. Either PRF-DRG or PRF-SN reversed the enhancement of interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels in the blood of CCI rats. PRF-DRG or PRF-SN also downregulated spinal ß-catenin expression. CONCLUSIONS: PRF treatment either to DRG or to sciatic nerve reduced neuropathic pain behavior, and reduced peripheral levels of pro-inflammatory cytokines and spinal ß-catenin expression in CCI rats. PRF to DRG has a better analgesic effect than PRF to the nerve.

Mast cell stabilizer ketotifen reduces hyperalgesia in a rodent model of surgically induced endometriosis.

Purpose: This study aimed to investigate the effect of oral treatment with ketotifen, a mast cell (MC) stabilizer, in a rat model of surgically induced endometriosis. Methods: At 14 days after Sprague-Dawley rats had surgery, they were treated with ketotifen (1 or 10 mg/kg/day). Pain behaviors were evaluated 3 days prior to surgery and then at 7, 14, 21, and 28 days after surgery. At day 28, rats were sacrificed and all samples were then processed for biochemical studies. Results: We found that ketotifen-treated rats showed significantly shorter duration of hyperalgesia (p<0.05); smaller cyst diameter (p<0.05) and lower histopathologic score (p<0.001); significantly lower MC number and degranulation (p<0.001), blood vessel number (p<0.001), lower expression levels of nerve growth factor (p<0.001), cyclooxygenase-2 (p<0.001), intercellular cell adhesion molecule-1 (p<0.001), and vascular endothelial growth factor (p<0.05) in cysts, and nerve growth factor (p<0.001) and transient receptor potential cation channel, subfamily V, member 1 (p<0.001) in dorsal root ganglia; and lower histamine (p<0.05) and tumor necrosis factor-alpha (p<0.05) concentrations in serum compared with placebo-treated animal subjects. Conclusion: Oral treatment with ketotifen significantly suppressed the development of hyperalgesia, probably by modulating MC activity in cysts, thereby reducing peripheral sensitization due to noxious signals from endometriotic lesions. Our results suggest that ketotifen may inhibit the development of endometriotic lesions and hyperalgesia in rats.