Downregulation of lncRNA FIRRE relieved the neuropathic pain of female mice by suppressing HMGB1 expression.

Long non-coding RNAs are novel regulators in neuropathic pain. In this study, we aimed to explore the role and the mechanism of lncRNA FIRRE in regulating the secretion of microglial cells-derived proinflammatory cytokines in neuropathic pain. The female mouse model of neuropathic pain was established by bilateral chronic constriction injury (CCI) surgery. The mouse primary microglial cells were induced by lipopolysaccharide (LPS). The interaction between FIRRE and high mobility group box 1 (HMGB1) was assessed by RNA immunoprecipitation, RNA pull-down, and ubiquitination assays. FIRRE expression was upregulated in the spinal cord tissue of female CCI mice and LPS-induced microglial cells. The concentrations of IL-1ß, TNF-α, and IL-6 from LPS-induced microglial cells were reduced by FIRRE knockdown. FIRRE bound to HMGB1 and negatively regulated its protein level. The ubiquitination degradation of HMGB1 was promoted by FIRRE silence. The HMGB1 over-expression reversed the inhibitory effect of FIRRE silence on the secretion of IL-1ß, TNF-α, and IL-6 from LPS-induced microglial cells. The in vivo experiment showed that FIRRE knockdown alleviated neuropathic pain of CCI female mice. Our findings indicated that lncRNA FIRRE downregulation inhibits the secretion of microglial cells-derived proinflammatory cytokines by decreasing HMGB1 expression, thereby relieving neuropathic pain of female mice.

MZF1 in the Dorsal Root Ganglia Contributes to the Development and Maintenance of Neuropathic Pain via Regulation of TRPV1.

Previous studies have demonstrated that myeloid zinc finger 1 (MZF1) in the dorsal root ganglion (DRG) participates in neuropathic pain induced by chronic-constriction injury (CCI) via regulation of voltage-gated K+ channels (Kv). Emerging evidence indicates that transient receptor potential vanilloid 1 (TRPV1) is involved in the development and maintenance of neuropathic pain. Although it is known that the transcription of TRPV1 is regulated by Kruppel-like zinc-finger transcription factor 7 (Klf7)-and that the structure of TRPV1 is similar to that of Kv-few studies have systematically investigated the relationship between MZF1 and TRPV1 in neuropathic pain. In the present study, we demonstrated that CCI induced an increase in MZF1 and TRPV1 in lumbar-level 4/5 (L4/5) DRGs at 3 days post-CCI and that this increase was persistent until at least 14 days post-CCI. DRG microinjection of rAAV5-MZF1 into the DRGs of naïve rats resulted in a decrease in paw-withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared with that of the rAAV5-EGFP group, which started at four weeks and lasted until at least eight weeks after microinjection. Additionally, prior microinjection of MZF1 siRNA clearly ameliorated CCI-induced reduction in PWT and PWL at 3 days post-CCI and lasted until at least 7 days post-CCI. Correspondingly, microinjection of MZF1 siRNA subsequent to CCI alleviated the established mechanical allodynia and thermal hyperalgesia induced by CCI, which occurred at 3 days postinjection and lasted until at least 10 days postinjection. Microinjection of rAAV5-MZF1 increased the expression of TRPV1 in DRGs. Microinjection of MZF1 siRNA diminished the CCI-induced increase of TRPV1, but not P2X7R, in DRGs. These findings suggest that MZF1 may contribute to neuropathic pain via regulation of TRPV1 expression in DRGs.

Myeloid-derived suppressor cells suppress CD4+ T cell activity and prevent the development of type 2 diabetes.

CD4+ T cells play an important role in the progression of type 2 diabetes mellitus (T2DM). It is known that T cell responses can be suppressed by myeloid-derived suppressor cells (MDSCs). In this study, we aimed to explore the potential role of MDSCs in the progression of T2DM, and to examine whether the underlying mechanism was associated with CD4+ T cells. Peripheral blood samples were obtained from T2DM patients and healthy controls, as well as C57BL6J db/db mice and control heterozygous (db/-) mice. The frequency of MDSCs and CD4+ T cells was analyzed using flow cytometry. Serum levels of the cytokines interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were quantified using ELISA kits. Cell proliferation was assessed using carboxyfluorescein succinimidyl ester (CFSE) labeling. In addition, the severity of insulitis was assessed using H&E staining of the pancreata. The data showed an increased frequency of CD11b+/CD33+ MDSCs and CD4+ T cells in the peripheral blood of T2DM patients. In addition, there were decreased IL-4 level and increased TNF-α and IFN-γ levels in the serum from T2DM patients. In db/db mice, an increased frequency of CD11b+/Gr-1+ MDSCs and CD4+ T cells was found in splenocytes, as well as in the peripheral blood. MDSCs inhibited the proliferation and modulated the cytokine secretion of CD4+ T cells in vitro and delayed the development of diabetes in NOD/SCID mice. In conclusion, MDSCs suppress CD4+ T cell activity and prevent the development of T2DM.

Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study.

Background: Frailty has been associated with mental illness (MI) observational studies, but the causal relationship between these factors remains uncertain. We aimed to assess the bidirectional causality between frailty and MI by two-sample Mendelian randomization (MR) analyses. Methods: To investigate the causal relationship among them, summary statistics of frailty index (FI) and six types of MI: anxiety, depression, affective disorder, mania, schizophrenia, and obsessive-compulsive disorder (OCD) were included in this MR study. This MR analysis was performed using inverse variance weighting (IVW), MR-Egger regression, and weighted median. The stability of the results was evaluated using Cochran's Q test, MR-Egger intercept test, Funnel Plots, and leave-one-out analysis. Results: Genetic predisposition to FI was significantly associated with increased anxiety (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.13-2.33, P = 8.18E-03), depression (OR = 1.88, 95% CI 1.30-2.71, P = 8.21E-04), affective disorder (OR = 1.70, 95% CI 1.28-2.27, P = 2.57E-04). However, our study findings do not demonstrate a causal relationship between FI and mania (OR = 1.02, 95% CI 0.99-1.06, P = 2.20E-01), schizophrenia (OR = 1.02, 95% CI 0.07-0.86, P = 9.28E-01). In particular, although the IVW results suggest a potential causal relationship between FI and OCD (OR = 0.64, 95% CI 0.07-0.86, P = 2.85E-02), the directions obtained from the three methods we employed ultimately show inconsistency. Therefore, the result must be interpreted with caution. The results of the reverse MR analysis indicated a statistically significant and causal relationship between anxiety (OR = 1.06, 95% CI 1.01-1.11, P = 2.00E-02), depression (OR = 1.14, 95% CI 1.04-1.26, P = 7.99E-03), affective disorder (OR = 1.15, 95% CI 1.09-1.21, P = 3.39E-07), and schizophrenia (OR = 1.02, 95% CI 1.01-1.04, P = 1.70E-03) with FI. However, our findings do not provide support for a link between mania (OR = 1.46, 95% CI 0.79-2.72, P = 2.27E-01), OCD (OR = 1.01, 95% CI 1.00-1.02, P = 2.11E-01) and an increased risk of FI. Conclusion: The MR results suggest a potential bidirectional causal relationship between FI and anxiety, depression, and affective disorder. Schizophrenia was found to be associated with a higher risk of FI. The evidence was insufficient to support a causal relationship between Fl and other Ml. These findings offer new insights into the development of effective management strategies for frailty and MI.

Nanozymes: Potential Therapies for Reactive Oxygen Species Overproduction and Inflammation in Ischemic Stroke and Traumatic Brain Injury.

Nanozymes, which can selectively scavenge reactive oxygen species (ROS), have recently emerged as promising candidates for treating ischemic stroke and traumatic brain injury (TBI) in preclinical models. ROS overproduction during the early phase of these diseases leads to oxidative brain damage, which has been a major cause of mortality worldwide. However, the clinical application of ROS-scavenging enzymes is limited by their short in vivo half-life and inability to cross the blood-brain barrier. Nanozymes, which mimic the catalytic function of natural enzymes, have several advantages, including cost-effectiveness, high stability, and easy storage. These advantages render them superior to natural enzymes for disease diagnosis and therapeutic interventions. This review highlights recent advancements in nanozyme applications for ischemic stroke and TBI, emphasizing their potential to mitigate the detrimental effect of ROS overproduction, oxidative brain damage, inflammation, and blood-brain barrier compromise. Therefore, nanozymes represent a promising treatment modality for ROS overproduction conditions in future medical practices.

Neutrophil autophagy and NETosis in COVID-19: perspectives.

The COVID-19 pandemic has caused substantial losses worldwide in people's lives, health, and property. Currently, COVID-19 is still prominent worldwide without any specific drug treatment. The SARS-CoV-2 pathogen is the cause of various systemic diseases, mainly acute pneumonia. Within the pathological process, neutrophils are recruited to infected sites, especially in the lungs, for the first stage of removing invading SARS-CoV-2 through a range of mechanisms. Macroautophagy/autophagy, a conserved autodegradation process in neutrophils, plays a crucial role in the neutrophil phagocytosis of pathogens. NETosis refers to neutrophil cell death, while auto-inflammatory factors and antigens release NETs. This review summarizes the latest research progress and provides an in-depth explanation of the underlying mechanisms of autophagy and NETosis in COVID-19. Furthermore, after exploring the relationship between autophagy and NETosis, we discuss potential targets and treatment options. This review keeps up with the latest research on COVID-19 from neutrophil autophagy and NETosis with a new perspective, which can guide the urgent development of antiviral drugs and provide guidance for the clinical treatment of COVID-19.Abbreviations: AKT1: AKT serine/threonine kinase 1; AMPK: AMP-activated protein kinase; AP: autophagosome; ARDS: acute respiratory distress syndrome; ATG: autophagy related; BECN1: beclin 1; cfDNA: cell-free DNA; COVID-19: coronavirus disease 2019; CQ: chloroquine; DMVs: double-membrane vesicles; ELANE/NE: elastase, neutrophil expressed; F3: coagulation factor III, tissue factor; HCQ: hydroxychloroquine; MAP1LC3/LC3: microtubule associated protein 1 light chain of 3; MPO: myeloperoxidase; MTORC1: mechanistic target of rapamycin kinase complex 1; NETs: neutrophil traps; NSP: nonstructural protein; PI3K: class I phosphoinositide 3-kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SKP2: S-phase kinase associated protein 2; TCC: terminal complement complex; ULK1: unc-51 like.

Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies.

The metabolism of L-tryptophan (TRP) regulates homeostasis, immunity, and neuronal function. Altered TRP metabolism has been implicated in the pathophysiology of various diseases of the central nervous system. TRP is metabolized through two main pathways, the kynurenine pathway and the methoxyindole pathway. First, TRP is metabolized to kynurenine, then kynurenic acid, quinolinic acid, anthranilic acid, 3-hydroxykynurenine, and finally 3-hydroxyanthranilic acid along the kynurenine pathway. Second, TRP is metabolized to serotonin and melatonin along the methoxyindole pathway. In this review, we summarize the biological properties of key metabolites and their pathogenic functions in 12 disorders of the central nervous system: schizophrenia, bipolar disorder, major depressive disorder, spinal cord injury, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Furthermore, we summarize preclinical and clinical studies, mainly since 2015, that investigated the metabolic pathway of TRP, focusing on changes in biomarkers of these neurologic disorders, their pathogenic implications, and potential therapeutic strategies targeting this metabolic pathway. This critical, comprehensive, and up-to-date review helps identify promising directions for future preclinical, clinical, and translational research on neuropsychiatric disorders.

Blocking autofluorescence in brain tissues affected by ischemic stroke, hemorrhagic stroke, or traumatic brain injury.

Autofluorescence is frequently observed in animal tissues, interfering with an experimental analysis and leading to inaccurate results. Sudan black B (SBB) is a staining dye widely used in histological studies to eliminate autofluorescence. In this study, our objective was to characterize brain tissue autofluorescence present in three models of acute brain injury, including collagenase-induced intracerebral hemorrhage (ICH), traumatic brain injury (TBI), and middle cerebral artery occlusion, and to establish a simple method to block autofluorescence effectively. Using fluorescence microscopy, we examined autofluorescence in brain sections affected by ICH and TBI. In addition, we optimized a protocol to block autofluorescence with SBB pretreatment and evaluated the reduction in fluorescence intensity. Compared to untreated, pretreatment with SBB reduced brain tissue autofluorescence in the ICH model by 73.68% (FITC), 76.05% (Tx Red), and 71.88% (DAPI), respectively. In the TBI model, the ratio of pretreatment to untreated decreased by 56.85% (FITC), 44.28% (Tx Red), and 46.36% (DAPI), respectively. Furthermore, we tested the applicability of the protocol using immunofluorescence staining or Cyanine-5.5 labeling in the three models. SBB treatment is highly effective and can be applied to immunofluorescence and fluorescence label imaging techniques. SBB pretreatment effectively reduced background fluorescence but did not significantly reduce the specific fluorescence signal and greatly improved the signal-to-noise ratio of fluorescence imaging. In conclusion, the optimized SBB pretreatment protocol blocks brain section autofluorescence of the three acute brain injury models.

Cav3.2 T-Type calcium channels downregulation attenuates bone cancer pain induced by inhibiting IGF-1/HIF-1α signaling pathway in the rat spinal cord.

Background: Bone cancer pain (BCP) is one of the most ubiquitous and refractory symptoms of cancer patients that needs to be urgently addressed. Substantial studies have revealed the pivotal role of Cav3.2 T-type calcium channels in chronic pain, however, its involvement in BCP and the specific molecular mechanism have not been fully elucidated. Methods: The expression levels of Cav3.2, insulin-like growth factor 1(IGF-1), IGF-1 receptor (IGF-1R) and hypoxia-inducible factor-1α (HIF-1α) were detected by Western blot in tissues and cells. X-ray and Micro CT used to detect bone destruction in rats. Immunofluorescence was used to detect protein expression and spatial location in the spinal dorsal horn. Electrophoretic mobility shift assay used to verify the interaction between HIF-1α and Cav3.2. Results: The results showed that the expression of Cav3.2 channel was upregulated and blockade of this channel alleviated mechanical allodynia and thermal hyperalgesia in BCP rats. Additionally, inhibition of IGF-1/IGF-1R signaling not only reversed the BCP-induced upregulation of Cav3.2 and HIF-1α, but also decreased nociceptive hypersensitivity in BCP rats. Inhibition of IGF-1 increased Cav3.2 expression levels, which were abolished by pretreatment with HIF-1α siRNA in PC12 cells. Furthermore, nuclear HIF-1α bound to the promoter of Cav3.2 to regulate the Cav3.2 transcription level, and knockdown of HIF-1α suppresses the IGF-1-induced upregulation of Cav3.2 and pain behaviors in rats with BCP. Conclusion: These findings suggest that spinal Cav3.2 T-type calcium channels play a central role during the development of bone cancer pain in rats via regulation of the IGF-1/IGF-1R/HIF-1α pathway.

Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications.

Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways. This article provides an overview of the enriched environment protocols used in animal models of ischemic stroke, ICH, and TBI, as well as relevant clinical studies, with a particular focus on ischemic stroke. Additionally, we explored studies of animals with stroke and TBI exposed to EE alone or in combination with multiple drugs and other rehabilitation modalities. Finally, we discuss the potential clinical applications of EE in future brain rehabilitation therapy and the molecular and cellular changes caused by EE in rodents with stroke or TBI. This article aims to advance preclinical and clinical research on EE rehabilitation therapy for acquired brain injury. © 2024 American Physiological Society. Compr Physiol 14:5291-5323, 2024.

The role of botulinum toxin type A related axon transport in neuropathic pain induced by chronic constriction injury.

Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats. Methods: Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots. Results: The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats. Conclusions: BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.

Meckel's Cave Size Measured by Magnetic Resonance Imaging in the Prognosis of Percutaneous Balloon Compression for Trigeminal Neuralgia.

BACKGROUND: Percutaneous balloon compression (PBC) is a safe and effective method to treat trigeminal neuralgia. Despite it is known that intraoperative balloon volume is crucial in the prognosis of PBC patients and correlates with Meckel's cave (MC) size, it is a lack of objective and valid criteria for intraoperative balloon volume of PBC. OBJECTIVES: The aim of this study was to evaluate the relationship between the size of MC and the volume of a pear-shaped balloon in improving the prognosis of patients receiving PBC. STUDY DESIGN: Retrospective study. METHODS: Patients were divided into 3 groups according to their prognosis, and simple linear regression equations were established separately. Group A was defined as having recurrence. Group B was defined as having no recurrence and a Barrow Neurological Institute facial numbness (BNI-N) score of 2 with no recurrence. Correlation analysis was carried out to determine the association of the intraoperative balloon volume with MC size. We attempted to construct simple linear regression models after verifying that both parameters were in compliance with the requirements of this model. RESULTS: Until the end of the 6-months follow-up, 60 patients (93.8%) reported no pain, and 4 patients (6.3%) experienced no significant pain relief. Sixteen (25.0%) patients had severe facial numbness, 48 (75.0%) patients had no facial numbness or had only mild numbness. All 3 groups had a significant correlation between balloon volume and MC size. Group A: Balloon volume (cm3) = -0.371 + 1.883*MC size (R2 = 0.882); Group B: Balloon volume (cm3) = 0.110 + 1.274*MC size (R2 = 0.861); and Group C: Balloon volume (cm3) = 0.011 + 1.835*MC size (R2 = 0.857). LIMITATIONS: The main limitation of our study is its observational retrospective nature, and we were unable to further analyze the intraoperative balloon pressure and volume, as well as validate the accuracy of the model. In additional this was a single-center study with a small sample size and a short follow-up period. These may have contributed to the bias in the final results. A multicenter, prospective study with a large sample size should be performed to further investigate the long-term effects of individualized balloon volumes and the correlation between pressures. CONCLUSIONS: The equation [balloon volume (cm3) = 0.110 cm3 + 1.274*MC size] yields an appropriate value at which the patient has a low recurrence rate and a low degree of facial numbness. Preoperative measurement of MC size can be used to guide the intraoperative balloon volume and to predict the patient's prognosis.

Comparison of the Efficacy of Short-term Peripheral Nerve Stimulation and Pulsed Radiofrequency for Treating Herpes Zoster Ophthalmicus Neuralgia.

OBJECTIVE: This study aimed to investigate the effect of therapy with peripheral nerve stimulation (PNS) and pulsed radiofrequency (PRF) combined or PNS and PRF separately in patients with herpes zoster ophthalmicus (HZO). MATERIALS AND METHODS: This cohort study included 106 cases of HZO. Three groups were identified according to the type of treatment received: combination therapy (PNS+PRF) (n=38), PRF (n=37), and PNS (n=31). The observations at 0, 1, 2, and 4 weeks; 3 and 6 months; and 1 and 2 years after the operation were analyzed. Observations at each follow-up included baseline characteristics, Numerical Rating Scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI), concomitant pain medication usage, relapse rate, and adverse events. RESULTS: The postoperative NRS of all 3 groups were significantly lower than preoperative scores. The PSQI of the 3 groups was significantly improved postoperatively, and the concomitant pain medication gradually decreased. Regarding long-term efficacy, the pain NRS and PSQI scores of the PNS+PRF and PNS groups were significantly lower than those of the PRF group ( P <0.05), and the relapse rate of the PRF group was higher than that of the PNS+PRF and PNS groups ( P <0.05). No significant difference was observed between the PNS+PRF and the PNS groups. CONCLUSION: Both PNS and PRF treatment of HZO can decrease the pain score, yielding no serious complications. The combination of PNS and PRF or PNS alone resulted in more significant pain relief than treatment with PRF alone. Thus, PNS therapy may be a better treatment option for HZO.

Sleep deprivation and recovery sleep affect healthy male resident's pain sensitivity and oxidative stress markers: The medial prefrontal cortex may play a role in sleep deprivation model.

Sleep is essential for the body's repair and recovery, including supplementation with antioxidants to maintain the balance of the body's redox state. Changes in sleep patterns have been reported to alter this repair function, leading to changes in disease susceptibility or behavior. Here, we recruited healthy male physicians and measured the extent of the effect of overnight sleep deprivation (SD) and recovery sleep (RS) on nociceptive thresholds and systemic (plasma-derived) redox metabolism, namely, the major antioxidants glutathione (GSH), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD). Twenty subjects underwent morning measurements before and after overnight total SD and RS. We found that one night of SD can lead to increased nociceptive hypersensitivity and the pain scores of the Numerical Rating Scale (NRS) and that one night of RS can reverse this change. Pre- and post-SD biochemical assays showed an increase in MDA levels and CAT activity and a decrease in GSH levels and SOD activity after overnight SD. Biochemical assays before and after RS showed a partial recovery of MDA levels and a basic recovery of CAT activity to baseline levels. An animal study showed that SD can cause a significant decrease in the paw withdrawal threshold and paw withdrawal latency in rats, and after 4 days of unrestricted sleep, pain thresholds can be restored to normal. We performed proteomics in the rat medial prefrontal cortex (mPFC) and showed that 37 proteins were significantly altered after 6 days of SD. Current findings showed that SD causes nociceptive hyperalgesia and oxidative stress, and RS can restore pain thresholds and repair oxidative stress damage in the body. However, one night of RS is not enough for repairing oxidative stress damage in the human body.

Intraoperative Intravenous Infusion of Esmketamine Has Opioid-Sparing Effect and Improves the Quality of Recovery in Patients Undergoing Thoracic Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Postoperative thoracic surgery is often accompanied by severe pain, and opioids are a cornerstone of postoperative pain management, but their use may be limited by many adverse events. Several studies have shown that the perioperative application of esketamine adjuvant therapy can reduce postoperative opioid consumption. However, whether esketamine has an opioid-sparing effect after thoracic surgery is unclear. OBJECTIVES: To explore the opioid-sparing effect of different doses of esketamine infusion during thoracic surgery and its impact on patient recovery. STUDY DESIGN: Randomized controlled study. SETTING: A single-center study with a total of 120 patients. METHODS: Patients were randomly allocated to 1 or 3 groups receiving intraoperative intravenous infusions of esketamine 0.15 mg · kg-1· h-1 (group K1), esketamine 0.25 mg · kg-1· h-1(group K2), or placebo (group C). Postoperative opioid consumption, and postoperative indicators like extubation time, PACU stay time, and adverse events were recorded for each group. RESULTS: The consumption of hydromorphone during the first 24 and 48 postoperative hours was significantly reduced in patients of group K2 compared to those of group C and group K1. The time to extubation and post anesthesia care unit (PACU) stay were significantly shorter in group K2 than in group K1 and group C. The time to first feed and off the bed time after surgery were shorter in groups K1 and K2 than in group C. Patients in group K2 were significantly satisfied with patient controlled intravenous analgesia (PCIA) than in groups K1 and C. LIMITATIONS: The sample size calculation was based mainly on the index of hydromorphone consumption. CONCLUSIONS: Intraoperative intravenous esketamine at 0.25 mg · kg-1 · h-1 reduced postoperative opioids consumption by 34% in postoperative 24 hours and 30% in postoperative 48 hours in patients undergoing thoracic surgery. It also improved the quality of perioperative recovery.

Regulated necrosis in COVID-19: A double-edged sword.

COVID-19 caused by SARS-CoV-2 can cause various systemic diseases such as acute pneumonia with cytokine storm. Constituted of necroptosis, pyroptosis, and ferroptosis, regulated necrosis constitutes the cell death patterns under the low apoptosis condition commonly observed in COVID-19. Regulated necrosis is involved in the release of cytokines like TNF-α, IL-1 ß, and IL-6 and cell contents such as alarmins, PAMPs, and DAMPs, leading to more severe inflammation. Uncontrolled regulated necrosis may explain the poor prognosis and cytokine storm observed in COVID-19. In this review, the pathophysiology and mechanism of regulated necrosis with the double-edged sword effect in COVID-19 are thoroughly discussed in detail. Furthermore, this review also focuses on the biomarkers and potential therapeutic targets of the regulated necrosis pathway in COVID-19, providing practical guidance to judge the severity, prognosis, and clinical treatment of COVID-19 and guiding the development of clinical anti-SARS-CoV-2 drugs.

Chinese expert consensus on minimally invasive interventional treatment of trigeminal neuralgia.

Background and purpose: Trigeminal neuralgia is a common condition that is associated with severe pain, which seriously affects the quality of life of patients. When the efficacy of drugs is not satisfactory or adverse drug reactions cannot be tolerated, minimally invasive interventional therapy has become an important treatment because of its simple operation, low risk, high repeatability and low cost. In recent years, minimally invasive interventional treatments, such as radiofrequency thermocoagulation (RF) of the trigeminal nerve and percutaneous microcompression (PMC), have been widely used in the clinic to relieve severe pain in many patients, however, some related problems remain to be addressed. The Pain Association of the Chinese Medical Association organizes and compiles the consensus of Chinese experts to standardize the development of minimally invasive interventional treatment of trigeminal neuralgia to provide a basis for its clinical promotion and application. Materials and methods: The Pain Association of the Chinese Medical Association organizes the Chinese experts to compile a consensus. With reference to the evidence-based medicine (OCEBM) system and the actual situation of the profession, the Consensus Development Committee adopts the nominal group method to adjust the recommended level. Results: Precise imaging positioning and guidance are the keys to ensuring the efficacy and safety of the procedures. RF and PMC are the most widely performed and effective treatments among minimally invasive interventional treatments for trigeminal neuralgia. Conclusions: The pain degree of trigeminal neuralgia is severe, and a variety of minimally invasive intervention methods can effectively improve symptoms. Radiofrequency and percutaneous microcompression may be the first choice for minimally invasive interventional therapy.

Alterations in local activity and functional connectivity in patients with postherpetic neuralgia after short-term spinal cord stimulation.

Introduction: The efficacy of short-term spinal cord stimulation (stSCS) as a treatment for neuropathic pain in patients with postherpetic neuralgia (PHN) has already been validated. However, the potential alterations in brain functionality that are induced by such treatment have yet to be completely elucidated. Methods: This study use resting-state functional magnetic resonance imaging (rs-fMRI) to detect the changes in regional homogeneity (ReHo) and degree centrality (DC) related to stimulator-induced pain relief in patients with PHN. A total of 10 patients with PHN underwent an MRI protocol at baseline and after stSCS. Alterations in ReHo and DC were then compared between baseline and after stSCS. We investigated the relationship between clinical parameters and functional changes in the brain. Results: Clinical parameters on pain, emotion, and sleep quality were correlated with ReHo and DC. ReHo and DC were significantly altered in the middle temporal gyrus, precuneus, superior frontal gyrus, supramarginal gyrus, inferior parietal lobule, rolandic operculum, middle occipital gyrus, superior parietal gyrus, and the precentral gyrus after stSCS. A significant correlation was detected between ReHo changes in the middle occipital gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality. A significant negative correlation was detected between DC changes in the middle temporal gyrus, rolandic operculum, supramarginal gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality. Conclusion: This study found that stSCS is able to induce ReHo and DC changes in patients with PHN, thus suggesting that stSCS can change brain function to alleviate pain, sleep, and emotional disorder.

Short-term spinal cord stimulation is an effective therapeutic approach for herpetic-related neuralgia-A Chinese nationwide expert consensus.

Purpose: Short-term spinal cord stimulation (st-SCS) has been widely used to treat herpetic-related neuralgia (HN) in China for several years, but is still heavily debated as it has no strong evidence in clinical application. Therefore, a questionnaire survey among the Chinese pain specialist workgroup of the Chinese Neuromodulation Society and Chinese Medical Doctor Association was carried out to achieve a consensus about the clinical use of st-SCS for HN treatment. Methods: The contents of the questionnaire include basic information about doctors (hospital level, work experience, training, procedure numbers, etc.), efficacy, indications, and contraindications of st-SCS, operation conditions, and preoperative preparation of st-SCS, and the prospect of the st-SCS procedure. Initially, the survey was conducted on 110 experts who have practiced the st-SCS procedure from all over the provinces in China. Finally, valuable data was calculated from the 110 questionnaires excluding the doctors with <1 year of experience of st-SCS, <10 cases of procedures per year, and no standard training in SCS technique. Results: Based on the 110 questionnaires, it is estimated that 5,000 to 10,000 cases of electrical stimulation are carried out nationwide each year. Sixty-nine valid questionnaires acquired from senior pain physicians were more valuable and specialized in the efficacy, indications, and contraindications of st-SCS for HN. It was commonly agreed (97.10%) that the HN patients with <3 months will obtain good effectiveness (patient satisfaction rate ≥50%). Almost all (98.55%) agreed that st-SCS can be used in SHN patients, there was a common agreement (72.46%) that AHN patients are an indication of st-SCS, and more than half agreement (53.62%) that st-SCS may be fit for early PHN (3-6 months). A common agreement (79.71%) was achieved that more than half of HN patients had the experience of nerve block or nerve pulsed RF. A similarly large number of experts 57/69 (82.61%) agreed that an 80% paresthesia coverage should be achieved at the test stimulation and 57/69 (82.61%) agreed that the treatment of st-SCS need be persistent for 1-2 weeks. Conclusions: Early HN patients can get an effective outcome from the treatment of st-SCS and maybe the indication of st-SCS. Moreover, standardized training for pain physicians and basic research and clinical studies are warranted.

The Analysis of Percutaneous Balloon Compression on Efficacy and Negative Emotion in the Treatment of Recurrent Trigeminal Neuralgia After Surgical Procedures.

BACKGROUND: Recurrent trigeminal neuralgia (TN) after surgical operations can be quite difficult to treat, and treatment measures have not been standardized. Patients often have long-term, repeated severe pain, which may easily cause anxiety and depression and can exert a negative effect on the quality of life. Despite the known efficacy of percutaneous balloon compression (PBC) for TN, it is unclear whether PBC can be used as the preferred surgical treatment for postoperative recurrent TN and effectively improve patients' negative emotions. OBJECTIVES: This study aimed to evaluate the clinical curative effect of PBC in patients with postoperative recurrent TN and analyze the improvement in conditions such as anxiety, depression, and sleep disorders. STUDY DESIGN: Retrospective study. SETTING: Center of Pain Medicine, Department of Anesthesiology, pain, and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University. METHODS: Clinical data from 121 postoperative recurrent TN patients who underwent PBC between August 2017 and June 2019 were retrospectively reviewed and analyzed. The Barrow Neurological Institute pain intensity (BNI-P) score was used to measure the severity of pain. The Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate anxiety, depression, and sleep status. RESULTS: On postoperative day 1, 104 patients (86.0%) reported no pain, 9 patients (7.4%) had occasional pain that did not require medication, and 8 patients (6.6%) experienced no significant pain relief. The total efficacy was 93.4%. Moreover, 3 patients (2.5%) reported significant pain relief 2 weeks postoperatively. Within a follow-up time of 12 months, 101 (83.5%) patients remained pain-free, while 5 patients (4.1%) experienced recurrence. Taking into account economic factors, the patients were tolerant to pain after taking medication and did not undergo repeated PBC. Forty-six patients (38.0%) suffered from anxiety, 70 patients (57.9%) had depression, and 62 patients (51.2%) had poor sleep quality preoperatively. There were significant improvements in anxiety, depression, and sleep status postoperatively compared with preoperatively. Postoperative side effects included facial numbness in 115 patients (95.0%), masticatory muscle weakness in 86 patients (71.1%), herpes simplex in 18 patients (14.9%), and diplopia secondary to abducens nerve palsy in 2 patients (1.7%). None of the patients had corneal anesthesia, anesthesia dolorosa, aseptic meningitis, cerebrospinal fluid leakage, subarachnoid hemorrhage, carotid cavernous fistula, or death in this study. LIMITATIONS: This study was a single-center retrospective study, the sample size was small, and the follow-up time was relatively short. Therefore, the long-term efficacy of PBC for postoperative recurrent TN needs further evaluation from multiple centers with a large sample size and long-term follow-up. CONCLUSIONS: PBC is a minimally invasive, safe, and effective procedure. Moreover, it significantly improves the symptoms of anxiety, depression, and sleep quality caused by TN, so it appears to be regarded as an optimized choice for patients with recurrent TN after surgical procedures.