Cancer-related pain and anxiety significantly negate the quality of life in patients. Oligodendrocyte precursor cells (OPCs) were reported to involve in engulf synapses and remodel neural circuits. This study aimed to elucidate the role of OPCs-mediated phagocytosis of GABAergic synapses in a mouse model of bone cancer pain. Male C3H mice were utilized to establish a model of bone cancer pain. In vivo fiber photometry was used to monitor the activity of GABAergic neurons, and chemogenetic techniques were applied to modulate neuronal excitation. The phagocytosis of GABAergic synapses by OPCs was visualized via immunofluorescence-based 3D reconstruction and immunoelectron microscopy. Interventions targeting lipocalin-2 (LCN2) and its receptor SLC22A17 were carried out with adeno-associated virus (AAV), siRNA, and pharmacological tools. On the 21st postoperative day, mice with bone cancer displayed significant pain and anxiety-like behaviors. Tumor-bearing mice exhibited a compensatory increase in calcium activity among GABAergic neurons within the anterior cingulate cortex (ACC). Compared with sham-operated mice, OPC phagocytosis of GABAergic synapses was higher in the tumor-bearing mice than controls. Concurrently, a pronounced upregulation of LCN2 expression was observed in the tumor group. Administration of LCN2-neutralizing antibodies or AAV-mediated intervention markedly alleviated pain and anxiety-related behaviors in mice with bone cancer. Moreover, the LCN2 receptor SLC22A17 expression was significantly increased. Targeted inhibition of SLC22A17 induced cytoskeletal remodeling and decreased their phagocytic capacity of OPCs. Collectively, LCN2/SLC22A17 signal was involved in OPCs-mediated phagocytosis of GABAergic synapses and contributed to cancer pain and anxiety development.

Cancer pain, a frequent complication in patients with cancer, adversely affects quality of life and survival rates. Microglia promote nociceptive information transmission by modulating myelin integrity during pain perception. However, the specific mechanisms by which microglia regulate myelin in the context of cancer pain remain poorly understood. In this study, we developed a bone cancer pain model to examine the interactions among microglia, myelin, and oligodendrocyte precursor cells and their roles in cancer pain. Our study found that mice with bone cancer pain had oligodendrocyte differentiation defects and myelin loss, and that promoting myelination did not relieve pain. In addition, we observed that reactive microglia and inflammatory cytokines increased and microglia phagocytosed myelin in mice with bone cancer pain. Inhibition of microglia not only alleviated pain behaviors in mice with bone cancer but also mitigated myelin phagocytosis and the proliferation of oligodendrocyte precursor cells. Our study suggests that microglia-mediated myelin loss and oligodendrocyte precursor cell proliferation may be one of the pathological mechanisms underlying pain in mice with bone cancer.

Persistent postoperative pain (PPP) is associated with neuroinflammation and excitatory/inhibitory(E/I) imbalance in the spinal cord. Notably, trained immunity enhances the immune reactivity of microglia to secondary stimuli, exacerbating neuroinflammation and synaptic engulfment of microglia. Here, we investigated whether preoperative anxiety stress promotes trained immunity in microglia and how this phenomenon influences microglia-mediated synaptic engulfment. Given the role of glycolysis in trained immunity, we focused on microglial glucose metabolism. Rutin inhibits microglial glycolysis and reduces neuroinflammation, prompting further investigation into its therapeutic potential for PPP. Preoperative anxiety was modeled in male Sprague-Dawley (SD) rats using single prolonged stress (SPS). We found that SPS aggravated and prolonged incision pain in SD rats. Mechanistically, SPS promoted trained immunity in microglia via mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling. This amplified inflammatory responses to surgical stimuli and enhanced microglial engulfment of inhibitory synapses. Rutin inhibited microglial activation and inhibitory synaptic engulfment via mTOR/HIF-1α signaling, relieving SPS-induced PPP. These findings suggest preoperative anxiety induces trained immunity in microglia, amplifying neuroinflammation and E/I imbalance in the spinal cord after surgery. Rutin attenuates this process by suppressing mTOR/HIF-1α-driven glycolysis, thereby alleviating PPP.

Sepsis-induced coagulopathy (SIC) is an early-stage coagulation disorder associated with increased morbidity and mortality in sepsis. It reflects a dysregulated host response and is considered a precursor to disseminated intravascular coagulation and multi-organ failure. Currently, there is no specific treatment for SIC beyond supportive care. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that has shown potential in regulating inflammation and coagulation pathways. This study aims to evaluate the efficacy and safety of taVNS in improving coagulation dysfunction in patients with SIC, with the primary outcome being the proportion of patients achieving a ≥2-point improvement in SIC score by day 7. This is a single-centre, randomised, sham-controlled, single-blind clinical trial designed to evaluate the efficacy of taVNS in patients with SIC. This study will enrol 184 adult patients who meet the diagnostic criteria for SIC. Participants will be randomly assigned in a 1:1 ratio to receive either active taVNS or sham stimulation for 7 consecutive days. The intervention will be applied twice daily for 7 consecutive days using standardised stimulation parameters (25 Hz, 3 mA, 60 min/session). The primary outcome is the proportion of patients achieving an improvement of ≥2 points in SIC score from baseline to day 7. Secondary outcomes include platelet count, international normalised ratio, activated partial thromboplastin time, D-dimer, fibrinogen, procalcitonin, C-reactive protein, interleukin-6, angiopoietin-2, systemic immune-inflammation index, lactic acid, duration of antibiotic therapy, length of hospital stay and 28-day all-cause mortality. Adverse events and protocol adherence will also be recorded. Data will be analysed using intention-to-treat principles. Between-group comparisons for the primary outcome will be performed using X2 tests. Repeated measures analysis of variance will be used for longitudinal secondary outcomes. The study protocol has been approved by the Ethics Committee of Yancheng Third People's Hospital (approval No. 2023-058-01). The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2400082378). Findings will be disseminated through peer-reviewed publications and academic conferences. ChiCTR2400082378.

IntroductionProne positioning with head rotation can influence cerebral haemodynamics, potentially affecting cerebral perfusion and oxygenation. Elderly patients with impaired brain perfusion and oxygenation are at an increased risk of developing postoperative delirium (POD). Despite this, few studies have explored whether head orientation during prone positioning contributes to POD in older adults, an aspect often overlooked by clinicians. This study aimed to evaluate the impact of head orientation during prone positioning on the incidence of POD in elderly patients undergoing thoracolumbar spine surgery.Methods and analysisThis study is a single-centre, randomised, single-blind trial, with the assessors blinded to the intraoperative head position. Eligible participants are patients aged ≥65 years undergoing elective thoracolumbar spine surgery. A total of 500 patients will be randomly assigned to either the prone position with the head centred, or the prone position with the head deviated. The primary outcome is the incidence of POD, measured using the 3 min Diagnostic Interview for Confusion Assessment Method (3D-CAM) until postoperative day 5. Secondary outcomes include the severity of POD assessed by the Memorial Delirium Assessment Scale (MDAS), postoperative cognitive impairment evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), intraoperative regional cerebral oxygen saturation (rSO2), changes in vertebrobasilar artery and middle cerebral artery haemodynamics, and plasma levels of calcium channel-binding protein S100 subunit beta (S100B) and neuron-specific enolase (NSE).Ethics and disseminationEthical approval was obtained from Yancheng No. 1 People’s Hospital Ethics Examination Committee (2023-K-120–01). The findings will be disseminated through presentations at annual conferences and publications in scientific journals.Trial registration numberChiCTR2300078839.

Preoperative stress has been recognized as an independent risk factor for chronic postsurgical pain (CPSP). However, the underlying mechanisms of CPSP influenced by preoperative stress remain elusive. Previous studies indicated that excessive stress could induce disruption of the blood-spinal cord barrier (BSCB). We wondered whether and how BSCB involves in CPSP by using a single prolonged stress (SPS) combining plantar incision model in male rats to mimic preoperative stress-related postsurgical pain. Here, we observed that preoperative SPS-exposed rats exhibited relentless incisional pain, which was accompanied by impairment of BSCB and persistent elevation of serum IL-6. Intraperitoneal injections of Tocilizumab (an IL-6 receptor monoclonal antibody) not only mitigated BSCB breakdown but also alleviated pain behaviors. In addition, intervening β3-adrenoceptor (ADRB3) signaling in brown adipocytes by SR59230a (a specific ADRB3 antagonist) treatment or removal of brown adipose tissues could effectively decrease serum IL-6 levels, ameliorate BSCB disruption, and alleviate incisional pain. Further results displayed that SI-exposed rats also showed markedly spinal microglia activation. And exogenous His-tagged IL-6 could pass through the disrupted BSCB, which might contribute to microglia activation. Injection of SR59230a or ablation of brown adipose tissues could effectively reduce the activation of spinal microglia. Thus, our findings suggest that serum IL-6 induced by brown adipocyte ADRB3 signaling contributed to BSCB disruption and spinal microglia activation, which might be involved in preoperative stress mediated CPSP. This work indicates a promising treatment strategy for preoperative stress induced CPSP by blocking ADRB3.

During adolescence, a second period of central nervous system (CNS) plasticity that follows the fetal period, which involves sleep deprivation (SD), becomes apparent. SD during adolescence may result in abnormal development of neural circuits, causing imbalance in neuronal excitation and inhibition, which not only results in pain, but increases the chances of developing emotion disorders in adulthood, such as anxiety and depression. The quantity of surgeries during adolescence is also consistently on the rise, yet the impact and underlying mechanism of preoperative SD on postoperative pain remain unexplored. This study demonstrates that preoperative SD induces upregulation of the P2Y 12 receptor, which is exclusively expressed on spinal microglia, and phosphorylation of its downstream signaling pathway p38Mitogen-activated protein/Nuclear transcription factor-κB (p38MAPK/NF-κB)in spinal microglia, thereby promoting microglia activation and microglial transformation into the proinflammatory M1 phenotype, resulting in increased expression of proinflammatory cytokines that exacerbate persisting postoperative incisional pain in adolescent mice. Both intrathecal minocycline (a microglia activation inhibitor) and MRS2395 (a P2Y 12 receptor blocker) effectively suppressed microglial activation and proinflammatory cytokine expression. Interestingly, supplementation with dehydrocorydaline (DHC), an extract of Rhizoma Corydalis , inhibited the P2Y 12 /p38MAPK/NF-κB signaling pathway, microglia activation, and expression of pro-inflammatory cytokines in the model mice. Taken together, the results indicate that the P2Y 12 receptor and microglial activation are important factors in persistent postoperative pain caused by preoperative SD in adolescent mice and that DHC has analgesic effects by acting on these targets. Keywords dehydrocorydaline , incisional pain , inflammation , microglia , P2Y , receptor , sleep deprivation

Chronic pain patients are often accompanied with anxiety disorder, which promote the development of each other's disease process to a certain extent and seriously affect the quality of life of patients.However, the mechanism regulating the comorbidity between the two has not been clarified.Synaptic remodeling is the alteration of synaptic structure and function, which affects the transmission of signals between neurons.Synaptic remodeling is a hot topic in the field of chronic pain and anxiety disorders, but only few studies have explored its pathological changes in chronic pain and anxiety disorders.By summarizing the relevant researches in recent years, the occurrence of chronic pain co-anxiety disorder is closely related to changes in synaptic structure, synaptic transmission efficiency and synaptic function in brain regions.Synaptic remodeling could lead to the decline of centra pain regulation ability and aggravate the progression of chronic pain accompanied by anxiety disorder through ionic amino acid receptors, neuronal transmission and interactions between neurons and glial cells.Understanding the latest research progress of the co-morbidity mechanism of chronic pain and anxiety disorder is helpful to provide theoretical basis and potential new targets for its treatment.

During adolescence, a second period of central nervous system (CNS) plasticity that follows the fetal period, which involves sleep deprivation (SD), becomes apparent. SD during adolescence may result in abnormal development of neural circuits, causing imbalance in neuronal excitation and inhibition, which not only results in pain, but increases the chances of developing emotion disorders in adulthood, such as anxiety and depression. The quantity of surgeries during adolescence is also consistently on the rise, yet the impact and underlying mechanism of preoperative SD on postoperative pain remain unexplored. This study demonstrates that preoperative SD induces upregulation of the P2Y12 receptor, which is exclusively expressed on spinal microglia, and phosphorylation of its downstream signaling pathway p38Mitogen-activated protein/Nuclear transcription factor-κB (p38MAPK/NF-κB)in spinal microglia, thereby promoting microglia activation and microglial transformation into the proinflammatory M1 phenotype, resulting in increased expression of proinflammatory cytokines that exacerbate persisting postoperative incisional pain in adolescent mice. Both intrathecal minocycline (a microglia activation inhibitor) and MRS2395 (a P2Y12 receptor blocker) effectively suppressed microglial activation and proinflammatory cytokine expression. Interestingly, supplementation with dehydrocorydaline (DHC), an extract of Rhizoma Corydalis, inhibited the P2Y12/p38MAPK/NF-κB signaling pathway, microglia activation, and expression of pro-inflammatory cytokines in the model mice. Taken together, the results indicate that the P2Y12 receptor and microglial activation are important factors in persistent postoperative pain caused by preoperative SD in adolescent mice and that DHC has analgesic effects by acting on these targets.

Patients awaiting surgical procedures often experience obvious anxiety due to discomfort and uncertain events, which is one of the most common clinical manifestations in perioperative patients. Numerous studies have confirmed that preoperative anxiety is closely related to the occurrence of postoperative adverse events, such as insomnia, pain, nausea and vomiting and neurocognitive dysfunction. Appropriate intervention or treatment for preoperative anxiety may contribute to reducing the incidence of postoperative adverse events. Although people have long known about the negative effects of preoperative anxiety and have taken certain measures, the underlying mechanism has yet to be fully elucidated. In this paper, we focus on several typical postoperative adverse events that are, particularly concerning to anesthesiologists, review their relationships with preoperative anxiety, describe the intervention strategies and provide a certain summary and outlook.

Electroacupuncture has an effective analgesia on chronic pain caused by lumbar disc herniation (LDH) clinically, however, the underlying mechanism is unclear. In this study, we investigated whether electroacupuncture alleviated pain in LDH model rats by inducing spinal microglia M2 polarization. We established a noncompression LDH rat model by implanting autologous caudal nucleus pulposus into L5/L6 nerve root. Electroacupuncture (30 min/day) treatment on the ipsilateral side was started on the 8th postoperative day, once a day for consecutive 7 days. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested for pain behavior. Western blotting was used to detect the protein expression in lumbar enlargement (L5/L6). Immunofluorescence was used to detect iNOS+/Iba-1+ and Arg-1+/Iba-1+ and CB2R+/Iba-1+ in lumbar enlargement (L5/L6). We show that PWT and PWL decreased in the LDH group while Iba-1, iNOS, and TNF-α expression increased significantly in lumbar spinal dorsal horn (SDH) after LDH surgery, and revealing that microglia were activated and polarized towards proinflammatory M1 phenotype. Electroacupuncture treatment significantly increased PWT and PWL while reducing Iba-1, iNOS, and TNF-α expression, interestingly, Arg-1 and IL-10 expression were significantly increased. Moreover, electroacupuncture treatment led to CB2 receptors on microglia upregulation, while NF-κB and p-NF-κB expression in lumbar SDH downregulation. Our study indicated that electroacupuncture may reduce nociceptive hyperalgesia by inhibiting microglia activation and microglia M1 polarization and promoting microglia M2 polarization in lumbar SDH of LDH rats, which may be caused by the activation of CB2 receptors on microglia and inhibition of NF-κB pathway in lumbar SDH.

During adolescence, a second period of central nervous system (CNS) plasticity that follows the fetal period, which involves sleep deprivation (SD), becomes apparent. SD during adolescence may result in abnormal development of neural circuits, causing imbalance in neuronal excitation and inhibition, which not only results in pain, but increases the chances of developing emotion disorders in adulthood, such as anxiety and depression. The quantity of surgeries during adolescence is also consistently on the rise, yet the impact and underlying mechanism of preoperative SD on postoperative pain remain unexplored. This study demonstrates that preoperative SD induces upregulation of the P2Y 12 receptor, which is exclusively expressed on spinal microglia, and phosphorylation of its downstream signaling pathway p38Mitogen-activated protein/Nuclear transcription factor-κB (p38MAPK/NF-κB)in spinal microglia, thereby promoting microglia activation and microglial transformation into the proinflammatory M1 phenotype, resulting in increased expression of proinflammatory cytokines that exacerbate persisting postoperative incisional pain in adolescent mice. Both intrathecal minocycline (a microglia activation inhibitor) and MRS2395 (a P2Y 12 receptor blocker) effectively suppressed microglial activation and proinflammatory cytokine expression. Interestingly, supplementation with dehydrocorydaline (DHC), an extract of Rhizoma Corydalis , inhibited the P2Y 12 /p38MAPK/NF-κB signaling pathway, microglia activation, and expression of pro-inflammatory cytokines in the model mice. Taken together, the results indicate that the P2Y 12 receptor and microglial activation are important factors in persistent postoperative pain caused by preoperative SD in adolescent mice and that DHC has analgesic effects by acting on these targets.

Recent studies have shown that fatty acid binding protein (FABP) not only participates in lipid metabolism, but also has many other biological functions, including regulating the generation and development of pain. The mechanism of FABP regulating pain is very complex. The structure and function of FABP, its influence on pain and underlying mechanism, as well as the application and effect of FABP inhibitors are summarized here. Different subtypes of FABP have different structures and different mechanisms for pain regulating. They mainly activate pain-related receptors, regulate the metabolism of cannabinoid and other pain-related molecules, affect inflammatory signaling pathways, and then affect the generation and development of pain. The inhibition of FABP has also become a new target for the development of analgesic drugs. FABP inhibitors emerged and achieved certain analgesic effects in animal models, providing a new direction for the development of potential analgesic targets.

BACKGROUND:Dysfunction of the blood-spinal cord barrier (BSCB) contributes to the occurrence and development of neuropathic pain (NP). Previous studies revealed that the activation of cyclophilin A (CypA)-metalloproteinase-9 (MMP9) signaling pathway can disrupt the integrity of the blood-brain barrier (BBB) and aggravate neuroinflammatory responses. However, the roles of CypA-MMP9 signaling pathway on BSCB in NP have not been studied. This study aimed to investigate the effect of CypA on the structure and function of the BSCB and pain behaviors in mice with NP. METHODS:We first created the mouse chronic constriction injury (CCI) model, and they were then intraperitoneally injected with the CypA inhibitor cyclosporine A (CsA) or vehicle. Pain behaviors, the structure and function of the BSCB, the involvement of the CypA-MMP9 signaling pathway, microglia activation, and expression levels of proinflammatory factors in mice were examined. RESULTS:CCI mice presented mechanical allodynia and thermal hyperalgesia, impaired permeability of the BSCB, downregulated tight junction proteins, activated CypA-MMP9 signaling pathway, microglia activation, and upregulated proinflammatory factors, which were significantly alleviated by inhibition of CypA. CONCLUSIONS:Collectively, the CypA-MMP9 signaling pathway is responsible for CCI-induced NP in mice by impairing the structure and function of the BSCB, and activating microglia and inflammatory responses.

Post-traumatic stress disorder (PTSD)-associated cognitive dysfunction significantly disturbs patients' quality of life and will to live. However, its underlying mechanism is as yet unknown. Recent researches indicate that blood-brain barrier (BBB) breakdown is responsible for early cognitive dysfunction. Microglia might participate in remodeling of BBB-associated tight junction and regulating BBB integrity. Nevertheless, it is unclear whether microglia activation and BBB injury involve in PTSD-associated cognitive dysfunction. Hence, we established an animal model of PTSD, single prolonged stress (SPS), and investigated permeability changes in the hippocampus and further explored the effects of microglia on BBB remodeling. The Y maze was used to assess the changes of cognitive function. The sodium fluorescein (NaFlu) assay and western blotting analysis were employed to detect BBB integrity changes. Minocycline was administered to inhibit microglial activation. Immunofluorescence stains were used to assess the activation states in microglia. The results showed that SPS-exposed rats exhibited poorer cognitive performance, higher passage of NaFlu, and lower expression of tight junction proteins (occludin and claudin 5) in the hippocampus on the day after SPS, but no difference on the 7th day. Inhibition of microglial activation by minocycline attenuated poor cognitive performance and BBB impairment including the extravasation of NaFlu and protein levels of the tight junction. Taken together, the present study indicates that BBB impairment may underlie the shared pathological basis of PTSD and cognitive dysfunction. Microglial activation may involve in BBB remodeling at the early stage of SPS.

Prolongation of postsurgical pain caused by pre-operative stress is a clinically significant problem, although the mechanisms are not fully understood. Stress can promote the pro-inflammatory activation of microglia, and the transcription factor CCAAT/enhancer-binding protein (C/EBP) β regulates pro-inflammatory gene expression in microglia. Therefore, we speculated that C/EBPβ in spinal microglia may have critical roles in the development of chronic postsurgical pain. Accordingly, in this study, we used a single prolonged stress (SPS) procedure and plantar incisions to evaluate the roles of C/EBPβ in postsurgical pain. Our experiments showed that SPS exposure prolonged mechanical allodynia, increased the expression of C/EBPβ and pro-inflammatory cytokines, and potentiated the activation of spinal microglia. Subsequently, microinjection of C/EBPβ siRNA attenuated the duration of SPS-prolonged postoperative mechanical allodynia and inhibited microglial activation in the spinal cord. Conversely, mimicking this increase in C/EBPβ promoted microglial activation via pretreatment with a pre-injection of AAV5-C/EBPβ, leading to prolongation of postsurgical pain. Overall, these results suggested that spinal microglia may play key roles in prolongation of postsurgical pain induced by pre-operative stress and that C/EBPβ may be a potential target for disease treatment.

目的 探讨行下肢骨折手术的老年患者术后2年内死亡的预测因素.方法 收集择期行下肢骨折手术的老年患者(年龄≥65岁)的临床资料,根据术后2年内的生存状况,将患者分为生存组和死亡组.对两组间差异有统计学意义的因素进行多因素Cox回归分析,筛选出2年内死亡的预测因素,再通过受试者工作特征曲线(receiver operation characteristic,ROC)及曲线下面积(area under the curve,AUC)评估其预测能力.结果 最终纳入372例患者资料进行统计分析,其中2年内死亡55例(病死率为14.7％).Cox回归分析结果显示,年龄≥75岁(HR:2.155,95％CI:1.093～4.247)、美国麻醉医师协会(American Society of Anesthesiologists,ASA)分级≥3级(HR:2.978,95％CI:1.242～7.183)、Charlson 合并症指数(Charlson Comorbidity Index,CCI)评分≥2(HR:4.649,95％CI:2.467～8.761)、术前贫血(HR:2.050,95％CI:1.066～3.943)及术后住院期间发生心脑血管事件(HR:3.026,95％CI:1.491～6.140)为该类患者术后2年内死亡的预测因素,其AUC分别为0.677、0.733、0.700、0.584和0.658.上述5种因素联合预测的AUC为0.858,显著高于任意单一因素;ASA分级≥3级的预测敏感度最高(敏感度87.3％);CCI评分≥2的预测特异度最强(特异度92.7％).结论 老年患者行下肢骨折手术后2年内死亡的预测因素为年龄≥75岁、ASA分级≥3级、CCI评分≥2、术前贫血和术后住院期间发生心脑血管事件,且5种因素联合预测具有更高的预测价值,提示有针对性的进行围术期干预可能有助于提高患者长期生存率.

术前焦虑是围术期患者最常见的临床问题之一.许多研究表明,术前焦虑与围术期不良事件的发生密切相关,如失眠、术后疼痛、术后恶心呕吐、术后谵妄等.术前焦虑与围术期不良事件发生机制的关联目前尚未完全清楚,可能涉及多个系统功能的调节紊乱.针对术前焦虑进行合理的干预或治疗,或将有助于减少围术期不良事件的发生.本文选择失眠、术后疼痛、术后恶心呕吐及术后谵妄等较为典型围术期不良事件,从术前焦虑与围术期不良事件的关系、发生机制及干预策略等角度予以综述.

Anxiety and depression induced by cancer-related pain disturb quality of life and willingness to survive. As a component of the limbic system, the basolateral amygdala (BLA) is critical for processing negative emotions. The reactive microglial engulfment of synapses may promote depression during adolescence. However, whether microglia phagocytose synapses to mediate cancer pain-induced depression remains unclear. The present study established a bone cancer-pain model to investigate the association between dendritic spine synapses and depressive-like behavior and explore the phagocytic function of microglia in the BLA. We found that tumor-bearing mice experienced postoperative pain-related depression, and their BLAs exhibited reactive microglia, as well as phagocytic synapses. The microglial inhibitor minocycline effectively mitigated depressive behavior, synaptic damage, and the phagocytic function of microglia. Our study implicates microglia-mediated synaptic loss in the BLA may act as the pathological basis of depressive-like behavior in bone cancer pain model.

Sleep deprivation,the process and state of partial or complete lack of normal sleep caused by various factors,is prevalent at present.Seriously impairing the physical and mental health,sleep deprivation has become a public health problem that cannot be ignored.Studies have demonstrated that blood-brain barrier impairment is the key pathophysiological process of a variety of neurological diseases.Although clinical and basic studies have suggested that sleep deprivation can induce blood-brain barrier impairment,the underlying mechanisms remain to be elucidated.This review summarizes the advances in the mechanisms of blood-brain barrier impairment induced by sleep deprivation.