Macroautophagy/autophagy plays a crucial role in maintaining nervous system homeostasis but its role in chronic postoperative pain (CPOP) remains poorly understood. Here, we identify impaired autophagy and the accumulation of synaptic proteins in the anterior cingulate cortex (ACC) during the maintenance of CPOP after skin/muscle incision and retraction (SMIR). Lysosomal hydrolase levels are reduced upon SMIR, accompanied by a deficiency of the lysosomal trafficking protein transmembrane protein 251 (TMEM251, also named LYSET). TMEM251 overexpression alleviates impaired autophagy, accumulation of synaptic proteins within autophagy substrates, and maintenance of CPOP in SMIR mice. Conversely, TMEM251 knockdown induces autophagy impairment, accumulation of synaptic proteins, and chronic pain phenotypes in naive mice. Autophagy dysfunction is most pronounced in CaMKIIα-positive neurons in the ACC post-surgery, resulting in their activation, which is mitigated by TMEM251 overexpression. Chemogenetic activation of CaMKIIα neurons exacerbates autophagy impairment and CPOP, while their inhibition rescues SMIR-induced autophagy and pain phenotypes. Taken together, our study highlights the close relationship between impaired autophagy and neuronal activation in the promotion of chronic postoperative pain.

Sleep deprivation (SD) is a growing public health concern with implications for pain sensitivity and well-being. Although the relationship between sleep and pain is well understood, the underlying mechanisms remain largely unknown. This study investigates how SD influences pain sensitivity by modulating gene expression in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of mice. Using the CPW sleep deprivation model, mice were deprived of sleep for three days, simulating preoperative conditions. Behavioral tests revealed heightened mechanical and thermal hypersensitivity post-SD. Brain MRI, immunofluorescence, and RNA sequencing analyses showed significant changes in the expression of non-coding RNAs (ncRNAs) and mRNAs in NAc and VTA, implicating several pain-related genes. Functional enrichment analysis highlighted pathways associated with neurotransmission, inflammation, and stress response. The study identified Hcrt and Apoe as critical modulators of SD-induced hyperalgesia, with potential therapeutic implications for managing pain associated with SD. Findings suggest that overlapping pathways exist between sleep and pain sensitivity, offering insights into the molecular mechanisms that connect sleep disorders with heightened pain responses.

Chronic postoperative pain (CPOP) remains a significant clinical challenge, with central sensitization being an important mechanism. However, the neuronal circuit-mediated mechanisms associated with this disorder are poorly understood. Here, we identified the nucleus accumbens core (AcbC) received excitatory projections from calcium/calmodulin-dependent protein kinase II (CaMKII)-positive neurons in the anterior cingulate cortex (ACC), playing an important role in the development of CPOP. We demonstrated that the AcbC neurons displayed the enhanced responses to both non-nociceptive and nociceptive stimuli following skin/muscle incision and retraction. Furthermore, fiber photometry and electrophysiological recordings confirmed that the activity of the ACCCaMKII-AcbC pathway was also elevated after surgery. Inhibition of AcbC neurons or the ACCCaMKII-AcbC pathway alleviated pain hypersensitivity in CPOP mice, whereas their activation induced pain phenotypes in naive mice. These findings reveal critical roles for the AcbC neurons and ACCCaMKII-AcbC pathway in CPOP pathogenesis, offering potential therapeutic targets for postoperative pain management.

Correction for 'Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway' by Qian Bai et al., J. Mater. Chem. B, 2023, https://doi.org/10.1039/d3tb00929g.

Chronic temporomandibular joint (TMJ) pain profoundly affects patients' quality of life. Trigeminal tumor necrosis factor-α (TNFα) plays a pivotal role in mediating TMJ pain in mice, yet the underlying epigenetic mechanisms remain enigmatic. To unravel these epigenetic intricacies, we employed a multifaceted approach. Hydroxymethylated DNA immunoprecipitation (hMeDIP) and chromatin immunoprecipitation (ChIP) followed by qPCR were employed to investigate the demethylation of TNFα gene (Tnfa) and its regulation by ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in a chronic TMJ pain mouse model. The global levels of 5-hydroxymethylcytosine (5hmc) and percentage of 5hmc at the Tnfa promoter region were measured in the trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) following complete Freund's adjuvant (CFA) or saline treatment. TET1 knockdown and pain behavioral testing were conducted to ascertain the role of TET1-mediated epigenetic regulation of TNFα in the pathogenesis of chronic TMJ pain. Our finding revealed an increase in 5hmc at the Tnfa promoter region in both TG and Sp5C of CFA-treated mice. TET1 was upregulated in the mouse TG, and the ChIP result showed TET1 direct binding to the Tnfa promoter, with higher efficiency in the CFA-treated group. Immunofluorescence revealed the predominant expression of TET1 in trigeminal neurons. TET1 knockdown in the TG significantly reversed CFA-induced TNFα upregulation and alleviated chronic TMJ pain. In conclusion, our study implicates TET1 as a vital epigenetic regulator contributing to chronic inflammatory TMJ pain via trigeminal TNFα signaling. Targeting TET1 holds promise for epigenetic interventions in TMJ pain management.

Sepsis is a fatal illness worldwide, particularly in the intensive care unit(ICU), and effective treatments for sepsis are currently scarce. The sedative medicine dexmedetomidine(DEX) has been found to reduce mortality in septic rats. Nevertheless, the association between DEX and mortality in septic patients remains disputed. We aimed to assess the relationship between the two. In this cohort study, We included patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC)-Ⅳ database between 2008 and 2019. The primary outcome was overall in-hospital mortality. The secondary outcomes were 30-day mortality and length of hospital stay (hospital LOS). We used multivariable Cox regression and propensity score analyses to obtain an adjusted hazard ratio (HR) with 95% confidence. A total of 22633 sepsis patients were included, of whom 51.53% were female. DEX use was associated with lower overall in-hospital mortality [12.8% vs. 15.7%,HR 0.55; P < 0.001], reduced 30-day mortality [14.1% vs. 19.7%,HR 0.51;P < 0.001], and longer hospital LOS [13.7 d vs. 7.7 d,HR 6.51; P < 0.001]. The results are consistent across sensitivity and subgroup analyses, as well as propensity score matching. DEX use may be linked to decreased risk-adjusted mortality in sepsis patients. Additional clinical research is needed to confirm and validate this connection.

Abstract Background Gastric cancer receives considerable attention not only because it is the most common cancer all through the world, but also because it’s on the top third leading reason for cancer-related death. Lidocaine is a well-documented local anesthetic that has been reported to suppress cancer development. The study explored the effects of lidocaine on the growth, migration and invasion of the gastric carcinoma cell line MKN45 and the mechanism behind. Methods The effect of lidocaine on viability, proliferation and apoptosis of MKN45 cells were analyzed by Cell Counting Kit-8 assay, BrdU staining assay and flow cytometry, respectively. Moreover, cell migration and invasion were both examined by Transwell assay. The expression of apoptosis-, migration-, and invasion-related proteins were detected by western blot. The relative expression of miR-145 was determined by qRT-PCR. Moreover, the impact which lidocaine brought on MEK/ERK and NF-κB pathways were examined by western blot. Results Lidocaine inhibited viability, proliferation, migration, and invasion of MKN45 cells, while enhanced apoptosis. Moreover, miR-145 expression was enhanced by lidocaine; and transfection with miR-145 inhibitor increased cell viability, proliferation, migration, and invasion, but inhibited apoptosis. The up-regulation of miR-145 was partly contributed to the inhibitory effect of lidocaine on gastric cancer cell line MKN45. Finally, lidocaine inactivated MEK/ERK and NF-κB pathways via up-regulation of miR-145. Conclusions Our results suggested that lidocaine decreased growth, migration and invasion of MKN45 cells via regulating miR-145 expression and further inactivation of MEK/ERK and NF-κB signaling pathways.

Background: Colon adenocarcinoma (COAD) is the most common type of colorectal cancer. Pain is a multidimensional unpleasant experience and various molecular and cellular pathways are implicated in pain signaling. Nevertheless, the exploration of pain-related genes related to colon adenocarcinoma is not clear yet. Methods: In this study, the pathways enriched for pain-related genes were analyzed by Metascape. Then, we obtained pain subtypes versus classical subtypes and explored the link between the two. Next, marker genes for different pain subtypes were identified, the enrichment pathways were explored and these marker genes were used to validate the pain subtypes. We then performed an investigation of survival differences between pain subtypes by selecting specific top pathways in each subtype, calculating top pathway scores, and calculating pathway differences by heatmap and Kruskal test. Finally, we predicted the response of different pain subtypes to immunotherapy. Results: A total of 146 pain-related genes were enrolled in this study and we finally obtained 4 painful subtypes and 4 stable subtypes. The marker genes for subtypes were validated by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and found to have a worse prognosis for CS1. The genes of CS1, CS2, CS3 and CS4 markers were mainly enriched in the pathways of Focal adhesion, Human T cell leukemia virus1 infection, Metabolic pathway, and Pertussis, respectively. CS1 and CS4 are more immunogenic. Moreover, CS1 is more sensitive to treatment with CTLA4 inhibitors, CS4 is sensitive to treatment with PD-1 inhibitors. Conclusions: Our study's identification of four pain subtypes of COAD provides new ideas for personalised therapy for patients with COAD.

Inflammatory cytokines that are secreted into the spinal trigeminal nucleus caudalis (Sp5C) may augment inflammation and cause pain associated with temporomandibular joint disorders (TMD). In a two-step process, we attached triphenylphosphonium (TPP) to the surface of a cubic liposome metal-organic framework (MOF) loaded with ruthenium (Ru) nanozyme. The design targeted mitochondria and was designated Mito-Ru MOF. This structure scavenges free radicals and reactive oxygen species (ROS) and alleviates oxidative stress. The present study aimed to investigate the effects and mechanisms by which Mito-Ru MOF ameliorates TMD pain. Intra-temporomandibular joint (TMJ) injections of complete Freund's adjuvant (CFA) induced inflammatory pain for ≥10 d in the skin areas innervated by the trigeminal nerve. Tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1), and ROS also have been proved to be significantly upregulated in the Sp5C of TMD mice. Moreover, a single Mito-Ru MOF treatment alleviated TMD pain for 3 d and downregulated TNF-α, NF-κB, lncRNA NEAT1, and ROS. NF-κB knockdown downregulated NEAT1 in the TMD mice. Hence, Mito-Ru MOF inhibited the production of ROS and alleviated CFA-induced TMD pain via the TNF-α/NF-κB/NEAT1 pathway. Therefore, Mito-Ru MOF could effectively treat the pain related to TMD and other conditions associated with severe acute inflammatory activation.

Neuropathic pain (NP) is the chronic pain in patients resulting from injuries or diseases in the somatosensory nervous system. However, effective treatment remains limited to opioids. Currently, there is an urgent need to develop new specific pharmaceuticals with low abuse potentiality. Cannabinoid receptor 2 (CB2R) is one of the significant receptors in the endocannabinoid system. It is widely expressed in the central nervous system, especially enriched in glial cells, and plays an important role in the occurrence and development of inflammation in the nervous system. CB2R activation has a neuroprotective effect on nerve injury. In this study, we report increased and more reactive microglia (with larger cell body, shorter processes, and fewer endpoints) observed in the spinal dorsal horn of spared nerve injury (SNI) rats. Continuous intrathecal administration of CB2R agonist PM226 attenuated mechanical and cold hyperalgesia in rats and prevented the transition of microglia to the proinflammatory stage. Thus, microglia transitioned into the neuroprotective stage. Meanwhile, the proinflammatory factors TNF-α and iNOS decreased, and the levels of anti-inflammatory factors Arg-1 and IL-10 increased. The content of P2X7 receptors in the spinal dorsal horn of rats increases with time after SNI. After continuous intrathecal administration of PM226, the content of P2X7 protein decreases significantly. The administration of P2X7 inhibitor A-438079 alleviated the mechanical hyperalgesia of rats, reduced the number of microglia, and decreased the content of P2X7. These results indicate that P2X7 is involved in the neuroprotective effect caused by CB2R activation. In conclusion, this study provides new insights into the neuroprotective mechanism of CB2R activation.

Objective:To evaluate the optimization strategy of labor analgesia in obese parturients using dural puncture epidural (DPE) combined with programmed intermittent epidural bolus (PIEB).Methods:Eighty American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ obese primiparae, who were at full term with a singleton fetus in vertex presentation, aged 20-40 yr, with body mass index of 30-40 kg/m 2, at 37-42 week gestation, with cervical dilation of 2-5 cm, and with visual analogue scale score ≥50 mm, were divided into 2 groups ( n=40 each) using a random number table method: DPE plus PIEB group (DPEP group) and DPE plus continuous epidural infusion group (DPEC group). All parturients received DPE labor analgesia, and parturients received PIEB (DPEP group) and continuous epidural infusion (DPEC group) to maintain analgesia during labor. In DPEP group, the patient-controlled epidural analgesia pump was set up to deliver a 5 ml bolus dose with a 20-min lockout interval and background infusion at 2 ml/12 min after an initial dose of 8 ml. In DPEC group, the patient-controlled epidural analgesia pump was set up to deliver a 5 ml bolus dose with a 20-min lockout interval and background infusion at 10 ml/h after an initial dose of 8 ml. The analgesia solution contained 0.1% ropivacaine plus 0.3 μg/ml sufentanil. The time to achieve adequate analgesia, consumption of ropivacaine per unit time, height of sensory block at the thoracic vertebral level, modified Bromage score, effective pressing times of patient-controlled analgesia, the number of rescue analgesia, Apgar score, delivery mode, occurrence of adverse reactions and maternal satisfaction with labor analgesia were recorded. Results:Compared with DPEC group, the time to achieve adequate analgesia was significantly shortened, the consumption of ropivacaine per unit time was decreased, and the number of rescue analgesia and effective pressing times of patient-controlled analgesia were decreased in DPEP group ( P<0.05). There were no significant differences in the height of sensory block at the thoracic vertebral level, modified Bromage score, Apgar score, delivery mode, incidence of adverse reactions and maternal satisfaction with labor analgesia between the two groups ( P>0.05). Conclusions:DPE combined with PIEB offers faster onset and better effect and achieves a greater local anesthetics-sparing effect when used for labor analgesia in obese parturients.

OBJECTIVE:The optimal time to start renal replacement therapy (RRT) for acute kidney injury (AKI) remains controversial. We aim to compare the effects of early vs. delayed RRT initiation on clinical outcomes in adult patients with AKI.MATERIALS AND METHODS:PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, ClinicalTrials.gov, and the International Clinical Trial registry platform were systematically searched from inception to 7 August 2022. The review included randomized clinical trials (RCTs) comparing early and delayed initiation of RRT in AKI patients. The selected primary outcomes were short-term and long-term mortality. Secondary outcomes included RRT dependency, intensive care unit (ICU) length of stay, hospital length of stay, mechanical ventilator-free days, vasoactive agents-free days, RRT-free days, and adverse events.RESULTS:Overall, 15 RCTs, including 5,625 patients, were analyzed. Early RRT showed no survival benefit when compared to the delayed therapy (28-or 30-day mortality: RR, 1.01, 95% CI: 0.94-1.08, p = 0.87; 60-day mortality: RR, 0.87, 95% CI: 0.71-1.06, p = 0.16; 90-day mortality: RR, 1.00, 95% CI: 0.88-1.13, p = 0.97; in-hospital mortality: RR, 1.05, 95% CI: 0.88-1.24, p = 0.58; ICU mortality: RR, 1.00, 95% CI: 0.91-1.10, p = 0.98). The delayed RRT did not lead to a higher risk of RRT dependency, ICU, or hospital length of stay than the early RRT. Similarly, early initiation of RRT did not lead to longer ventilator-free, vasoactive agent-free, and RRT-free days. However, early RRT initiation was associated with more adverse events.CONCLUSIONS:Our study suggested that early RRT initiation was not associated with survival benefits or better clinical outcomes and increased the risk of RRT-associated adverse events. Current evidence does not support the use of early RRT for AKI patients without urgent indications.

Trigeminal neuropathic pain (TNP) induces mechanical allodynia and hyperalgesia, which are known to alter gene expression in injured dorsal root ganglia primary sensory neurons. Non-coding RNAs (ncRNAs) have been linked to TNP. However, the functional mechanism underlying TNP and the expression profile of ncRNAs in the trigeminal ganglion (TG) and trigeminal subnucleus caudalis (Sp5C) are still unknown. We used RNA sequencing and bioinformatics analysis to examine the TG and Sp5C transcriptomes after infraorbital nerve chronic constrictive injury (IoN-CCI). The robust changes in the gene expression of lncRNAs, circRNAs, and mRNAs were observed within the TG and Sp5C from mice that underwent IoN-CCI and the sham-operated mice (day 7). In total, 111,003 lncRNAs were found in TG and 107,157 in Sp5C; 369 lncRNAs were differentially expressed in TG, and 279 lncRNAs were differentially expressed in Sp5C. In addition, 13,216 circRNAs in TG and 21,658 circRNAs in Sp5C were identified, with 1,155 circRNAs and 2,097 circRNAs differentially expressed in TG and Sp5C, respectively. Furthermore, 5,205 DE mRNAs in TG and 3,934 DE mRNAs in Sp5C were differentially expressed between IoN-CCI and sham groups. The study revealed a high correlation of pain-related differentially expressed genes in the TG and Sp5C to anxiety, depression, inflammation, neuroinflammation, and apoptosis. Gene Ontology analysis revealed that binding-related molecular functions and membrane-related cell components were significantly enriched. Kyoto Encyclopedia of Genes and Genomes analysis shows the most significant enrichments in neurogenesis, nervous system development, neuron differentiation, adrenergic signaling, cAMP signaling, MAPK signaling, and PI3K-Akt signaling pathways. Furthermore, protein-protein interaction analysis showed that hub genes were implicated in neuropeptide signaling pathways. Functional analysis of DE ncRNA-targeting genes was mostly enriched with nociception-related signaling pathways underpinning TNP. Our findings suggest that ncRNAs are involved in TNP development and open new avenues for research and treatment.

Abstract Morphine tolerance is one of the current challenging issues in the treatment of chronic pain. Recent studies have shown that ROS derived by NADPH oxidase (NOX) and endoplasmic reticulum (ER) stress is participated in the development of morphine tolerance. However, which NOX subtype initiates the ER stress during the development of morphine tolerance is not fully clear. NOX4 mainly expressed at intracellular membranes, such as ER and mitochondria, which sole function is to produce ROS as the major product. At present, whether NOX4 is activated and the mechanisms between NOX4 and ER stress during the development of morphine tolerance still need to be confirmed. Here, our research, for the first time, demonstrated that chronic administration of morphine up-regulated the expression of NOX4 at spinal cord through activating the three ER stress sensors (PERK, IRE1, ATF6), and subsequently leading to the activation of LC3B and P62 (a well-known autophagy marker) in GABAergic neurons. Therefore, our results may suggest that regulating NOX4 and the key factor of ER stress or autophagy may be a promising strategy to treat and prevent the development of morphine tolerance.

Morphine tolerance (MT) is currently a challenging issue related to intractable pain treatment. Studies have shown that reactive oxygen species (ROSs) derived from NADPH oxidase (NOX) and produced in response to endoplasmic reticulum (ER) stress participate in MT development. However, which NOX subtype initiates ER stress during MT development is unclear. NOX4 is mainly expressed on intracellular membranes, such as the ER and mitochondrial membranes, and its sole function is to produce ROS. Whether NOX4 is activated during MT development and the mechanisms underlying the association between NOX4 and ER stress during this process still need to be confirmed. In our study, we used the classic morphine-tolerant rat model and evaluated the analgesic effect of intrathecally injected morphine through a hot water tail-flick assay. Our research demonstrated for the first time that chronic morphine administration upregulates NOX4 expression in the spinal cord by activating three ER stress sensors, protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6), subsequently leading to the activation of microtubule-associated protein 1 light chain 3 b (LC3B) and P62 (a well-known autophagy marker) in GABAergic neurons. Our results may suggest that regulating NOX4 and the key mechanism underlying ER stress or autophagy may be a promising strategy to treat and prevent MT development.

Neuropathic pain (NP) is an intractable pain that results from primary nervous system injury and dysfunction. Herein, we demonstrated in animal models that peripheral nerve injury induced enhanced pain perception and anxiety-like behaviors. According to previous reports, nucleus accumbens (NAc) shell is required for complete expression of neuropathic pain behaviors and mood alternations, we found the elevated mRNA and protein level of Prokineticin-2 (Prok2) in the NAc shell after Chronic Constriction Injury (CCI). Prok2 knockdown in the NAc shell reversed NP and anxiety-like behaviors in rats, indicating that Prok2 might play a fundamental role in NP and anxiety co-morbidity. CCI significantly enhanced Prok2 co-expression with NF-κB P-p65 in comparison with control animals. In addition to reversing the established nociceptive hypersensitivities and anxiety simultaneously, NAc microinjection of NF-κB siRNA or specific inhibitor PDTC reversed Prok2 upregulation. Besides, Prok2 was significantly decreased in vitro when co-transfected with si-NF-κB. Dual-Luciferase assay showed NF-κB directly activated Prok2 gene transcriptional activity. Overall, these findings provide new insights into the neurobiological mechanisms behind NP and comorbid anxiety. The NF-κB/Prok2 pathway could be a potential therapeutic target for NP and anxiety disorders.

目的 评价甲苯磺酸瑞马唑仑与丙泊酚用于老年无痛结肠镜检查的有效性及安全性.方法 择期拟行无痛结肠镜检查的老年40例,性别不限,年龄65～75岁,BMI 18～30 kg/m2.ASA分级为Ⅱ～Ⅲ级.采取随机数字表法分为甲苯磺酸瑞马唑仑组(R组)和丙泊酚组(P组),各20例.受检者入室后,给予芬太尼50 ug.1 min后2组分别给予甲苯磺酸瑞马唑仑5 mg、丙泊酚1.2 mg/kg.镇静评分(MOAA/S评分)<3分开始镜检.分别间断给予维持剂量甲苯磺酸瑞马唑仑1.5 mg、丙泊酚0.4 mg/kg,维持镇静评分<4分.记录维持量追加次数、诱导时间、手术时间、苏醒时间、失败例数.监测给药前(T0)、镜检即刻(T1),以及置镜后1 min(T2)、3 min(T3)、5 min(T4)时的SBP、DBP、SpO2.统计心动过缓、低血压、呼吸暂停、缺氧、注射痛、苏醒延迟,以及恶心呕吐发生例数.结果 R组诱导时间明显长于P组,差异有统计学意义(P<0.05);手术时间等其余差异均无统计学意义(P>0.05).P组患者T2、T3时点的SBP、DBP,以及T2时点的SpO2均较T0时点明显下降;R组患者T2、T3时点的SBP、DBP,以及T2时点的SpO2明显高于P组.以上差异均有统计学意义(P<0.05).R组不良事件发生率明显低于P组,差异有统计学意义(P<0.05).结论 与丙泊酚比较,甲苯磺酸瑞马唑仑复合芬太尼麻醉用于65～75岁老年人无痛结肠镜检查,麻醉效果好且安全性高.

Background: Postoperative cognitive dysfunction (POCD) affects numerous patients each year and is associated with poor outcomes. Currently, the duration of POCD is not known. This preclinical study determined whether POCD was persistent, different between sexes and transmittable to the next generation. Methods: Two-month-old Sprague-Dawley rats had left carotid artery exposure under isoflurane anesthesia and their learning and memory were assessed from 5 days, 2 months, and 4 months after surgery. Rats with or without surgery were mated when they were 4 or 6 months old, and the learning and memory of the offspring were tested at 2 months of age. Results: Males exposed to surgery took a longer time to identify the target box after training sessions in a Barnes maze and had less freezing behavior in context-related fear conditioning than control rats when the tests were started 5 days after surgery. Similarly, female rats had a poorer performance than control rats in the Barnes maze test from 5 days after surgery. However, these poorer performances were not observed when the tests were administered 2 or 4 months after surgery. The offspring of rats with surgery had a performance similar to that of the offspring of control rats. Conclusions: Our results suggest that both male and female rats develop POCD but that the learning and memory dysfunction appears to be more severe in male rats. POCD may not be persistent and does not transmit to the next generation.