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PURPOSE: Pregnancy-induced analgesia develops in late pregnancy, but its mechanisms are unclear. The anterior cingulate cortex (ACC) plays a key role in the pathogenesis of neuropathic pain. The authors hypothesized that pregnancy-induced analgesia ameliorates neuropathic pain by suppressing activation of microglia and the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and by upregulating opioid receptors in the ACC in late-pregnant mice. METHODS: Neuropathic pain was induced in non-pregnant (NP) or pregnant (P) C57BL/6JJmsSlc female mice by partial sciatic nerve ligation (PSNL). The nociceptive response was evaluated by mechanical allodynia and activation of microglia in the ACC was evaluated by immunohistochemistry. The expressions of phosphorylated AMPA receptors and opioid receptors in the ACC were evaluated by immunoblotting. RESULTS: In von Frey reflex tests, NP-PSNL-treated mice showed a lower 50% paw-withdrawal threshold than NP-Naïve mice on experimental day 9. No difference in 50% paw-withdrawal threshold was found among the NP-Naïve, NP-Sham, P-Sham, and P-PSNL-treated mice. The number of microglia in the ACC was significantly increased in NP-PSNL-treated mice compared to NP-Sham mice. Immunoblotting showed significantly increased expression of phosphorylated AMPA receptor subunit GluR1 at Ser831 in NP-PSNL-treated mice compared to NP-Sham mice. Immunoblotting also showed significantly increased δ-opioid receptor in the ACC in P-Sham and P-PSNL-treated mice compared to NP-Sham mice. CONCLUSION: Pregnancy-induced analgesia ameliorated neuropathic pain by suppressing activation of microglia and the expression of phosphorylated AMPA receptor subunit GluR1 at Ser831, and by upregulation of the δ-opioid receptor in the ACC in late-pregnant mice.

DOI： 10.1007/s00540-024-03402-9

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BACKGROUND: Neuromodulation by magnetic field through the AT-04 (ait® (AT-04); Peace of Mind Co., Ltd., Kumamoto, Japan) has improved allodynia in neuropathic pain model rats. This report focuses on neuromodulation through magnetic field exposure using the AT-04 that provided an analgesic effect in a patient with neuropathic pain. CASE PRESENTATION: A 47-year-old man presented with flaccid paralysis and extensive neuropathic pain and scored 7 on the 11-point Numerical Rating Scale (NRS) for his left upper limb. The patient was treated with neuromodulation by magnetic field exposure using the AT-04. Baseline NRS scores were obtained three times daily during the baseline period (days 1-5). Magnetic field exposure was then performed for 30 min three times daily (morning, noon, and evening) at home for 36 days, which was termed the intervention period (days 6-41). During the baseline period, the median NRS score was 7 and the baseline NRS score for calculating the percentage of nonoverlap data (PND) was 6. During the intervention period, the median NRS score was 4 and the PND value of the NRS score was 77.8% (28/36). Neuromodulation by magnetic field exposure using the AT-04 effectively decreased the patient's NRS score. The patient had no adverse effects during the intervention period. CONCLUSIONS: Neuromodulation by magnetic field exposure using the AT-04 was effective in decreasing the NRS score in a patient with neuropathic pain. The AT-04 portable magnetic field-generating device shows potential as a therapeutic option for refractory neuropathic pain.

DOI： 10.1186/s40981-024-00694-4

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BACKGROUND AND OBJECTIVES: There is still no consensus on the analgesic range and mechanisms of action of modified thoracoabdominal nerve block through perichondrial approach (M-TAPA). This cadaveric study aimed to determine the spread of an injectate following simulated M-TAPA. METHODS: Simulated M-TAPA injections (n=8) were administered on both sides of soft embalmed Thiel cadavers with 25 mL of a saline-soluble dye. Anatomic dissection was performed to document staining (deeply, faintly, or not stained) of the anterior cutaneous branches of the thoracoabdominal nerves and determine the extent of the injectate spread of the dye to the intercostal space in the thoracic cage following a simulated M-TAPA. RESULTS: The median (IQR) dermatome of the stained segmental nerve was T10 (T8-T11) and the median (IQR) number of stained segmental nerves was 3 (4-2). The T9, T10 and T11 segmental nerves were stained in 75%, 100% and 62.5% of simulated M-TAPA, respectively. Conversely, the T8 segmental nerve was stained in only 25% of simulated M-TAPA. No injectate spread of dye to the intercostal space in the thoracic cage was observed in eight simulated injections of M-TAPA. CONCLUSION: Our findings suggest that M-TAPA most likely involves the T9, T10 and T11 segmental nerves and that the local anesthetic may not spread to the intercostal space in the thoracic cage in M-TAPA. Further studies are required to confirm the precise mechanism of action and efficacy of M-TAPA in a large sample of human participants.

DOI： 10.1136/rapm-2022-104275

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BACKGROUND: Traumatic brain injury (TBI) initiates immune responses involving infiltration of monocyte-derived macrophages (MDMs) in the injured brain tissue. These MDMs play a key role in perioperative neurocognitive disorders (PNDs). We tested the hypothesis that preanesthetic treatment with dexmedetomidine (DEX) could suppress infiltration of MDMs into the hippocampus of TBI model mice, ameliorating PND. METHODS: We first performed bone marrow transplantation from green fluorescent protein-transgenic mice to C57BL/6 mice to identify MDMs. We used only male mice for homogeneity. Four weeks after transplantation, a controlled cortical impact model of TBI was created using recipient mice. Four weeks after TBI, mice received pretreatment with DEX before general anesthesia (GA). Mice performed the Barnes maze test (8-12 mice/group) 2 weeks after GA and were euthanized for immunohistochemistry (4-5 mice/group) or immunoblotting (7 mice/group) 4 weeks after GA. RESULTS: In Barnes maze tests, TBI model mice showed longer primary latency (mean difference, 76.5 [95% confidence interval, 41.4-111.6], P < .0001 versus Naïve), primary path length (431.2 [98.5-763.9], P = .001 versus Naïve), and more primary errors (5.7 [0.62-10.7], P = .017 versus Naïve) than Naïve mice on experimental day 3. Expression of MDMs in the hippocampus was significantly increased in TBI mice compared to Naïve mice (2.1 [0.6-3.7], P = .003 versus Naïve). Expression of monocyte chemotactic protein-1 (MCP1)-positive areas in the hippocampus was significantly increased in TBI mice compared to Naïve mice (0.38 [0.09-0.68], P = .007 versus Naïve). Immunoblotting indicated significantly increased expression of interleukin-1β in the hippocampus in TBI mice compared to Naïve mice (1.59 [0.08-3.1], P = .035 versus Naïve). In contrast, TBI mice pretreated with DEX were rescued from these changes and showed no significant difference from Naïve mice. Yohimbine, an α2 receptor antagonist, mitigated the effects of DEX (primary latency: 68.3 [36.5-100.1], P < .0001 versus TBI-DEX; primary path length: 414.9 [120.0-709.9], P = .0002 versus DEX; primary errors: 6.6 [2.1-11.2], P = .0005 versus TBI-DEX; expression of MDMs: 2.9 [1.4-4.4], P = .0001 versus TBI-DEX; expression of MCP1: 0.4 [0.05-0.67], P = .017 versus TBI-DEX; expression of interleukin-1β: 1.8 [0.34-3.35], P = .01 versus TBI-DEX). CONCLUSIONS: Preanesthetic treatment with DEX suppressed infiltration of MDMs in the hippocampus and ameliorated PND in TBI model mice. Preanesthetic treatment with DEX appears to suppress infiltration of MDMs in the hippocampus and may lead to new treatments for PND in patients with a history of TBI.

DOI： 10.1213/ANE.0000000000005699

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PURPOSE: Ultrasound-guided inferior alveolar nerve block (UGIANB) is a mandibular analgesic procedure in which local anesthetic is injected into the pterygomandibular space (PMS). Several studies have reported the clinical efficacy of UGIANB for mandibular surgeries; however, its effective range has never been investigated. We performed a cadaveric study to investigate the success rate of UGIANB injections and to determine whether injected dye could stain the mandibular nerve (MN) trunk and its branches. METHODS: We performed UGIANB on the bilateral faces of 4 Thiel-embalmed cadavers. A needle was advanced to the PMS under ultrasound guidance and 5 mL of dye was injected. The cadaver was dissected and inspected for the presence of dye in the PMS; the range of dye spread to any of the inferior alveolar nerve (IAN), lingual nerve (LN), buccal nerve (BN), mandibular nerve (MN), auriculotemporal nerve (ATN), or facial nerves; and for the presence of intravascular dye. RESULTS: We performed eight UGIANB procedures on four cadavers. Dye was observed in the PMS in 7/8 injections. Staining was observed in all IAN, LN, and BNs that could be identified at dissection. No MN or auriculotemporal nerves (ATNs) were stained in any injections. No intravascular dye was observed in any injections. CONCLUSIONS: UGIANB can administer anesthetic into the PMS with high accuracy. UGIANB injections reached the IAN, LN, and BNs, but did not reach the MN or ATNs located outside the PMS. The findings of this cadaveric study indicate that UGIANB can provide sufficient analgesia for mandibular surgeries.

DOI： 10.1007/s00540-021-03004-9

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Elevating neuroprotective proteins using adeno-associated virus (AAV)-mediated gene delivery shows great promise in combating devastating neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is one such disease resulting from loss of upper and lower motor neurons (MNs) with 90-95% of cases sporadic (SALS) in nature. Due to the unknown etiology of SALS, interventions that afford neuronal protection and preservation are urgently needed. Caveolin-1 (Cav-1), a membrane/lipid rafts (MLRs) scaffolding and neuroprotective protein, and MLR-associated signaling components are decreased in degenerating neurons in postmortem human brains. We previously showed that, when crossing our SynCav1 transgenic mouse (TG) with the mutant human superoxide dismutase 1 (hSOD1G93A) mouse model of ALS, the double transgenic mouse (SynCav1 TG/hSOD1G93A) exhibited better motor function and longer survival. The objective of the current study was to test whether neuron-targeted Cav-1 upregulation in the spinal cord using AAV9-SynCav1 could improve motor function and extend longevity in mutant humanized mouse and rat (hSOD1G93A) models of familial (F)ALS. Methods: Motor function was assessed by voluntary running wheel (RW) in mice and forelimb grip strength (GS) and motor evoked potentials (MEP) in rats. Immunofluorescence (IF) microscopy for choline acetyltransferase (ChAT) was used to assess MN morphology. Neuromuscular junctions (NMJs) were measured by bungarotoxin-a (Btx-a) and synaptophysin IF. Body weight (BW) was measured weekly, and the survival curve was determined by Kaplan-Meier analysis. Results: Following subpial gene delivery to the lumbar spinal cord, male and female hSOD1G93A mice treated with SynCav1 exhibited delayed disease onset, greater running-wheel performance, preserved spinal alpha-motor neuron morphology and NMJ integrity, and 10% increased longevity, independent of affecting expression of the mutant hSOD1G93A protein. Cervical subpial SynCav1 delivery to hSOD1G93A rats preserved forelimb GS and MEPs in the brachial and gastrocnemius muscles. Conclusion: In summary, subpial delivery of SynCav1 protects and preserves spinal motor neurons, and extends longevity in a familial mouse model of ALS without reducing the toxic monogenic component. Furthermore, subpial SynCav1 delivery preserved neuromuscular function in a rat model of FALS. The latter findings strongly indicate the therapeutic applicability of SynCav1 to treat ALS attributed to monogenic (FALS) and potentially in sporadic cases (i.e., SALS).

DOI： 10.7150/thno.72614

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PURPOSE: Immobilization of the cervical spine after trauma is recommended as standard care to prevent secondary injury. We tested the hypothesis that a two-handed airway maneuver, consisting of mandibular advancement and mouth opening in the neutral neck position, would minimize changes in the angle of the cervical vertebrae at the C0/4 level and tidal volume in non-obese patients under anesthesia with neuromuscular blockade. METHODS: Twenty consecutive patients without cervical spine injury undergoing general anesthesia were enrolled and evaluated. The primary variable was change in the angle of the cervical vertebrae at the C0/4 level during mask ventilation using the modified two-handed technique. Secondary variables included changes in the angles of the cervical vertebrae at each level between C0 and C4, anterior movement of the vertebral bodies, change in the angle between the head and neck, change in the pharyngeal airway space, and tidal volume during mask ventilation. RESULTS: The two-handed airway maneuver of mandibular advancement and mouth opening resulted in statistically significant changes in the angle of the cervical spine at the C0/4 level (3.2 ± 3.0 degrees, P < 0.001) and the C3/4 level (1.4 ± 2.2 degrees, P = 0.01). The two-handed airway maneuver provided adequate mask ventilation without anterior movement of the vertebral bodies. CONCLUSION: Our study suggests that a two-handed airway maneuver of mandibular advancement and mouth opening in the neutral neck position results in only slight change in the cervical vertebral angle at the C0/4 level in non-obese patients under general anesthesia with neuromuscular blockade.

DOI： 10.1007/s00540-021-02981-1

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PURPOSE: The newly introduced erector spinae plane block (ESPB) has given anesthesiologists an alternative regional anesthetic technique for thoracic analgesia. Although ESPB and retrolaminar block (RLB) have similar puncture sites, no clinical study comparing ESPB and RLB has been reported. The aim of this study was to compare ESPB and RLB in terms of analgesic efficacy in the context of multimodal analgesia following breast surgery. METHODS: Fifty female patients undergoing breast surgery under general anesthesia were randomly allocated to receive either ultrasound-guided ESPB or RLB with 20 mL of 0.375% levobupivacaine for postoperative analgesia. The primary outcome was analgesic efficacy in terms of time to first postoperative rescue analgesic after the block procedure. The secondary outcomes were consumption of remifentanil during anesthesia, pain intensity at rest for 24 h postoperatively, and occurrence of postoperative nausea and vomiting (PONV). RESULTS: After excluding five patients, 45 patients (22 and 23 patients in the ESPB and RLB group, respectively) were analyzed. Median time until the first postoperative rescue analgesic after the block procedure in the ESPB group was not significantly longer than that in the RLB group (8.6 [range 2.7-24] vs. 4.8 [3.0-24] h; P = 0.83). There was no significant difference in the consumption of remifentanil during anesthesia, pain intensity at rest for 24 h postoperatively, and occurrence of PONV between the two groups. CONCLUSION: ESPB is equivalent, and not superior, to RLB for postoperative analgesia after breast surgery when 20 mL of 0.375% levobupivacaine is injected at the fourth thoracic vertebra.

DOI： 10.1007/s00540-020-02855-y

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Language：Japanese   Publisher：真興交易(株)医書出版部  

2020年8月に、ベンゾジアゼピン受容体系静脈麻酔薬であるレミマゾラムを全身麻酔薬として使用することが可能となった。レミマゾラムは水溶性薬剤であることから、プロポフォール注入時にみられる血管痛がない。また、ベンゾジアゼピン系麻酔薬であることから、フルマゼニルによる拮抗が可能である。レミマゾラムの薬理学的特性、臨床試験の概要、臨床使用時の注意点とレミマゾラムの可能性について述べた。

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Bilateral continuous phrenic nerve block effectively regulates refractory persistent, strong inspiratory effort in a patient with coronavirus disease (COVID-19). A 73-year-old man with acute respiratory distress syndrome (ARDS) due to COVID-19 was admitted to the intensive care unit (ICU). Use of neuromuscular blocking agents (NMBAs) was stopped due to uncontrollable strong inspiratory efforts and worsened lung injury. We performed bilateral continuous phrenic nerve block, which suppressed inspiratory efforts, resulting in lung injury improvement. A bilateral continuous phrenic nerve block is a viable alternative to control refractory strong inspiratory effort leading to lung injury in cases with prolonged NMBA use.

DOI： 10.1016/j.rmcr.2021.101455

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Interventions that preserve motor neurons or restore functional motor neuroplasticity may extend longevity in amyotrophic lateral sclerosis (ALS). Delivery of neurotrophins may potentially revive degenerating motor neurons, yet this approach is dependent on the proper subcellular localization of neurotrophin receptor (NTR) to plasmalemmal signaling microdomains, termed membrane/lipid rafts (MLRs). We previously showed that overexpression of synapsin-driven caveolin-1 (Cav-1) (SynCav1) increases MLR localization of NTR [e.g., receptor tyrosine kinase B (TrkB)], promotes hippocampal synaptic and neuroplasticity, and significantly improves learning and memory in aged mice. The present study crossed a SynCav1 transgene-positive (SynCav1+) mouse with the mutant human superoxide dismutase glycine to alanine point mutation at amino acid 93 (hSOD1G93A) mouse model of ALS. When compared with hSOD1G93A, hSOD1G93A/SynCav1+ mice exhibited greater body weight and longer survival as well as better motor function. Microscopic analyses of hSOD1G93A/SynCav1+ spinal cords revealed preserved spinal cord α-motor neurons and preserved mitochondrial morphology. Moreover, hSOD1G93A/SynCav1+ spinal cords contained more MLRs (cholera toxin subunit B positive) and MLR-associated TrkB and Cav-1 protein expression. These findings demonstrate that SynCav1 delays disease progression in a mouse model of ALS, potentially by preserving or restoring NTR expression and localization to MLRs.-Sawada, A., Wang, S., Jian, M., Leem, J., Wackerbarth, J., Egawa, J., Schilling, J. M., Platoshyn, O., Zemljic-Harpf, A., Roth, D. M., Patel, H. H., Patel, P. M., Marsala, M., Head, B. P. Neuron-targeted caveolin-1 improves neuromuscular function and extends survival in SOD1G93A mice.

DOI： 10.1096/fj.201802652RR

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BACKGROUND: Anesthetic considerations for surgery during pregnancy include the safety of both mother and fetus. We successfully administered anesthesia for total mastectomy to a pregnant woman using general anesthesia combined with continuous erector spinae plane block. CASE PRESENTATION: A 41-year-old woman was scheduled to undergo total mastectomy at 18 weeks' gestation. Hence, we decided to administer general anesthesia combined with continuous erector spinae plane block to minimize physiological stress on both mother and fetus. Continuous erector spinae plane block provided sufficient postoperative analgesia for our patient, completely eliminating the need for additional rescue analgesia during the entire postoperative period. CONCLUSIONS: General anesthesia combined with continuous erector spinae plane block provided adequate analgesia without maternal hypotension in a pregnant woman undergoing total mastectomy.

DOI： 10.1186/s40981-019-0245-y

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BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) present increased risks for anesthesia-related complications. We present a case of epidural anesthesia combined with sedation with dexmedetomidine for open appendectomy in a patient with ALS who refused invasive mechanical ventilation. CASE PRESENTATION: A 50-year-old man with a 3-year history of ALS was scheduled to undergo open appendectomy due to repeated appendicitis. He refused to undergo invasive mechanical ventilation using an endotracheal tube. Hence, we decided to administer epidural anesthesia combined with sedation with dexmedetomidine for anesthesia during the surgical procedure. The patient underwent open appendectomy without complications and with no pain or discomfort during surgery. There were no neurological complications at the 3-month follow-up after surgery. CONCLUSIONS: Epidural anesthesia combined with sedation with dexmedetomidine may be effective for the anesthetic management of patients who would benefit from regional anesthesia.

DOI： 10.1186/s40981-018-0220-z

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We report three cases of implantation of the SureScan® system and magnetic resonance imaging (MRI) for investigating causes of pain. Although there were metal-induced artifacts on the MR images of 2 patients, the artifacts did not affect the images of structures that needed to be assessed to make the diagnosis. The SureScan® system enabled patients implanted with spinal cord stimulation devices to undergo MRI.

DOI： 10.1007/s00540-017-2413-4

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Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

DOI： 10.1096/fj.201601288RRR

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Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.

DOI： 10.1007/s10571-016-0400-1

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BACKGROUND: A harmful effect of stress hormone secretion during surgery is lipolysis and proteolysis to maintain normal blood glucose levels. A well-titrated general anesthetic improves blood glucose control by suppressing secretion of these stress hormones. The aim of this study was to explore the effect of intraoperative glucose infusion on lipolysis and proteolysis in patients undergoing a general anesthetic consisting of sevoflurane and remifentanil during long (>6 hours) major surgery. METHODS: In this prospective, single-blinded, randomized, multicenter trial, 80 patients with an expected duration of anesthesia of >6 hours were allocated to either the glucose group, consisting of 40 patients who were infused with acetated Ringer's solution with glucose (2 mg/kg/min), or the no glucose group, consisting of 40 patients who were infused with the same solution, but without glucose. After oxygenation, general anesthesia was induced with propofol, fentanyl, and rocuronium and was maintained with sevoflurane, oxygen, rocuronium, and remifentanil infusions. The rates of remifentanil infusion were titrated based on systolic arterial blood pressure, maintaining this parameter within 10% of its postanesthesia values. Seventy-four patients completed the study. Urinary 3-methylhistidine/creatinine (3-MH/Cre) ratio, acetoacetic acid, 3-hydroxybutyric acid, blood glucose, insulin, and cortisol were measured 3 times: at anesthesia induction (0 hour) and at 3 and 6 hours after anesthesia induction. Urinary 3-MH/Cre ratio was the primary study outcome. RESULTS: In the no glucose group, the urinary 3-MH/Cre ratio at 6 hours was increased compared with that at 0 hour (213 [range, 42-1903] vs 124 [18-672] nmol/μmol; the difference in medians, 89; the 95% confidence interval [CI] of the difference, 82-252; P = .0002). Acetoacetic acid and 3-hydroxybutyric acid levels in the no glucose group were greater than those in the glucose group at 6 hours (110 [8-1036] vs 11 [2-238] μmol/L; the difference in medians, 99; the 95% CI of the difference, 92-196; P < .0001 and 481 [15-2783] vs 19 [4-555] μmol/L; the difference in medians, 462; the 95% CI of the difference, 367-675; P < 0.0001, respectively). Blood glucose and insulin levels in the glucose group were greater than those in the no glucose group at 3 hours (146 [103-190] vs 93 [72-124] mg/dL; the difference in medians, 53; the 95% CI of the difference, 47-55; P < .0001 and 9.8 [1.2-25.4] vs 3.2 [0.4-15.0] μU/mL; the difference in medians, 6.5; the 95% CI of the difference, 4.8-6.8; P < .0001) and 6 hours (139 [92-189] vs 87 [68-126] mg/dL; the difference in medians, 52; the 95% CI of the difference, 44-58; P < .0001 and 8.1 [1.2-22.3] vs 3.2 [0.4-10.1] μU/mL; the difference in medians, 4.9; the 95% CI of the difference, 4.0-5.9; P < .0001). Cortisol levels in both groups were similarly within normal levels at 0, 3, and 6 hours. CONCLUSIONS: The study showed that intraoperative glucose infusion suppressed lipolysis and proteolysis in patients anesthetized with remifentanil in combination with sevoflurane during surgery of >6 hours in length.

DOI： 10.1213/ANE.0000000000001522

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Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and allodynia, and emotional abnormalities such as anxiety and depression. Although spinal cord microglia are involved in abnormal sensitivity to neuropathic pain, no previous studies have examined the mechanism of neuropathic pain-induced anxiety. Here, we examined the involvement of bone marrow (BM)-derived microglia aggregated in the amygdalae of mice with chronic neuropathic pain in the development of anxiety-like behavior. We prepared partial sciatic nerve ligations (PSNL) in mice that received bone marrow transplantation from green fluorescent protein (GFP)-Tg mice after irradiation with head protection, and examined GFP-positive microglia in the central nuclei of the amygdalae (CeA). On day 28 after PSNL, BM-derived microglia aggregated in the CeA concurrent with anxiety-like behavior. BM-derived microglia in the CeA highly expressed interleukin (IL)-1β and C-C chemokine receptor type 2 (CCR2). In addition, neurons in the CeA highly expressed monocyte chemotactic protein-1 (MCP-1), a ligand for CCR2, in PSNL-treated mice compared to sham-operated mice, suggesting that the MCP-1/CCR2 axis is involved in the recruitment of BM-derived microglia. Oral administration of a CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and successfully reversed the anxiety-like behavior and hypersensitivity to mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1β receptor antagonist directly into the CeA successfully reversed the anxiety-like behavior in the PSNL-treated mice even though the neuropathic pain persisted. These results suggest that the recruitment of BM-derived microglia to the CeA via the MCP-1/CCR2 axis and neuron-microglia interactions might be important in the pathogenesis of neuropathic pain-induced anxiety.

DOI： 10.1016/j.pain.2014.05.031

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BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS) induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN) of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(low)CCR2(+)CXCR4(high), as distinct from CX3CR1(high)CCR2(-)CXCR4(low) resident microglia, and express higher levels of interleukin-1β (IL-1β) but lower levels of tumor necrosis factor-α (TNF-α). Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1) in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1) in the bone marrow and increases the frequency of CXCR4(+) monocytes in peripheral circulation. And then a chemokine (C-C motif) receptor 2 (CCR2) or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

DOI： 10.1371/journal.pone.0081744

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Language：English   Publishing type：Research paper (scientific journal)  

Epidrum(®) is an optimal pressure, loss of resistance device for identifying the epidural space. We investigated the usefulness of Epidrum versus the loss of resistance or hanging drop techniques while performing epidural anesthesia. Eighty adult patients who were scheduled for elective surgery under lumbar epidural anesthesia were randomized into two groups. The first group (Epidrum group) consisted of 40 adult patients who were scheduled for epidural anesthesia using Epidrum. The second group (control group) consisted of 40 adult patients who were scheduled for epidural anesthesia using the loss of resistance or hanging drop technique. We recorded the time required to identify the epidural space and outcomes of epidural catheterization. The attending anesthesiologists were also questioned regarding the ease of control of the Tuohy needle and of epidural space identification with each method. The time required to perform epidural anesthesia was significantly shorter in the Epidrum group than in the control group [28 s (10-76) vs. 90 s (34-185); median (interquartile range)] (p < 0.05). Tuohy needle control was significantly easier in the Epidrum group than in the control group (p < 0.05). Epidrum is useful for performing epidural anesthesia quickly while obtaining good Tuohy needle control.

DOI： 10.1007/s00540-011-1278-1

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

We report anesthetic management of caesarean section using common iliac artery balloon occlusion in 6 patients with placenta previa. Placenta previa might induce critical hemorrhage during caesarean section. We performed caesarean section safely, with preoperative placement of occlusive balloon catheters in the bilateral common iliac arteries. This technique provided satisfactory condition for control of bleeding during the operation. There was no perioperative complication in these patients. Common iliac artery balloon occlusion could reduce blood loss during caesarean section in patients with placenta previa.

PubMed

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