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BACKGROUND: Near-falls should be detected to prevent falls related to the earlier ambulation after Total knee arthroplasty (TKA). The quadriceps weakness with femoral nerve block (FNB) has led to a focus on adductor canal block (ACB). We purposed to examine the risk of falls and the earlier ambulation in each continuous infusion nerve block. METHODS: Continuous infusion nerve block (FNB or ACB) was performed until postoperative day (POD) 2 or 3. Pain levels and falls/near-falls with knee-buckling were monitored from POD 1 to POD 3. The score on the manual muscle test, MMT (0 to 5, 5 being normal), of the patients who could ambulate on POD 1, was investigated. RESULTS: A total of 73 TKA cases, 36 FNB and 37 ACB, met the inclusion criteria. No falls were noted. But episodes of near-falls with knee-buckling were witnessed in 14 (39%) cases in the FNB group and in 4 (11%) in the ACB group (p = 0.0068). In the ACB group, 81.1% of patients could ambulate with parallel bars on POD 1, while only 44.4% of FNB patients could do so (p = 0.0019). The quadriceps MMT values in the ACB group was 2.82, significantly higher than 1.97 in the FNB group (p = 0.0035). There were no significant differences in pain as measured with a numerical rating scale (NRS) and rescue analgesia through POD 3. CONCLUSION: ACB was associated with significantly less knee-buckling and earlier ambulation post-TKA, with better quadriceps strength. Our study indicated the incidence of falls and near-falls with continuous infusion nerve blocks, and support the use of ACB to reduce the risk of falls after TKA. It is suggested that a certain number of the patients even with continuous ACB infusion should be considered with the effect of motor branch to prevent falls.
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Artroplastia de Reemplazo de Rodilla , Bloqueo Nervioso , Analgésicos Opioides , Anestésicos Locales , Artroplastia de Reemplazo de Rodilla/efectos adversos , Nervio Femoral , Humanos , Fuerza Muscular , Bloqueo Nervioso/efectos adversos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Proyectos Piloto , Estudios Retrospectivos , CaminataRESUMEN
BACKGROUND: An epidurally administered local anesthetic acts primarily on the epidural nerve roots and can act directly on the spinal cord through the dural sleeve. We hypothesized that epidurally administered ropivacaine would reduce the amplitude of transcranial electrical motor-evoked potentials by blocking nerve conduction in the spinal cord. Therefore, we conducted a double-blind, randomized, controlled trial. METHODS: Thirty adult patients who underwent lung surgery were randomly allocated to 1 of 3 groups, based on the ropivacaine concentration: the 0.2% group, the 0.375% group, and the 0.75% group. The attending anesthesiologists, neurophysiologists, and patients were blinded to the allocation. The epidural catheter was inserted at the T5-6 or T6-7 interspace by a paramedian approach, using the loss of resistance technique with normal saline. General anesthesia was induced and maintained using propofol and remifentanil. Transcranial electrical motor-evoked potentials were elicited by a train of 5 pulses with an interstimulus interval of 2 milliseconds by using a constant-voltage stimulator and were recorded from the tibialis anterior muscle. Somatosensory-evoked potentials (SSEPs) were evoked by electrical tibial nerve stimulation at the popliteal fossa. After measuring the baseline values of these evoked potentials, 10 mL of epidural ropivacaine was administered at the 0.2%, 0.375%, or 0.75% concentration. The baseline amplitudes and latencies recorded before administering ropivacaine were defined as 100%. Our primary end point was the relative amplitude of the motor-evoked potentials at 60 minutes after the epidural administration of ropivacaine. We analyzed the amplitudes and latencies of these evoked potentials by using the Kruskal-Wallis test and used the Dunn multiple comparison test as the post hoc test for statistical analysis. RESULTS: The data are expressed as the median (interquartile range). Sixty minutes after epidurally administering ropivacaine, the motor-evoked potential amplitude was lower in the 0.75% group (7% [3%-18%], between-group difference P < .001) and in the 0.375% group (52% [43%-59%]) compared to that in the 0.2% group (96% [89%-105%]). The latency of SSEP was longer in the 0.75% group compared to that in the 0.2% group, but the amplitude was unaffected. CONCLUSIONS: Epidurally administered high-dose ropivacaine lowered the amplitude of motor-evoked potentials and prolonged the onset latencies of motor-evoked potentials and SSEPs compared to those in the low-dose group. High-dose ropivacaine can act on the motor pathway through the dura mater.
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Anestesia Epidural , Anestésicos Locales/administración & dosificación , Potenciales Evocados Motores/efectos de los fármacos , Monitorización Neurofisiológica Intraoperatoria , Procedimientos Quirúrgicos Pulmonares , Tractos Piramidales/efectos de los fármacos , Ropivacaína/administración & dosificación , Estimulación Transcraneal de Corriente Directa , Anciano , Anestesia Epidural/efectos adversos , Anestesia General , Anestésicos Locales/efectos adversos , Método Doble Ciego , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Pulmonares/efectos adversos , Tiempo de Reacción , Ropivacaína/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Low-dose droperidol has been widely used as an antiemetic during and after surgery. Although high-dose droperidol affects motor-evoked potential, the effects of low-dose droperidol on motor-evoked potential amplitude are unclear. The aim of this study was to investigate whether low-dose droperidol affects motor-evoked potential amplitude. We retrospectively reviewed the data of patients who underwent spine surgery under general anesthesia with motor-evoked potential monitoring from February 2016 to 2017. The outcome was the motor-evoked potential amplitude of the bilateral abductor pollicis brevis muscle, tibialis anterior muscle, and abductor hallucis muscle within 1 and 1-2 h after droperidol administration, compared with the baseline motor-evoked potential value. Thirty-four patients were analyzed. The median dose of droperidol was 21 µg/kg. The motor-evoked potential amplitudes of all muscles were significantly reduced after droperidol administration and recovered to baseline values within 2 h. The reduction of all motor-evoked potential amplitudes after droperidol administration was 37-45% of baseline values. There were no significant differences in other drugs administered. There were no serious adverse effects of droperidol administration. Motor-evoked potential amplitude was suppressed by low-dose droperidol. During intraoperative motor-evoked potential monitoring in spine surgery, anesthesiologists should pay careful attention to the timing of administration of droperidol, even at low doses. Based on the results of this study, we are conducting a randomized controlled trial.
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Droperidol , Potenciales Evocados Motores , Anestesia General , Humanos , Monitoreo Intraoperatorio , Estudios RetrospectivosRESUMEN
PURPOSE: Propofol inhibits the amplitudes of transcranial electrical motor-evoked potentials (TCE-MEP) in a dose-dependent manner. However, the mechanisms of this effect remain unknown. Hence, we investigated the spinal mechanisms of the inhibitory effect of propofol on TCE-MEP amplitudes by evaluating evoked electromyograms (H-reflex and F-wave) under general anesthesia. METHODS: We conducted a prospective, single-arm, interventional study including 15 patients scheduled for spine surgery under general anesthesia. Evoked electromyograms of the soleus muscle and TCE-MEPs were measured at three propofol concentrations using target-controlled infusion (TCI: 2.0, 3.0, and 4.0 µg/mL). The primary outcome measure was the left H-reflex amplitude during TCI of 4.0- compared to 2.0-µg/mL propofol administration. RESULTS: The median [interquartile range] amplitudes of the left H-reflex were 4.71 [3.42-6.60] and 5.6 [4.17-7.46] in the 4.0- and 2.0-µg/mL TCI groups (p = 0.4, Friedman test), respectively. There were no significant differences in the amplitudes of the right H-reflex and the bilateral F-wave among these groups. However, the TCE-MEP amplitudes significantly decreased with increased propofol concentrations (p < 0.001, Friedman test). CONCLUSION: Propofol did not affect the amplitudes of the H-reflex and the F-wave, whereas TCE-MEP amplitudes were reduced at higher propofol concentrations. These results suggested that propofol can suppress the TCE-MEP amplitude by inhibiting the supraspinal motor pathways more strongly than the excitability of the motor neurons in the spinal cord.
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Propofol , Potenciales Evocados Motores , Humanos , Monitoreo Intraoperatorio , Neuronas Motoras , Propofol/farmacología , Estudios ProspectivosRESUMEN
PURPOSE: Emergence delirium (ED) is a common postoperative complication of ambulatory pediatric surgery done under general anesthesia with sevoflurane. However, perioperative analgesic techniques have been shown to reduce sevoflurane-induced ED. The primary objective of this investigation was to examine whether an ultrasound-guided ilioinguinal/iliohypogastric (II/IH) nerve block for ambulatory pediatric inguinal hernia repair could reduce the incidence of sevoflurane-induced ED. METHODS: The subjects of this prospective randomized double-blind study were 40 boys ranging in age from 1 to 6 years, who were scheduled to undergo ambulatory inguinal hernia repair. The patients were randomized to either receive or not to receive an ultrasound-guided II/IH nerve block (Group B and Group NB, respectively). General anesthesia was maintained with sevoflurane and nitrous oxide. The primary outcome assessed was ED, evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale 30 min after emergence from general anesthesia. The secondary outcomes assessed were postoperative pain, evaluated using the Behavioral Observational Pain Scale (BOPS), and the amount of intra-operative sevoflurane given. RESULTS: The median PAED scale scores did not differ between Groups B and NB at 30 min (P = 0.41). BOPS scores also did not differ significantly between the groups, but the mean amount of intraoperative sevoflurane given was significantly lower in Group B than in Group NB (P < 0.01). CONCLUSIONS: Ultrasound-guided II/IH nerve block for ambulatory pediatric inguinal hernia repair did not reduce ED, but it did decrease the amount of intra-operative sevoflurane needed. CLINICAL TRIAL REGISTRATION: UMIN000008586.
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Procedimientos Quirúrgicos Ambulatorios , Delirio del Despertar , Hernia Inguinal/cirugía , Herniorrafia , Bloqueo Nervioso/métodos , Complicaciones Posoperatorias , Ultrasonografía , Anestesia General/efectos adversos , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , Niño , Preescolar , Método Doble Ciego , Delirio del Despertar/etiología , Delirio del Despertar/prevención & control , Humanos , Lactante , Masculino , Éteres Metílicos/administración & dosificación , Éteres Metílicos/efectos adversos , Atención Perioperativa/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , SevofluranoRESUMEN
This is the first case report describing the epidural misplacement of an infusion catheter, which was intended to be located in the thoracic paravertebral space using an ultrasound-guided technique. The patient was a 57-year-old female undergoing a laparoscopy-assisted left partial nephrectomy. Before surgery, a Tuohy needle was inserted into the paravertebral space at the left ninth intercostal space using an in-plane transverse ultrasound-guided approach in the lateral-to-medial direction. A catheter was then threaded into the paravertebral space through the needle. Subsequently, the catheter position was secured, although ultrasound-guided confirmation of air injected through the catheter into the paravertebral space was not obtained. Twenty milliliters of 0.5 % levobupivacaine was administered through the catheter at both the initiation and conclusion of surgery. A neurologic examination following surgery revealed paraplegia, along with sensory deficits in the bilateral T3-S5 dermatome. The motor dysfunction in the lower extremities lasted 7 h, and the sensory block lasted 13.5 h. Postoperative radiologic confirmation of the catheter position concomitant with the spread of radiopaque dye revealed that the tip of the catheter was lying in the epidural space. Unless precise attention is paid to detection of the catheter tip location, a thoracic paravertebral catheter can enter into the epidural space even under ultrasound guidance.
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Bupivacaína/análogos & derivados , Bloqueo Nervioso/efectos adversos , Ultrasonografía/métodos , Bupivacaína/administración & dosificación , Cateterismo/efectos adversos , Cateterismo/métodos , Catéteres , Espacio Epidural , Femenino , Humanos , Levobupivacaína , Persona de Mediana Edad , Agujas , Bloqueo Nervioso/métodosRESUMEN
BACKGROUND: Some anesthetic drugs reduce the amplitude of transcranial electrical motor-evoked potentials (MEPs). Remimazolam, a new benzodiazepine, has been suggested to have little effect on MEP amplitude. This prospective, preliminary, dose-escalation study aimed to assess whether remimazolam is associated with lower MEP amplitude in a dose-dependent manner. METHODS: Ten adult patients scheduled for posterior spinal fusion were included in this study. General anesthesia was induced with a continuous infusion of remifentanil and remimazolam. After the patient lost consciousness, the infusion rate of remimazolam was set to 1 mg/kg/h, and the patient underwent tracheal intubation. Baseline MEPs were recorded under 1 mg/kg/h of remimazolam in a prone position. Thereafter, the infusion rate of remimazolam was increased to 2 mg/kg/h, with a bolus of 0.1 mg/kg. Ten minutes after the increment, the evoked potentials were then recorded again. The primary endpoint was the MEP amplitude recorded in the left gastrocnemius muscle at 2 time points. RESULTS: There was no difference in MEP amplitude recorded from the left gastrocnemius muscle before and after increasing remimazolam (median [interquartile range]: 0.93 [0.65 to 1.25] mV and 0.70 [0.43 to 1.26] mV, respectively; P=0.08). The average time from the cessation of remimazolam administration to neurological examination after surgery was 4 minutes using flumazenil. CONCLUSIONS: This preliminary study suggests that increasing remimazolam from 1 to 2 mg/kg/h might have an insignificant effect on transcranial electric MEPs.
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ABSTRACT: Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 µg) induced short-term (<24 hours) mechanical allodynia and heat hyperalgesia, a response that is compromised in Tlr7-/- or Trpa1-/- mice. Ex vivo and in vivo calcium imaging in GCaMP6-report mice revealed increased calcium signal in spinal cord afferent terminals and doral root ganglion/dorsal root ganglia neurons following spinal perfusion and intraplantar injection of let-7b. Patch-clamp recordings also demonstrated enhanced excitatory synaptic transmission (miniature excitatory postsynaptic currents [EPSCs]) in spinal nociceptive neurons following let-7b perfusion or optogenetic activation of axonal terminals. The elevation in spinal calcium signaling and EPSCs was dependent on the presence of toll-like receptor-7 (TLR7) and transient receptor potential ion channel subtype A1 (TRPA1). In addition, endogenous let-7b is enriched in spinal cord synaptosome, and peripheral inflammation increased let-7b in doral root ganglion/dorsal root ganglia neurons, spinal cord tissue, and the cerebrospinal fluid. Notably, let-7b antagomir inhibited inflammatory pain and inflammation-induced synaptic plasticity (EPSC increase), suggesting an endogenous role of let-7b in regulating pain and synaptic transmission. Furthermore, intrathecal injection of let-7b, at a higher dose (10 µg), induced persistent mechanical allodynia for >2 weeks, which was abolished in Tlr7-/- mice. The high dose of let-7b also induced microgliosis in the spinal cord. Of interest, intrathecal minocycline only inhibited let-7b-induced mechanical allodynia in male but not female mice. Our findings indicate that the secreted microRNA let-7b has the capacity to provoke pain through both neuronal and glial signaling, thereby establishing miRNA as an emerging neuromodulator.
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MicroARNs , Microglía , Médula Espinal , Transmisión Sináptica , Animales , Masculino , Ratones , Potenciales Postsinápticos Excitadores/fisiología , Ganglios Espinales/metabolismo , Hiperalgesia/fisiopatología , Hiperalgesia/metabolismo , Glicoproteínas de Membrana , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neuronas/metabolismo , Nociceptores/metabolismo , Nociceptores/fisiología , Transducción de Señal/fisiología , Médula Espinal/metabolismo , Médula Espinal/fisiopatología , Transmisión Sináptica/fisiología , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 7/genética , Canal Catiónico TRPA1/metabolismo , Canal Catiónico TRPA1/genéticaRESUMEN
INTRODUCTION: Although multimodal intraoperative neuromonitoring (IONM), which has high sensitivity and specificity, is typically performed during spinal deformity surgery, neurological status may deteriorate with delay after surgical maneuvers. Here, we report a rare case of delayed postoperative neurological deficit (DPND) that was not detected by IONM during posterior spinal fusion (PSF) for congenital scoliosis. CASE PRESENTATION: A 14-year-old male presented with congenital scoliosis associated with T3 and T10 hemivertebrae. Preoperative Cobb angle of proximal thoracic (PT) and main thoracic (MT) curves were 50° and 41°, respectively. PSF (T1-L1) without hemivertebrectomy was performed, and the curves were corrected to 31° and 21° in the PT and MT curves, respectively, without any abnormal findings in IONM, blood pressure, or hemoglobin level. However, postoperative neurological examination revealed complete loss of motor function. A revision surgery, release of the curve correction by removing the rods, was immediately performed and muscle strength completely recovered on the first postoperative day. Five days postoperatively, PSF was achieved with less curve correction (36° in the PT curve and 26° in the MT curve), without postoperative neurological deficits. DISCUSSION: Possible mechanisms of DPND in our patient are spinal cord ischemia due to spinal cord traction caused by scoliosis correction and spinal cord kinking by the pedicle at the concave side. Understanding the possible mechanisms of intra- and postoperative neural injury is essential for appropriate intervention in each situation. Additionally, IONM should be continued to at least skin closure to detect DPND observed in our patient.
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Escoliosis , Fusión Vertebral , Masculino , Humanos , Adolescente , Escoliosis/congénito , Escoliosis/cirugía , Vértebras Torácicas/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Noxious stimuli activate nociceptive sensory neurons, causing action potential firing and the release of diverse signaling molecules. Several peptides have already been identified to be released by sensory neurons and shown to modulate inflammatory responses and inflammatory pain. However, it is still unclear whether lipid mediators can be released upon sensory neuron activation to modulate intercellular communication. Here, we analyzed the lipid secretome of capsaicin-stimulated nociceptive neurons with LC-HRMS, revealing that oleic acid is strongly released from sensory neurons by capsaicin. We further demonstrated that oleic acid inhibits capsaicin-induced calcium transients in sensory neurons and reverses bradykinin-induced TRPV1 sensitization by a calcineurin (CaN) and GPR40 (FFAR1) dependent pathway. Additionally, oleic acid alleviated zymosan-mediated thermal hypersensitivity via the GPR40, suggesting that the capsaicin-mediated oleic acid release from sensory neurons acts as a protective and feedback mechanism, preventing sensory neurons from nociceptive overstimulation via the GPR40/CaN/TRPV1-axis.
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Local anesthetics block impulses in peripheral nerves through the inhibition of voltage-gated sodium channels. However, the effects of local anesthetics may be more complex. It has been reported that local anesthetics not only block the impulses in nerve roots, but could also interact with many membrane phospholipids and proteins, including various receptors, and thereby affect a variety of cellular activities. In fact, there is evidence indicating that local anesthetics could inhibit NMDA-induced glutamatergic transmission in the spinal cord. Therefore, NMDA receptor antagonism of local anesthetics may have the possibility to prevent the patients from developing chronic pain. Furthermore, local anesthetics might have the possibility to prevent cancer cell proliferation like NMDA receptor antagonists. Local anesthetics have also been reported to have an inhibitory effect on other ion channel-coupled receptors, including 5-HT3, GABA, glycine, and nicotinic ACh receptors. Recently, the interaction between local anesthetics and TRPV1 agonist has attracted the attention because they raise the possibilities of producing analgesic effect without affecting motor or other sensory functions. The effects of local anesthetics may have some aspects which have not been clarified. Further investigations will be required to fully understand the actions of local anesthetics.
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Anestésicos Locales/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Analgésicos/farmacología , Animales , Dolor Crónico/tratamiento farmacológico , HumanosRESUMEN
Our understanding of neuropathic itch is limited due to a lack of relevant animal models. Patients with cutaneous T cell lymphoma (CTCL) experience severe itching. Here, we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune cell accumulation, and persistent pruritus. Intradermal CTCL inoculation produced time-dependent changes in nerve innervations in lymphoma-bearing skin. In the early phase (20 days), CTCL caused hyperinnervations in the epidermis. However, chronic itch was associated with loss of epidermal nerve fibers in the late phases (40 and 60 days). CTCL was also characterized by marked nerve innervations in mouse lymphoma. Blockade of C-fibers reduced pruritus at early and late phases, whereas blockade of A-fibers only suppressed late-phase itch. Intrathecal (i.t.) gabapentin injection reduced late-phase, but not early-phase, pruritus. IL-31 was upregulated in mouse lymphoma, whereas its receptor Il31ra was persistently upregulated in Trpv1-expressing sensory neurons in mice with CTCL. Intratumoral anti-IL-31 treatment effectively suppressed CTCL-induced scratching and alloknesis (mechanical itch). Finally, i.t. administration of a TLR4 antagonist attenuated pruritus in early and late phases and in both sexes. Collectively, we have established a mouse model of neuropathic and cancer itch with relevance to human disease. Our findings also suggest distinct mechanisms underlying acute, chronic, and neuropathic itch.
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Linfoma , Prurito , Animales , Femenino , Masculino , Ratones , Linfoma/complicaciones , Prurito/tratamiento farmacológico , Prurito/etiología , Células Receptoras Sensoriales , Piel/patología , Modelos Animales de EnfermedadRESUMEN
ABSTRACT: Specialized proresolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch are currently unknown. Recently, n-3 docosapentaenoic acid (DPA) was found to be a substrate for the biosynthesis of several novel families of SPMs and 3-oxa-PD1 n-3 DPA (3-oxa-PD1) is an oxidation-resistant metabolic stable analogue of the n-3 DPA-derived protectin D1 (PD1). In this article, we demonstrate that 3-oxa-PD1 effectively reduces both acute and chronic itch in mouse models. Intrathecal injection of 3-oxa-PD1 (100 ng) reduced acute itch induced by histamine, chloroquine, or morphine. Furthermore, intrathecal 3-oxa-PD1 effectively reduced chronic itch, induced by cutaneous T-cell lymphoma (CTCL), allergic contact dermatitis with dinitrofluorobenzene, and psoriasis by imiquimod. Intratumoral injection of 3-oxa-PD1 also suppressed CTCL-induced chronic itch. Strikingly, the antipruritic effect lasted for several weeks after 1-week intrathecal 3-oxa-PD1 treatment. Whole-cell recordings revealed significant increase in excitatory postsynaptic currents in spinal dorsal horn (SDH) neurons of CTCL mice, but this increase was blocked by 3-oxa-PD1. 3-oxa-PD1 further increased inhibitory postsynaptic currents in SDH neurons of CTCL mice. Cutaneous T-cell lymphoma increased the spinal levels of lipocalin-2 (LCN2), an itch mediator produced by astrocytes. 3-oxa-PD1 suppressed LCN2 production in CTCL mice and LCN2 secretion in astrocytes. Finally, CTCL-induced anxiety was alleviated by intrathecal 3-oxa-PD1. Our findings suggest that 3-oxa-PD1 potently inhibits acute and chronic itch through the regulation of excitatory or inhibitory synaptic transmission and astroglial LCN2 production. Therefore, stable SPM analogs such as 3-oxa-PD1 could be useful to treat pruritus associated with different skin injuries.
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Astrocitos , Ácidos Grasos Insaturados , Lipocalina 2 , Prurito , Animales , Ratones , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Ácidos Grasos Insaturados/farmacología , Ácidos Grasos Insaturados/uso terapéutico , Lipocalina 2/metabolismo , Linfoma Cutáneo de Células T/complicaciones , Ratones Endogámicos C57BL , Prurito/tratamiento farmacológico , Prurito/etiología , Prurito/metabolismo , Transmisión Sináptica/efectos de los fármacosRESUMEN
Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Mice lacking PD-1 (encoded by Pdcd1) exhibit enhanced long-term potentiation (LTP) and memory. Intraventricular administration of anti-mouse PD-1 monoclonal antibody (RMP1-14) potentiated learning and memory. Selective deletion of PD-1 in excitatory neurons (but not microglia) also enhances LTP and memory. Traumatic brain injury (TBI) impairs learning and memory, which is rescued by Pdcd1 deletion or intraventricular PD-1 blockade. Conversely, re-expression of Pdcd1 in PD-1-deficient hippocampal neurons suppresses memory and LTP. Exogenous PD-L1 suppresses learning/memory in mice and the excitability of mouse and NHP hippocampal neurons through PD-1. Notably, neuronal activation suppresses PD-L1 secretion, and PD-L1/PD-1 signaling is distinctly regulated by learning and TBI. Thus, conditions that reduce PD-L1 levels or PD-1 signaling could promote memory in both physiological and pathological conditions.
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Antígeno B7-H1 , Lesiones Traumáticas del Encéfalo , Humanos , Antígeno B7-H1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismo , Aprendizaje , Hipocampo/metabolismo , Anticuerpos Monoclonales/metabolismo , Neuronas/metabolismoRESUMEN
A 26-year-old woman with Ehlers-Danlos syndrome (EDS) underwent posterior spinal fusion with instrumentation for scoliosis. General anesthesia was maintained using propofol and remifentanil. The procedure was performed examining the motor evoked potential (MEP) and somatosensory evoked potential (SSEP) of the lower extremities with the patient placed in the prone position. The procedure was completed successfully without major cardiovascular or respiratory complications. The duration of anesthesia was 821 min. When drapes were removed, we noticed that the right shoulder was in a hyperabduction position. After emergence from anesthesia, it was observed that the right upper extremity was paralyzed. Thereafter, brachial plexus injury, which may have been due to intraoperative malpositioning, was diagnosed. Brachial plexus injury is the most common among the nerve injuries resulting from intraoperative malpositioning. Patients with EDS are thought to be at high risk for the complications and it has also been reported that patients with joint hypermobility, such as that in EDS or Marfan syndrome, are highly susceptible to nerve injury. Intraoperative monitoring of the MEP and SSEP in the upper extremities should be considered for early detection and prevention of brachial plexus injury in patients with EDS who are thought to be at high risk.
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Anestesia General , Plexo Braquial/lesiones , Síndrome de Ehlers-Danlos/complicaciones , Adulto , Femenino , Humanos , Complicaciones Intraoperatorias , Posición Prona , Escoliosis/cirugíaRESUMEN
BACKGROUND: Intraoperative nausea and vomiting (IONV) is a common symptom during cesarean section (CS) delivery causing significant discomfort to patients. Combined spinal and epidural anesthesia (CSEA) can provide both intraoperative anesthesia and postoperative analgesia. During CSEA, it is reasonable to administer local anesthetics to the epidural space before patient complaints to compensate for the diminished effect of spinal anesthesia. Therefore, we hypothesized that intraoperative epidural administration of 2% mepivacaine would reduce the incidence of IONV. METHODS: Patients who were scheduled for elective CS were randomly allocated to 2 groups. Patients and all clinical staff except for an attending anesthesiologist were blinded to the allocation. After the epidural catheter was inserted at the T11-12 or T12-L1 interspace, spinal anesthesia was performed at the L2-3 or L3-4 interspace to intrathecally administer 10 mg of 0.5% hyperbaric bupivacaine. Twenty min after spinal anesthesia, either 5 mL of 2% mepivacaine (group M) or saline (group S) was administered through an epidural catheter. Vasopressors were administered prophylactically to keep both the systolic blood pressure ≥ 80 % of the baseline value with the absolute value ≥ 90 mm Hg and the mean blood pressure ≥ 60 mm Hg. The primary endpoint was the incidence of IONV. The secondary endpoints were degree of nausea, the degree and incidence of pain, and Bromage score. RESULTS: Ninety patients were randomized, and 3 patients were excluded from the final analysis. There was no significant difference in the incidence of IONV between the groups (58% in group M and 61% in group S, respectively, P = .82). In contrast, the incidence and degree of intraoperative pain in group M were significantly lower compared to group S. In addition, the incidence of rescue epidural administration of fentanyl (18% vs 47%) or mepivacaine (2.3% vs 25%) for intraoperative pain was lower in group M compared to group S. CONCLUSIONS: Our results indicate that epidural administration of 2% mepivacaine 20 minutes after spinal anesthesia does not reduce the incidence of IONV in CS under CSEA. However, intraoperative epidural administration of 2% mepivacaine was found to improve intraoperative pain.
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Anestesia Obstétrica , Anestesia Raquidea , Anestesia Obstétrica/métodos , Anestesia Raquidea/efectos adversos , Anestesia Raquidea/métodos , Cesárea/efectos adversos , Cesárea/métodos , Espacio Epidural , Femenino , Humanos , Mepivacaína , Náusea/etiología , Náusea/prevención & control , Dolor , Embarazo , Estudios Prospectivos , VómitosRESUMEN
Chronic pain remains challenging to treat, despite numerous reports of its pathogenesis, including neuronal plasticity in the spinal dorsal horn (SDH). We hypothesized that understanding plasticity only at a specific time point after peripheral nerve injury (PNI) is insufficient to solve chronic pain. Here, we analyzed the temporal changes in synaptic transmission and astrocyte-neuron interactions in SDH after PNI. We found that synaptic transmission in the SDH after PNI changed in a time-dependent manner, which was accompanied by astrocyte proliferation and loss of inhibitory and excitatory neurons. Furthermore, neuronal loss was accompanied by necroptosis. Short-term inhibition of astrocytes after PNI suppressed these physiological and morphological changes and long-term pain-related behaviors. These results are the first to demonstrate that the inhibition of astrocyte proliferation after PNI contributes to the long-term regulation of plasticity and of necroptosis development in the SDH.
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BACKGROUND: Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes. METHODS: Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.9% saline. After recording baseline TCE-MEPs, the test drug was administered, following which TCE-MEP recordings were carried out every 2 minutes for up to 10 minutes. The primary outcome was the minimum relative TCE-MEP amplitude (peak-to-peak amplitude, percentage of baseline value) recorded in the left tibialis anterior muscle. Secondary outcomes included minimum relative MEP amplitudes recorded from all other muscle groups monitored in the study. Data are expressed as medians (interquartile range). RESULTS: The TCE-MEP amplitude of the left tibialis anterior muscle was significantly reduced following droperidol administration compared with saline (37% [30% to 55%] vs. 76% [58% to 93%], respectively, P <0.01). In the other muscles, the amplitudes were reduced in the droperidol group, except for the bilateral abductor pollicis brevis and the left quadriceps femoris muscles. The relative amplitude of the bilateral F waves recorded from the gastrocnemius was decreased in the droperidol group. CONCLUSIONS: Low-dose droperidol (20 µg/kg) reduced TCE-MEP amplitudes. Anesthesiologists should pay attention to the timing of droperidol administration during intraoperative TCE-MEP recordings, even if used in a low dose.
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Droperidol , Monitoreo Intraoperatorio , Adolescente , Adulto , Niño , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Músculo Esquelético/fisiología , Adulto JovenRESUMEN
BACKGROUND: A low-dose bolus or infusion of ketamine does not affect transcranial electrical motor-evoked potential (MEP) amplitude, but a dose ≥1 mg/kg may reduce MEP amplitude. We conducted a randomized, double-blinded, placebo-controlled study to evaluate the effect of ketamine (1 mg/kg) on transcranial electrical MEP. METHODS: Twenty female patients (aged 12 to 18 y) with adolescent idiopathic scoliosis scheduled to undergo posterior spinal fusion were randomly allocated to receive ketamine or saline. General anesthesia was induced and maintained with continuous infusions of propofol and remifentanil. MEP was elicited by supramaximal transcranial electrical stimulation. MEP recordings were obtained at baseline and then at 2, 4, 6, 8, and 10 minutes after administration of ketamine (1 mg/kg) or saline (0.1 ml/kg). The primary endpoint was the minimum relative MEP amplitude (peak-to-peak amplitude, % of baseline value) recorded from the left tibialis anterior muscle. The baseline amplitude recorded before test drug administration was defined as 100%. RESULTS: Medians (interquartile range) minimum MEP amplitudes in the left tibialis anterior muscle in the ketamine and saline groups were 26% (9% to 34%) and 87% (55% to 103%) of the baseline value, respectively (P<0.001). MEP amplitudes in other muscles were significantly reduced by ketamine. The suppressive effect of ketamine lasted for at least 10 minutes in each muscle. CONCLUSION: A 1-mg/kg bolus dose of ketamine can reduce MEP amplitude. Anesthesiologists should consider the dosage and timing of intravenous ketamine administration during MEP monitoring.
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Ketamina , Propofol , Escoliosis , Adolescente , Potenciales Evocados Motores , Femenino , Humanos , RemifentaniloRESUMEN
Opioid usage for pain therapy is limited by its undesirable clinical effects, including paradoxical hyperalgesia, also known as opioid-induced hyperalgesia (OIH). However, the mechanisms associated with the development and maintenance of OIH remain unclear. Here, we investigated the effect of serotonin inhibition by the 5-HT3 receptor antagonist, ondansetron (OND), as well as serotonin deprivation via its synthesis inhibitor para-chlorophenylalanine, on mouse OIH models, with particular focus on astrocyte activation. Co-administering of OND and morphine, in combination with serotonin depletion, inhibited mechanical hyperalgesia and astrocyte activation in the spinal dorsal horn of mouse OIH models. Although previous studies have suggested that activation of astrocytes in the spinal dorsal horn is essential for the development and maintenance of OIH, herein, treatment with carbenoxolone (CBX), a gap junction inhibitor that suppresses astrocyte activation, did not ameliorate mechanical hyperalgesia in mouse OIH models. These results indicate that serotonin in the spinal dorsal horn, and activation of the 5-HT3 receptor play essential roles in OIH induced by chronic morphine, while astrocyte activation in the spinal dorsal horn serves as a secondary effect of OIH. Our findings further suggest that serotonergic regulation in the spinal dorsal horn may be a therapeutic target of OIH. PERSPECTIVE: The current study revealed that the descending serotonergic pain-facilitatory system in the spinal dorsal horn is crucial in OIH, and that activation of astrocytes is a secondary phenotype of OIH. Our study offers new therapeutic targets for OIH and may help reduce inappropriate opioid use.