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BACKGROUND: Glycogen synthase kinase-3ß (GSK3ß), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect in cerebral ischemia-reperfusion (I/R) injury. METHODS: The function of the cerebral cortex in the mouse middle cerebral artery occlusion (MCAO) model (each group n = 6) and P12 cells oxygen-glucose deprivation/reoxygenation (OGD/R) model was analyzed using short hairpin GSK3ß lentivirus and overexpression of FTO lentivirus (in vitro), TLR4 inhibitor (TAK242), and LiCl to regulate GSK3ß, FTO, TLR4 expression, and GSK3ß activity, respectively. RESULTS: After GSK3ß knockdown in the OGD/R model of PC12 cells, the levels of TLR4 and p-p65 were lower than in the control, and the level of FTO was higher than in the control. Knockdown GSK3ß reversed the OGD/R-induced nuclear factor kappa-B transfer to the intranuclear nuclei. As indicated by the result, TLR4 expression was down-regulated by overexpressed FTO, and TLR4 expression was up-regulated notably after inhibition of FTO with the use of R-2HG. After the inhibition of the activity of GSK3ß in vivo, the reduction of FTO in mice suffering from MCAO was reversed. CONCLUSIONS: Our research shows that GSK3ß/FTO/TLR4 pathway contributes to cerebral I/R injury.
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PURPOSE: To determine the characteristics of the acute pain after laparoscopic-assisted vaginal hysterectomy (LAVH), laparoscopic myomectomy (LM), and laparoscopic adnexectomy (LA) and compare them with each other. PATIENTS AND METHODS: Patients undergoing LAVH, LM, and LA under general anaesthesia at the First Affiliated Hospital of Wenzhou Medical University between December 2017 and December 2019 were selected. Their data were collected before, during, and after the surgery. We evaluated the degrees of pain in each group of patients and compared them. RESULTS: There were differences in the baseline characteristics of the patients in the LAVH, LM, and LA groups. The severity and incidence of postoperative pain were higher in the LAVH group than in the LM and LA groups, followed by the LM and LA groups. Compared with the LA group, the postoperative pain in the LAVH and LM groups was more complicated. The LA group had the lowest incidence of two or more types of moderate to severe pain. The LAVH and LM groups mainly had visceral pain and low back pain, and the LA group mainly had incisional pain. Shoulder pain had the lowest incidence in the three groups. CONCLUSION: There were different postoperative pain characteristics after the LAVH, LM, and LA, and we should clinically adjust analgesia programs for different gynaecological laparoscopic surgeries.
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INTRODUCTION: The aim of the study was to study the role of the anterior cingulate cortex (ACC)-dorsal midbrain striatum (DMS) in neuropathic pain in mice. MATERIAL AND METHODS: Optogenetics has been increasingly used in neuroscience research to selectively and precisely control the activity of a defined group of central neurons to determine their roles in behavioral functions in animals. The most important opsins are blue-sensitive ChR2 and yellow-sensitive NpHR. Calcium-calmodulin dependent protein kinase Iiα (CaMKIIα) is mostly expressed in the pyramidal excitatory neurons. Mice were injected with AAV2/9-CamKII-ChR2-mCherry, AAV2/9-CamKII-eNpHR3.0-GFP or AAV2/9-CamKII-mCherry virus in the ACC region, and the optical fiber implantation was performed in the ACC or DMS region. Mice were then followed up for 2 to 8 weeks and behavioral tests were carried out in the presence or absence of the blue/yellow light (473 nm/589 nm). Pain behavioral tests with or without the blue/yellow light at the same time were performed on the third and the seventh day after the chronic constriction injury of sciatic nerve model (CCI) was established. The pain thresholds of left and right hind limbs of mice in all groups were measured. RESULTS: No matter whether activating the neurons in ACC or DMS, compared with normal mice in the ChR2-off-right group, and the mCherry-on-right group, the thermal pain threshold and mechanical pain threshold of the normal mice in the ChR2-on-right group were significantly lower. When inhibiting the neurons in the ACC or DMS, on day 3 and day 7 after CCI operation, the thermal pain threshold and mechanical pain threshold of the CCI mice of the NpHR-on-right group were significantly higher compared with the NpHR-off-right and mCherry-on-right groups. CONCLUSIONS: The anterior cingulate cortex-dorsal midbrain striatum may be involved in the regulation of neuropathic pain in mice.
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A previous study has demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. In the present study, we investigated whether adenosine receptor 1 (A1 R) is involved in EA pretreatment-induced cognitive impairment after focal cerebral ischemia in rats. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min in male Sprague-Dawley rats. The neurobehavioral score, cognitive function [as determined by the Morris water maze (MWM) test], neuronal number, and the Bax/Bcl-2 ratio was evaluated at 24 h after reperfusion in the presence or absence of CCPA (a selective A1 receptor agonist), DPCPX (a selective A1 receptor antagonist) into left lateral ventricle, or A1 short interfering RNA into the hippocampus area. The expression of the A1 receptor in the hippocampus was also investigated. The result showed that EA pretreatment upregulated the neuronal expression of the A1 receptor in the rat hippocampus at 90 min. And EA pretreatment reversed cognitive impairment, improved neurological outcome, and inhibited apoptosis at 24 h after reperfusion. Pretreatment with CCPA could imitate the beneficial effects of EA pretreatment. But the EA pretreatment effects were abolished by DPCPX. Furthermore, A1 receptor protein was reduced by A1 short interfering RNA which attenuated EA pretreatment-induced cognitive impairment.
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OBJECTIVE: To explore the efficacy difference between electroacupuncture (EA) at "Zusanli" (ST36) and "Baihui" (GV20) for inflammatory pain and cerebral ischemia-reperfusion injury (CIRI) in rats. METHODS: In 1st part of this study, 90 male SD rats were randomly divided into sham-operation, model (induced by occlusion of the middle cerebral artery and reperfusion), GV20 EA, ST36 EAï¼and sham EA groups (n=16 in each group). In the 2nd part of the study, 40 male SD rats were randomized into saline injection (control), inflammatory pain model (subcutaneous injection of complete Freund's adjuvant ï¼»CFAï¼½ into the right paw), ST36 EA, GV20 EA, and sham EA groups (n=8 in each group). In these two parts, EA (2 Hz/15 Hz, 1 mA) was applied to ST36 or GV20. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency ï¼TWLï¼ were detected 2.5 h after administration of CFA by using Von Frey and plantar tester, respectively. The neurological deficit scores (NDS) were assessed by using Longa's method and the infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride (TTC). The expression of c-fos protein in the dorsal horns (DHs) of the spinal cord was detected by immunohistochemistry. RESULTS: (1) Twenty-four hours following CIRI, the NDS and infarct volume were significantly increased in the model group compared with the sham-operation group (P<0.01), and obviously decreased in the GV20 EA and ST36 EA groups relevant to the CIRI model group (P<0.05, P<0.01). There were no significant differences between the two EA groups in the NDS and infarct volume levels (P>0.05). (2) After administration of CFA, both the MPT and TPT were notably decreased in the inflammatory pain model group in contrast to the saline-injection group (P<0.01), but were considerably increased in both ST36 EA and GV20 EA groups (P<0.05), rather than in the sham EA group (P>0.05). The number of c-fos positive cells was significantly increased in the medial half of I-II and III-IV lamina of DHs in the L4-L6 segments of spinal cord in the inflammatory pain model group relevant to the saline-injection group (P<0.01,P<0.05), and was remarkably decreased in the lamina I-II (not in the deeper lamina) in both ST36 EA and GV20 EA groups (P<0.01), rather than in the sham EA group (P>0.05). No significant differences were found in the number of c-fos positive cells between the ST36 EA and GV20 EA groups (P>0.05). CONCLUSION: Our data do not support the specificity of functions at least between GV20 EA and ST36 EA in both CIRI and inflammatory pain model rats. This is the first study reporting the effect of EA at GV20 for relieving CFA-induced inflammatory pain.
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Isquemia Encefálica , Electroacupuntura , Daño por Reperfusión , Animales , Isquemia Encefálica/terapia , Masculino , Dolor/etiología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/terapiaRESUMEN
OBJECTIVE: To investigate the effect of transcutaneous electrical acupoint stimulation (TEAS) on pulmonary function, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in patients using tourniquet after lower extremity surgery. METHODS: A total of 40 patients who underwent lower extremity surgery were equally randomized into control group and TEAS group by using a random number table. All patients underwent lumbar epidural anesthesia combined with block anesthesia. The patients in the TEAS group were given TEAS at Zusanli (ST36) and Sanyinjiao (SP6) beginning from 30 min before surgery to the end of surgery, and those in the control group received TEAS at the same acupoints with minimum current intensity. Mean arterial pressure (MAP) and heart rate (HR) were recorded at each time point (T0: pre-surgery /TEAS, T1: 5 min after anesthesia, T2: 1 min before tourniquet-loosening, T3: 1 min after tourniquet-loosening, T4: 5 min after tourniquet-loosening, and T5: 6 h after tourniquet-loosening). Blood samples (4 mL) was collected from the radial artery before TEAS and 6 h after loosening tourniquet for analyzing blood gas parameters as partial pressure of caron dioxide(PCO2), arterial partial pressure of oxygen (PaO2), alveolar partial pressure of oxygen (PAO2), alveolar-arterial oxygen pressure difference (PA-aDO2) and respiratory index (RI) by using a blood gas analyzer, and plasma SOD activity and MDA content were assayed by using xanthine oxidase method and thiobarbituric acid colorimetry method, respectively. RESULTS: Intra-group comparison showed that compared with T0, a significant increase was found in PA-aDO2 and RI at T5 and a significant reduction in PaO2 and PaO2/ PAO2 (a/A) ratio in the control group (P<0.05), and the same changes in the TEAS group (P<0.05) except a/A ratio. Comparison between two groups showed that at T5, both PaO2 and a/A levels were significantly higher in the TEAS group than in the control group (P<0.05), and both PA-aDO2 and RI levels were obviously lower in the TEAS group than in the control group (P<0.05), suggesting an improvement of the pulmonary function after TEAS. At T5, plasma SOD activity was significantly decreased and plasma MDA content was remarkably increased in the control group relevant to T0 (P<0.05), SOD activity was significantly higher in the TEAS group than in the control group (P<0.05), and MDA content was evidently lower in the TEAS group than in the control group (P<0.05), suggesting a reduction of oxidative stress response after TEAS. CONCLUSION: TEAS at ST36 and SP6 can improve pulmonary function and attenuate oxidative stress response in patients using tourniquet after lower extremity surgery.
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Puntos de Acupuntura , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Extremidad Inferior , Estrés Oxidativo , TorniquetesRESUMEN
Electroacupuncture (EA) is widely used in clinical settings to reduce inflammatory pain. Islet-cell autoantigen 69 (ICA69) has been reported to regulate long-lasting hyperalgesia in mice. ICA69 knockout led to reduced protein interacting with C-kinase 1 (PICK1) expression and increased glutamate receptor subunit 2 (GluR2) phosphorylation at Ser880 in spinal dorsal horn. In this study, we evaluated the role of ICA69 in the antihyperalgesic effects of EA and the underlying mechanism through regulation of GluR2 and PICK1 in spinal dorsal horn. Hyperalgesia was induced in mice with subcutaneous plantar injection of complete Freund adjuvant (CFA) to cause inflammatory pain. Electroacupuncture was then applied for 30 minutes every other day after CFA injection. When compared with CFA group, paw withdrawal frequency of CFA+EA group was significantly decreased. Remarkable increases in Ica1 mRNA expression and ICA69 protein levels on the ipsilateral side were detected in the CFA+EA group. ICA69 expression reached the peak value around day 3. More importantly, ICA69 deletion impaired the antihyperalgesic effects of EA on GluR2-p, but PICK1 deletion could not. Injecting ICA69 peptide into the intrathecal space of ICA69-knockout mice mimicked the effects of EA analgesic and inhibited GluR2-p. Electroacupuncture had no effects on the total protein of PICK1 and GluR2. And, EA could increase the formation of ICA69-PICK1 complexes and decrease the amount of PICK1-GluR2 complexes. Our findings indicate that ICA69 mediates the antihyperalgesic effects of EA on CFA-induced inflammatory pain by regulating spinal GluR2 through PICK1 in mice.
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Autoantígenos/metabolismo , Proteínas Portadoras/metabolismo , Electroacupuntura/métodos , Regulación de la Expresión Génica/genética , Proteínas Nucleares/metabolismo , Receptores AMPA/metabolismo , Médula Espinal/metabolismo , Animales , Autoantígenos/química , Autoantígenos/genética , Autoantígenos/uso terapéutico , Proteínas Portadoras/genética , Proteínas de Ciclo Celular , Modelos Animales de Enfermedad , Adyuvante de Freund/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Inmunoprecipitación , Inflamación/inducido químicamente , Inflamación/complicaciones , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Nucleares/genética , Dolor/complicaciones , Dolor/etiología , Manejo del Dolor , Fosforilación/fisiología , ARN Mensajero/metabolismo , Factores de TiempoRESUMEN
Background/aim: This study aimed to study the effect of pretreatment transcutaneous electrical acupoint stimulation (TEAS) in preventing propofol injection-related pain. Materials and methods: A total of 360 patients who were to undergo elective hysteroscopy surgery were randomly divided into the following three groups of 120 patients each: control (Group C), sham TEAS (Group F), and TEAS (Group T). Patients in Group C did not undergo any treatment before surgery; 30 min before the induction of anesthesia, patients in Groups F and T underwent electrical stimulation of the bilateral LI4-PC6 acupoint. Patients in Group F were subjected to 'feeling flow', while those in Group T were subjected to 'tolerance flow.' The stimulation frequency was 2/100 Hz and the duration of stimulation was 30 min. After the induction of anesthesia, propofol injection-related pain scores, hemodynamic parameters, and adverse reactions were recorded. Results: Of the 360 patients, 324 completed the study. There were significant differences among the groups in terms of the incidence of moderate-to-severe pain. In terms of the four-point scaling method, the end of the radial vein, the cubital vein, and the 'back of the hand' vein differed significantly among the three groups (P = 0.05). Finally, using a numerical rating scale, a significant difference was observed among the three groups in terms of the pain scores in the different veins. Conclusions: Pretreatment TEAS effectively reduces the incidence and severity of propofol injection-related pain, the incidence of postoperative nausea and vomiting, and patient postoperative pain scores.
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The activation of adenosine A1 receptors is important for protecting against ischemic brain injury and pretreatment with electroacupuncture has been shown to mitigate ischemic brain insult. The aim of this study was to test whether the adenosine A1 receptor mediates electroacupuncture pretreatment-induced neuroprotection against ischemic brain injury. We first performed 30 minutes of electroacupuncture pretreatment at the Baihui acupoint (GV20), delivered with a current of 1 mA, a frequency of 2/15 Hz, and a depth of 1 mm. High-performance liquid chromatography found that adenosine triphosphate and adenosine levels peaked in the cerebral cortex at 15 minutes and 120 minutes after electroacupuncture pretreatment, respectively. We further examined the effect of 15 or 120 minutes electroacupuncture treatment on ischemic brain injury in a rat middle cerebral artery-occlusion model. We found that at 24 hours reperfusion,120 minutes after electroacupuncture pretreatment, but not for 15 minutes, significantly reduced behavioral deficits and infarct volumes. Last, we demonstrated that the protective effect gained by 120 minutes after electroacupuncture treatment before ischemic injury was abolished by pretreatment with the A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 mg/kg, intraperitoneally). Our results suggest that pretreatment with electroacupuncture at the Baihui acupoint elicits protection against transient cerebral ischemia via action at adenosine A1 receptors.
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Previous studies have demonstrated that pretreatment with electroacupuncture (EA) elicits rapid tolerance to focal cerebral ischemia and that Wnt/ß-catenin plays an essential role in cell survival and proliferation. In the present study, we investigated the role of Wnt/ß-catenin in EA pretreatment-induced neuroprotection. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h. Neuronal survival, cell apoptosis, and the Garcia neurological deficit scores were evaluated 24 h after reperfusion. Moreover, learning and memory deficits were assessed 24 h after reperfusion using the Morris water maze test. Finally, the expression of ß-catenin and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were investigated in the presence and absence of the Wnt/ß-catenin antagonist Dickkopf-1 (Dkk-1), which was administered 30 min before MCAO. We observed that EA pretreatment significantly increased the neuronal expression of ß-catenin in the hippocampus 24 h after reperfusion. Moreover, EA pretreatment improved the neurological outcomes, decreased neuronal loss, inhibited apoptosis, and reversed learning and memory deficits following reperfusion. These beneficial effects of EA were attenuated by Dkk-1, which effectively reversed the expression of ß-catenin. Furthermore, the administration of a Wnt/ß-catenin agonist upregulated the expression of ß-catenin and the Bcl-2/Bax ratio. These results suggest that Wnt/ß-catenin plays a role in the protective effects of EA pretreatment against cerebral ischemia, thus providing evidence of a novel mechanism underlying EA-pretreatment-induced rapid tolerance to focal cerebral ischemia.