Effects of acupuncture on regulating the hippocampal inflammatory response in rats exposed to post-traumatic stress disorder.

Data from clinical and experimental studies have verified the efficacy and safety of acupuncture in the treatment of post-traumatic stress disorder (PTSD). However, the concrete mechanism has not been well elucidated. The stress-induced activation of inflammatory response is involved in the development and pathogenesis of PTSD. Here, we aimed to investigate the effects of acupuncture on regulating the hippocampal inflammatory response in rats exposed to PTSD. Forty male rats were randomly divided into control, model, acupuncture and sertraline group. Within 1 day after adaptive feeding, all rats were exposed to single prolonged stress (SPS), except for the rats in the control group. Rats in acupuncture group were exposed to acupuncture intervention at the acupoints of Baihui (GV20) and Yintang (GV29), 20 min once per day for 15 days. Rats in sertraline group were exposed to a suspension of sertraline and distilled water (0.2 mg/ml), once per day for 15 days continuously. Body weight and elevated plus maze experiment were detected at different time-points to evaluate the behavioral changes of rats. HE staining method was used to observe the basic pathological morphological changes in hippocampus. Immunofluorescence staining method was used to observe the activation of hippocampal microglia. The content of IL-6 and IL-1ß in serum were detected by ELISA method. Compared with the control group, the body weight of rats in model group significantly decreased on 8 days, and the percentage of time in open arms and open arm entries decreased significantly on 15 days after SPS procedures, which indicated that SPS induced PTSD-like behavior in rats. Acupuncture exerted therapeutic effect. Simultaneously, the result of HE staining confirmed that SPS induced hippocampal morphological changes in SPS rats. Notably, acupuncture reversed the reduction and pathological injury to some extent. The results have also shown that acupuncture intervention effectively reversed the activated microglia of the hippocampus in rats. Moreover, the expression of IL-1ß in serum was significantly decreased by acupuncture intervention. In summary, the present study demonstrated that the role of acupuncture in eliminating PTSD-like behavior might be connected with reversing the pathological process of the inflammatory response mediated by the activation of microglia induced by SPS.

Acupuncture Ameliorates Depressive Behaviors by Modulating the Expression of Hippocampal Iba-1 and HMGB1 in Rats Exposed to Chronic Restraint Stress.

The antidepressant mechanism of acupuncture has not been fully elucidated recently. Thus, the objective of the present study is to investigate the antidepressant mechanism of acupuncture of modulating the neuroinflammation induced by high mobility group box-1 (HMGB1) in rats subjected to chronic restraint stress (CRS). Forty-four male Sprague Dawley rats were randomly divided into control, model, escitalopram, and acupuncture group. Except for rats in the control group, all rats were exposed to CRS for 21 days continuously. Rats in the escitalopram group were subjected to a suspension of escitalopram and saline. One hour before CRS procedures, acupuncture was performed at Baihui (GV20) and Yintang (GV29) for rats in the acupuncture group, 20 min per day for 21 days. All rats in each group were conducted to detect the body weight, sucrose preference test at 0, 7, 14, 21 days to evaluate the depression-like behaviors. The expression of microglial activation and HMGB1 in the hippocampus was detected by immunofluorescence. The expression of hippocampal interleukin-10 (IL-10) was detected by western blot. And the content of serum tumor necrosis factor-α (TNF-α) was detected by the enzyme-linked immunosorbent assay method. CRS-exposed rats showed obviously decreased body weight and sucrose preference when compared with the control group, which was reversed by acupuncture. The results have also shown that acupuncture ameliorated the CRS-induced activation of microglia and HMGB1 in the hippocampus CA1 region. Furthermore, acupuncture reduced the stress-induced upregulation of TNF-α in serum. Collectively, the current study highlights the role of acupuncture in alleviating depressive behavior associated with stress-induced neuroinflammation mediated by HMGB1 in the CRS model of depression.

Effect of electroacupuncture on glial fibrillary acidic protein and nerve growth factor in the hippocampus of rats with hyperlipidemia and middle cerebral artery thrombus.

Electroacupuncture (EA) has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia. However, there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects. In this study, EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed. Except for the normal group, rats in other groups were fed a high-fat diet throughout the whole experiment. Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks. Middle cerebral artery thrombus models were induced by pasting 50% FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group. EA1 group rats received EA at bilateral ST40 (Fenglong) for 7 days before the thrombosis. Rats in the EA1 and EA2 groups received EA at GV20 (Baihui) and bilateral ST40 for 14 days after model establishment. Neuronal health was assessed by hematoxylin-eosin staining in the brain. Hyperlipidemia was assessed by biochemical methods that measured total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein in blood sera. Behavioral analysis was used to confirm the establishment of the model. Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region. The results demonstrated that, compared with the model group, blood lipid levels significantly decreased, glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups. The repair effect was superior in the EA1 group than in the EA2 group. These findings confirm that EA can reduce blood lipid, inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis. All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine, China (approval No. BUCM-3-2018022802-1002) on April 12, 2018.

Ionic liquid functionalized ß-cyclodextrin and C18 mixed-mode stationary phase with achiral and chiral separation functions.

A novel reversed-phase/hydrophilic interaction/ion-exchange (RPLC/HILIC/IEC) and chiral recognition mixed-mode stationary phase material was synthesized using 3-n-octadecyl-1-vinylimidazolium bromide and 6-(1-allylimidazolium)-cyclodextrin tosylate as functional monomers. After identifications of intermediates and stationary phase materials using nuclear magnetic resonance analysis, Fourier transform infrared spectrometer, element analysis and thermogravimetric analysis, the synthesized Sil-VMBD material was packed into an empty column under high pressure. The mixed-mode retention performance was researched by hydrophobic, hydrophilic and ionic compounds. And the retention mechanism of the multi-mode stationary phase was studied via changing the mobile phase composition and pH value. Moreover, the enantiomers of 1-phenyl-1-propanol, warfarin and styrene oxide were separated rapidly under reverse-phase mode. Fast enantioseparation of ibuprofen and ketoprofen were obtained within 4 min under polar organic mode. The experimental results show that the as-prepared mixed-mode column possesses reversed-phase, hydrophilic and ion-exchange interactions with various analytes, and these interactions also enable the stationary phase with multi-mode and chiral separation abilities.

Preparation of an aminophenylboronic acid and N-isopropyl acrylamide copolymer functionalized stationary phase for mixed-mode chromatography.

A novel stationary phase co-modified with N-isopropyl acrylamide (NIPAM) and 3-aminophenylboronic acid copolymer on the silica was synthesized through atom transfer radical polymerization (ATRP) reaction for performing mixed-mode and boronate affinity chromatography. The prepared functionalized silica was characterized using Fourier transform infrared spectrometry (FT-IR), elemental analysis (EA) and thermogravimetric analysis (TGA), scanning electron micrographs (SEM) and Brunauer-Emmett-Teller (BET) measurements. The prepared column named Sil-PBA-NIPAM showed great separation performance for hydrophobic, hydrophilic, positional isomer, acidic and alkaline compounds. Besides, the mixture of cis-diol and non-cis-diol compounds was used to prove that the developed column also has potential to capture and enrich cis-diol compounds. The prepared column possesses merits of time-saving, high selectivity to cis-diol compounds and molecular-planarity selectivity compared with two commercial single-mode columns. The theoretical plates of material can reach to 57472 and the column has good hydrolysis stability and batch-to-batch reproducibility. In summary, the prepared column possesses good hydrophilicity, hydrophobicity, molecular-planarity selectivity and boronate affinity abilities for the analysis of various compounds.

Thermoresponsive chiral stationary phase functionalized with the copolymer of ß-cyclodextrin and N-isopropylacrylamide for high performance liquid chromatography.

A novel chiral stationary phase (CSP) was prepared through the reaction of surface-initiated atom transfer radical polymerization (ATRP) by the copolymerization of thermoresponsive N-isopropylacrylamide (NIPAM) and ß-cyclodextrin (ß-CD) on the silica beads for high performance liquid chromatography (HPLC). X-ray photoelectron spectroscopy (XPS), elemental analysis (EA), Fourier transform infrared spectrometry (FT-IR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) were applied to characterize the surface property of modified silica. Thermoresponsive modulation for the effect on enantioselectivity were investigated with chiral reagents including 1-phenyl-1-propanol, styrene oxide, 2-phenylpropionic acid and commercial chiral drugs comprising ibuprofen and labetalol hydrochloride. The column efficiency was evaluated by chromatographic parameters including retention factor (k), selective factor (α), resolution (Rs), plate number (N) and peak tailing factor (Tf). The results showed that five chiral solutes could be separated on the prepared smart column. And the selectivity of these compounds could be modulated by regulating the column temperature. It was contributed to the thermoresponsive NIPAM assisting ß-CD to separate these chiral compounds. These results indicated that the thermoresponsive CSP would be a potential tool for separation of hydrophilic and hydrophobic chiral drugs and this paper provided a novel method for chiral separation in the future.

Preparation and evaluation of a molybdenum disulfide quantum dots embedded C18 mixed-mode chromatographic stationary phase.

Molybdenum disulfide quantum dots (MoS2 QDs) were chosen as a functional two-dimensional material to improve the separation performance of a traditional C18 column. In this work, MoS2 QDs were synthesized by the combination of sonication and solvothermal treatment of bulk MoS2. The prepared MoS2 QDs were characterized by transmission electron microscope (TEM), Zeta potential measurement, UV-visible absorption and fluorescence spectroscopy. Then, a novel MoS2 QDs embedded C18 (Sil-MoS2-C18) stationary phase was prepared for performing mixed-mode liquid chromatography. The results of elemental analysis (EA), thermogravimetric analysis (TGA), Fourier transform infrared spectrometry (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and Brunauer-Emmett-Teller (BET) measurements indicated the stationary phase was prepared successfully. Five types of compounds including alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs), nucleosides and nucleobases, anilines and flavonoids were utilized to evaluate reversed phase, weak cation exchange and hydrophilic interaction of the new column. To a certain extent, the column could achieve separation for different properties of samples on one column, with less organic solvent and shorter time than conventional alkyl and amino columns. Furthermore, the mechanism for separation was studied by investigating effects of mobile phase composition and pH on retentions. In summary, the Sil-MoS2-C18 stationary phase was deemed able to serve the performance of various types of phases, which revealed the prepared mixed-mode column could be potentially applied for the analysis of complex samples. Graphical abstract.

Preparation of a poly(ethyleneimine) embedded phenyl stationary phase for mixed-mode liquid chromatography.

A poly(ethyleneimine) embedded phenyl mixed-mode stationary phase was prepared through epoxide ring opening reaction. Elemental analysis (EA), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) were used to characterize whether functional groups have been modified on the surface of silica successfully. The researches of chromatographic performance for designed column were divided to four parts. The retention behavior under reversed-phase mode was studied using polycyclic aromatic hydrocarbons (PAHs), positional isomers and alkylbenzenes. The retention characteristic under hydrophilic interaction mode was studied by nucleosides, nucleobases and flavonoids. The chromatographic performance of anion exchange mode was evaluated by benzoic acids and phenols. Due to a high content of amino and phenyl groups on the stationary phase, aromatic amines were chosen for the evaluation of retention mechanisms of benzene ring attraction and amino repulsion. The investigations about effects of mobile phase constitution and pH on retention demonstrated the mixed-mode retention mechanisms of the column. Furthermore, due to amino selectivity of the column, a method for the rapid separation and determination of phenylenediamines in hair dye was established. And both linear correlation coefficients of p-diaminobenzene and m-diaminobenzene in concentration range from 0.1 to 30 µg mL-1 were over 0.999. In conclude, the prepared mixed-mode stationary phase could realize various separation modes by adjusting chromatographic conditions, and it had the potential for the rapid separation and determination of aniline compounds in various complex samples.

Preparation and evaluation of a reversed-phase/hydrophilic interaction/ion-exchange mixed-mode chromatographic stationary phase functionalized with dopamine-based dendrimers.

In this work, a novel dendritic stationary phase was synthesized by the repeated grafting of 1,4-butanediol diglycidyl ether (BDDE) and dopamine (DA) on the surface of silica for performing mixed-mode high-performance liquid chromatography (MHPLC). Elemental analysis (EA), thermogravimetric analysis (TGA) and Fourier transform infrared spectrometry (FT-IR) showed the successful preparation of the dendritic stationary phase. The prepared stationary phase showed the retention mechanisms of reversed-phase liquid chromatography (RPLC), hydrophilic interaction chromatography (HILIC) and ion-exchange chromatography (IEC) under different mobile phase conditions. In detail, alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs) and hydrophobic positional isomers were separated successfully in the RPLC mode. The baseline separation of nucleobases, nucleosides and flavonoids was achieved under HILIC mode, respectively. Meanwhile, some acidic and basic analytes were used to evaluate the IEC mode. The effects of different chromatographic conditions, such as acetonitrile content, salt concentration and pH in the mobile phase, on the different chromatographic modes were also investigated. In addition, the application of the mixed-mode dendritic stationary phase was demonstrated by the analysis of traditional Chinese medicine (TCM), including Carthamus tinctorius L. and Abelmoschus manihot (Linn.) Medicus. Interestingly, the stationary phase also has the ability for the capture and separation of boric acids. These meaningful applications confirmed that the mixed-mode dendritic stationary phase can be potentially applied in the analysis of complex samples.

Mixed-mode liquid chromatography with a stationary phase co-functionalized with ionic liquid embedded C18 and an aryl sulfonate group.

A novel silica stationary phase was designed and prepared through thiol-ene click chemistry by functionalizing imidazolium based ionic liquid embedded C18 and an aryl sulfonate group for the mixed-mode liquid chromatography. The developed stationary phase was characterized by elemental analysis (EA), Fourier transform infrared spectrometry (FT-IR) and thermogravimetric analysis (TGA). The chromatographic performances of the prepared column were investigated by reversed phase chromatography using alkylbenzenes and positional isomers, hydrophilic interaction chromatography using nucleosides, nucleic bases and flavonoids, and ion exchange chromatography using acidic and basic analytes. The stationary phase showed faster separation and better performance for these compounds compared to the conventional alkyl stationary phase, especially for the separation of positional isomers. The investigations about water percentage and pH of the mobile phase for retentions provided information that the stationary phase offered multiple interactions with samples including hydrophobic, hydrophilic and electrostatic interactions. Moreover, improved separation efficiency of Qinghuozhimai tablet and vitamin B2 tablet were successfully achieved respectively on a single mixed-mode column. In conclusion, the multimodal retention capabilities of the developed stationary phase could offer flexible selectivity toward various types of compounds and complex samples.

[Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40), "Sanyinjiao" (SP 6) plus manual acupuncture (MA) stimulation of "Shuigou" (GV 26) and "Baihui" (GV 20) on Caspase-3 protein expression in the cerebral cortex of rats with hyperlipemia and cerebral ischemia(HL-CI),so as to reveal its mechanisms underlying improvement of HL-CI. METHODS: Forty-five rats were randomly divided into normal control,sham operation,model,EA group I(EA+MA was given for 14 days, i.e., 7 days before CI, and 7 days more after HL-CI)and EA group Ⅱ (EA+MA was given for only 7 days after HL-CI),with 9 rats being in each group. The HL-CI model was established by feeding the animals with high fat forage for 6 weeks and then making an occlusion of the unilateral middle cerebral artery by regional application of quantitative paper adsorbing 50% FeCl3 solution (10 µL). Rats of the sham operation group were treated with the same procedures only without application of FeCl3 solution. For rats of the EA group I,EA (1-3 mA, 2 Hz/100 Hz) was applied to bilateral acupoints SP 6 and ST 40 (for 20 min),and MA stimulation applied to GV 26 and GV 20. EA was conducted once daily for 7 days after 6 weeks' high fat fo-rage feeding, and EA+MA intervention was conducted once daily for 7 days after CI modeling. For rats in the EA group Ⅱ, EA+MA was applied to the same 4 acupoints once a day for 7 days only after CI modeling. The neurological impairment was assessed by Zea Longa's scoring. The blood sample was taken from the abdominal aorta for measuring the contents of serum cholesterol (CHO),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Pathological changes of the cerebral cortex were observed after H.E. staining, and the expression of cerebro-cortex Caspase-3 was analyzed by immunohistochemistry. RESULTS: Following modeling,the neurological score,CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells as well as Caspase-3 immunoactivity level were significantly increased in the model group(P<0.05), while serum HDL-C level was obviously decreased(P<0.05). After the treatment,the increased neurological score, CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells and Caspase-3 immunoactivity level were considerably decreased in the EA group I and Ⅱ(P<0.05)while the decreased HDL-C level was notably increased relevant to the model group(P<0.05). The effects of the EA group I were notably superior to those of EA group Ⅱ in down-regulating the neurological score,CHO, TG and LDL-C levels and the expression of Caspase-3 protein(P<0.05). No significant differences were found between the normal control and sham operation groups in the neurological scores 20 min and 7 days after modeling and Caspase-3 expression levels (P>0.05). H.E. staining showed a reduction of the apoptotic cells and inflammatory cells in both EA group I and Ⅱ. CONCLUSIONS: Both EA and EA+MA interventions can improve neurological function in HL-CI rats,which may be related to their effects in adjusting the levels of serum lipids and down-regulating the expression of cell apoptosis-related Caspase-3 protein in the ischemic cortex. Moreover, the cerebral ischemia injury may be lightened by EA-lowering hyperlipemia first.

Effect of electroacupuncture on E-prostanoid 2 expression in the spinal cord in rats with neuropathic pain.

OBJECTIVE: To observe the effect of electroacupuncture (EA) treatment on the expression of E-prostanoid 2 (EP2) in the spinal cord using a rat model of neuropathic pain, and to examine the effect of different acupuncture prescriptions. METHODS: Rats were randomly divided into six groups: a normal group, model group, sham group, EA 1 group (distal-proximal acupoints), EA 2 group (proximal acupoints), and EA 3 group (distal acupoints). Rats in the EA groups were treated for 20 min, once daily for 7 days. The mechanical withdrawal threshold was evaluated at 1 day preoperatively and at 3, 5, and 7 days postoperatively. At 7 days postoperatively, hematoxylin-eosin (HE) staining was used to investigate spinal morphological changes. Spinal EP2 messenger ribonucleic acid (mRNA) was detected using reverse-transcription polymerase chain reaction. RESULTS: After the EA treatment, the mechanical withdrawal threshold was up-regulated compared with the model group (P < 0.05). The expression of EP2 mRNA was up-regulated in the spinal cord on day 7 after surgery (P < 0.05). EA stimulation tended to down-regulate EP2 mRNA expression compared with the model group (P > 0.05). The EA 1 and EA 2 groups showed a larger treatment effect than the EA 3 group. The HE results showed that EA can improve spinal histomorphology induced by neuropathic pain. CONCLUSION: EA had a strong analgesic and anti-inflammatory effect. The therapeutic effect of EA on the down-regulation of spinal EP2 mRNA expression may be greater when either local acupoints or a distal-proximal combination of acupoints are used than when distal points are used.

Effects of electroacupuncture intervention on expression of cyclooxygenase 2 and microglia in spinal cord in rat model of neuropathic pain.

OBJECTIVE: To investigate the effect of electroacupuncture (EA) treatment on the expression of cyclooxygenase (COX) 2 and microglia in spinal cord by using rat model of neuropathic pain, and to probe into the relationship between COX 2 and microglia. METHODS: The rats were randomly divided into 6 groups, including normal control group, model group, sham group, EA 1 group (distant acupoints + local acupoints), EA 2 group (local acupoints), and EA 3 group (distant acupoints). Thermal withdrawal latencies were evaluated at 1 day preoperatively and 3, 5 and 7 days postoperatively. At 7 days postoperatively, the spinal COX 2 mRNA was detected by reverse-transcription polymerase chain reaction. Double immunofluorescent staining technology was applied to screen and verify the relationship between altered COX 2 and microglia. RESULTS: Compared with the model group, thermal withdrawal latencies increased after EA treatment (P<0.01). The expressions of COX 2 mRNA were up-regulated in spinal cord of rat on day 7 after surgery (P<0.05). Compared with the model group, EA stimulation (EA 1 and EA 2 groups) reversed the up-regulation of COX 2 mRNA expression (P<0.05). EA 1 and EA 2 groups might have better treatment effect compared with the EA 3 group. Fluorescent images displayed COX 2 and microglia expressed at common areas. CONCLUSIONS: EA was effective in analgesic and anti-inflammatory. EA has decreased the expression of spinal COX 2 mRNA in the trend of the therapeutic effect of "distant acupoints + local acupoints", and "local acupoints" intervention may be superior to that of "distant acupoints" intervention. Microglia may be related to the formation of COX 2.

Electroacupuncture alters pain-related behaviors and expression of spinal prostaglandin E2 in a rat model of neuropathic pain.

OBJECTIVE: To investigate the role of spinal prostaglandin E2 (PGE2) in electroacupuncture (EA) analgesia and assess the theoretical basis for selection of acupoints in the treatment of neuropathic pain. METHODS: A rat model of neuropathic pain was established. Rats were randomly divided into normal, model, sham, EA 1, EA 2, and EA 3 groups. In EA 1 group, the rats were needled at bilateral L5 Jiaji (EX-B2), Dachangshu (BL 25), Weizhong (BL 40) and Kunlun (BL 60). In EA 2 group, the rats were needled at bilateral Weizhong (BL 40) and Kunlun (BL 60). In EA 3 group, the rats were needled at bilateral L5 Jiaji (EX-B2) and Dachangshu (BL 25). EA stimulation was administered once daily over 7 days. Motor function and thermal withdrawal latencies were evaluated at 1 day preoperatively and at 3, 5, and 7 days postoperatively. After 7 days of intervention, enzyme-linked immunosorbnent assay (ELISA) was used to quantify the expression of the spinal PGE2. RESULTS: Rats in the model group exhibited evident hyperalgesia in responses to thermal withdrawal latencies compared with those in the control group (P < 0.01), and EA reversed thermal withdrawal latencies (P < 0.01). The expression level of the spinal PGE2 was significantly higher in the model group than that in the control group and was reversed by EA (P < 0.01; P < 0.05). CONCLUSION: The effect of EA on neuropathic pain might alleviate the hyperalgesia state by an inhibition of local prostaglandin E2 secretion.

[Effect of Electroacupuncture at Distal and Proximal Acupoints on Expression of Spinal p 38 Mitogen-activated Protein Kinase and Cyclic Adenosine 3',5'-monophosphate in Rats with Lumbago].

OBJECTIVE: To observe the influence of Electroacupuncture (EA) stimulation of different distal-proximal acupoints combination groups on pain reaction, spinal p 38 mitogen-activated protein kinase (p 38 MAPK) expression and cyclic adenosine 3', 5'-monophosphate (cAMP) content in experimental lumbago rats. METHODS: Seventy-eight male SD rats were randomized into normal, model, sham operation, EX-B 2-BL 25 (proximal acupoints, PA), BL 40-BL 60 (distal acupoints, DA) and DA+PA groups. The lumbago model was established by implanting the autologous nucleus pulposus to the site close to the left L 5 dorsal root ganglion and the surface of dura mate of spinal cord. EA (2 Hz/100 HZ,1-3 mA) was applied at bilateral EX-B 2-BL 25 or BL 40-BL 60 or both for 20 minutes, once daily for 7 days. The mechanical pain threshold was measured, and the expression of p 38 MAPK in the lumbar spinal cord was detected by immunohistochemistry and Western blot, separately. The content of cAMP in spinal cord (L 4-L 6) was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: After mode-ling, the mechanical pain threshold percentages were significantly decreased on day 3, 5 and 7 (P<0.01), and after EA stimulation of DA,PA and DA+PA, the decreased pain threshold was significantly increased at the 3 time-points (P<0.01), and the effects of both PA and DA+PA were markedly superior to that of DA (P<0.05, P<0.01). Following modeling, lumbar spinal p 38 MAPK immunoactivity and protein expression, and cAMP content were obviously up-regulated (P<0.01). Compared with the model group, the levels of p 38 MAPK immunoactivity and protein expression in the 3 EA groups and the sham group, and cAMP contents in both PA and DA+PA groups (not in the DA and sham groups) were considerably down-regulated (P<0.01, P<0.05). CONCLUSIONS: EA stimulation of distal+proximal acupoints and proximal acupoints near the focus can raise pain threshold in lumbago rats, which may be associated with their effects in suppressing lumbago-induced increase of expression of spinal p 38 MAPK protein and cAMP content. The effects of EA of distal+proximal acupoints and proximal acupoints are better than those of EA of simple distal acupoints.

[Development of Researches on Mechanisms of Acupoint Combination for Some Disorders in Nerve-humoral-immunological Modulation].

Proper combination of acupoints is one of the core issues of acupuncturology, and is also one of the factors affecting clinical outcomes. In the present paper, the authors make a review on the development of researches on the underlying mechanisms of acupoint combination for some clinical disorders from nerve system, humoral factors and immunological regulation. The neural mechanism involves both the peripheral nervous system (mainly the segmental innervation) and central nervous system (spinal cord, brainstem, hypothalamus, cerebral cortex and cerebellum) , while the humoral factors chiefly contain neurotransmitters and hormones of the endocrine system. The immunological mechanisms involve immunocytes and cytokines. Generally speaking, following acupuncture stimulation of different combined-acupoints or acupoint groups, some synergistic effects may be produced. In fact, the relatively specific clinical effect may be easy to be obtained at the peripheral segmental innervations level.

Intraoperative and postoperative anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation combined with sufentanil anaesthesia in patients undergoing supratentorial craniotomy.

OBJECTIVES: To investigate the anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation (TEAS) during supratentorial tumour resection for postoperative recovery and side effects. METHODS: In a blinded clinical trial, 92 patients scheduled for supratentorial craniotomy under general anaesthesia were randomly allocated into either a multipoint TEAS (n=46) or a sham TEAS group (n=46). All patients received total intravenous anaesthesia (TIVA) with propofol and sufentanil. The target concentration of sufentanil was adjusted and recorded according to mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). Patients in the TEAS group received TEAS 30 min before anaesthesia induction and this was maintained throughout the operation at four pairs of acupuncture points. Postoperative pain, recovery and side effects were evaluated. RESULTS: Eighty-eight patients completed the study. Continuous monitoring of MAP, HR and BIS showed stable values with no significant differences between the two groups (p>0.05). Sufentanil target plasma concentration in TEAS patients was significantly lower at some time points during supratentorial craniotomy, and total sufentanil consumption was significantly higher in the sham group (p<0.05). Postoperative recovery and pain were significantly improved by TEAS (p<0.001), without the postoperative side effects. CONCLUSIONS: Multipoint TEAS at both proximal and distal points combined with TIVA can significantly decrease intraoperative sufentanil requirements, increase pain relief on postoperative day 1 and improve postoperative recovery of patients during supratentorial tumour resection, with no significant increase of side effects. These findings suggest that multipoint TEAS may be clinically effective as an adjunct to analgesia in intraoperative anaesthesia and postoperative pain treatment and may speed recovery. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (registration number ChiCTR-TRC-10001078).

Electro-acupuncture decreases postoperative pain and improves recovery in patients undergoing a supratentorial craniotomy.

We performed this study to examine the effect of electro-acupuncture (EA) on postoperative pain, postoperative nausea and vomiting (PONV) and recovery in patients after a supratentorial tumor resection. Eighty-eight patients requiring a supratentorial tumor resection were anesthetized with sevoflurane and randomly allocated to a no treatment group (Group C) or an EA group (Group A). After anesthesia induction, the patients in Group A received EA at LI4 and SJ5, at BL63 and LR3 and at ST36 and GB40 on the same side as the craniotomy. The stimulation was continued until the end of the operation. Patient-controlled intravenous analgesia (PCIA) was used for the postoperative analgesia. The postoperative pain scores, PONV, the degree of dizziness and appetite were recorded. In the first 6 hours after the operation, the mean total bolus, the effective times of PCIA bolus administrations and the VAS scores were much lower in the EA group (p < 0.05). In the EA group, the incidence of PONV and degree of dizziness and feeling of fullness in the head within the first 24 hours after the operation was much lower than in the control group (p < 0.05). In the EA group, more patients had a better appetite than did the patients in group C (51.2% vs. 27.5%) (p < 0.05). The use of EA in neurosurgery patients improves the quality of postoperative analgesia, promotes appetite recovery and decreases some uncomfortable sensations, such as dizziness and feeling of fullness in the head.

Regional homogeneity analysis on acupoint specificity with resting-state functional magnetic resonance imaging.

BACKGROUND: The mechanism of acupuncture analgesia in craniotomy has been widely studied. However, the theoretical basis for selection of acupoints has not been examined. In this study, we used the regional homogeneity method blood oxygen level-dependent (BOLD) signals to determine changes in brain activity in response to transcutaneous electrical stimulation on acupoints and non-acupoints in resting state functional magnetic resonance imaging (fMRI). METHODS: Twelve healthy volunteers were enrolled in this study. BOLD fMRI scanning of the brain was performed for 306 seconds before and 30 minutes after transcutaneous electrical stimulation on acupoints UB63 (Jinmen), LV3 (Tai chong), ST36 (Zusanli), and GB40 (Qiuxu). The procedure was repeated after one week with stimulation on non-acupoints (one was 9 above BL67, the second was 12 above BL67 (Kunlun), the third was 7 above KI3, and the fourth was 10 above KI3 (Taixi)). RESULTS: The regional homogeneity in the acupoint group was increased in the left thalamus, caudate, putamen, lentiform nucleus (BA19, 30, 39), postcentral gyrus, precentral gyrus (BA3, 4, 30, 32), calcarine fissure, middle temporal gyrus (BA30), right superior temporal gyrus, inferior temporal gyrus (BA38), cuneus, and precuneus (BA7, 19) when compared to the non-acupoint group. The regional homogeneity of the acupoint group was decreased in the left cerebellum posterior lobe, middle frontal gyrus (BA10), double-side precuneus (BA7), and the postcentral gyrus (BA40). CONCLUSIONS: The brain region activated following acupoint stimulation is the ipsilateral pain-related brain region, which may relate to the therapeutic effect of acupuncture on pain relief. Further acupoint stimulation causes different central nervous responses compared to non-acupoint stimulation.

[Effect of electroacupuncture on Sevoflurane anesthesia in patients undergoing resection of supratentorial tumor].

OBJECTIVE: To observe the supplementary analgesic effect of electroacupuncture and its influence on the maintenance of anesthesia and the speed of recovery of patients undergoing craniotomy. METHODS: Eighty cases of supratentorial tumor resection were randomly divided into group A and group S, 40 cases in each group. All the patients were anesthetized with 2% Sevoflurane. The patients in group A received electroacupuncture at Hegu (LI 4) and Waiguan (TE 5), Jinmen (BL 63) and Taichong (LR 3), Zusanli (ST 36) and Qiuxu (GB 40) from anesthesia beginning to the end of operation, and in group S without electroacupuncture. The end-tidal Sevoflurane concentration, minimum alveolar concentration (MAC), bispectral index (BIS) and the information during anesthesia recovery stage were recorded, respectively. RESULTS: The end-tidal concentration and MAC of Sevoflurane in group A at all times were significant lower than those in group S (P<0.05, P<0.01) with a Sevoflurane saving of 9.62% on average. The BIS in group A during a few phases were higher than that in group S (all P<0.05). During anesthesia recovery stage, the time of each phase in group A was significantly shorter than that in group S (all P<0.01). No dysphoria and one case with nausea and vomiting were shown in group A, but in group S, 2 patients had dysphoria and 3 patients had nausea and vomiting. CONCLUSION: Electroacupuncture combined with Sevoflurane anesthesia can decrease the dosage of Sevoflurane, shorten the recovery time of anesthesia and improve the quality of anesthesia recovery of the patients undergoing resection of supratentorial tumor.