THE INTERACTION BETWEEN PERIAQUEDUCTAL GRAY AND NUCLEUS ACCUMBENS IN ACCELER-ATING THE RELEASE OF ENKEPHALINS AND β-ENDORPHIN

There is a growing body of evidence showing that periaqueductal gray (PAG) and nucleus accumbens (N. accumbens) play important roles in the modulation of nociception. In our previous study of the mechanisms of morphine analgesia we found that opioid antagonist naloxone injected into either of the two nuclei, PAG or N. accumbens, could

Analgesic action of suspended moxibustion in rats with chronic visceral hyperalgesia correlates with enkephalins in the spinal cord

Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.

EFFECTS OF ACUPUNCTURE ON THE CONTENTS OF ENKEPHALINS IN DIFFERENT BRAIN REGIONS AND CORTICOSTERONE IN PLASMA OF RATS WITH ENDOTOXIN SHOCK

In this experiment,we have observed the effects of acupuncture on the contents ofenkephalins in different brain regions and corticosterone in plasma of rats with endotoxin shock.Theresults showed that after acupuncture the endogenous enkephalins were significantly decreased(P【0.05)in the midbrain and brain stem of endotoxin shock rats,suggesting the anti-shock of acupuncture might be related to the enkephalins in the midbrain and brain stem.In addition,there was a rising trend in plasma corticosterone of the rats with toxic shock.

Effectiveness and safety of electroacupuncture analgesia in controlling intraoperative pain and hemodynamics during total thyroidectomy:A randomized controlled trial

Objective:To evaluate the effectiveness and safety of electroacupuncture in conjunction with additional medications in providing analgesia and stabilizing hemodynamic parameters during total thyroidectomy.Methods:This randomized controlled trial included 100 patients who underwent a total thyroidectomy between October 2022 and October 2023 at the Vietnam National Hospital of Acupuncture.The patients were randomized into two groups.The electroacupuncture analgesia(EA)group received EA stimulation at five acupuncture points:Hegu(LI 4),Neiguan(PC 6),Shuitu(ST 10),Quepen(ST 12),and Yifeng(SJ 17),while the control group received a bilateral superficial cervical plexus block.Primary outcomes included the level of analgesia and perioperative vital signs in both groups.Additionally,pain thresholds and serum b-endorphin levels were measured before and after electroacupuncture in the EA group.Results:Complete analgesia(Level A)was attained in 86%and 76%of the patients in the EA and control groups,respectively,with no significant difference between the two groups(P=1.00).In the EA group,the mean pain threshold after receiving EA doubled(648.7(77.4)g/s vs.305.3(45.3)g/s,P<.001),and the mean serum b-endorphin level increased by approximately 13.5 pg/mL(P<.001).All patients remained hemodynamically stable throughout the surgery.Conclusion:EA,in conjunction with additional medications that stimulate five acupuncture points,LI 4,PC 6,ST 10,ST 12,and SJ 17,was well tolerated and effectively maintained a suitable level of analgesia and hemodynamic stability during total thyroidectomy.

Serotonin样,Substance P样,Enkephalin样反应阳性神经元胞体在大鼠中缝核簇内的分布

本文用PAP法研究了Serotonin样,Substance P样,Leucine—Enkephalin样和Methionine—Enkephalin样反应阳性神经元胞体在大鼠中缝核簇内的分布。证明Serotonin存在于中缝苍白核、中缝隐核、中缝大核、中缝桥核、中央上核和中缝背核等处的某些神经元胞体内。以中、小细胞为主,在中缝大核内有少数大细胞。细胞形态为梭形、圆形、卵圆形以及多极细胞。Substance P样反应阳性胞体在上述中缝核内也被发现,其胞体的大小、形态和分布与serotonin样反应阳性胞体相似,但数目稍少。Leucine—Enkephalin样反应阳性胞体存在于中缝苍白核、中缝隐核、中缝大核、中缝桥核、中缝背核和中央上核内,但Methionine—Enkephalin样反应阳性细胞体仅在中缝苍白核和中缝隐核的吻侧部以及中缝大核内发现。后两者均以大,中型多极细胞为主。

[D-Pen^2,D-Pen^5]enkephalin及Nor-binaltorphimine对吗啡损害小鼠自主选择能力的影响

选择性δ阿片受体激动剂[D-Pen^2,D-Pen^5]enkephalin(DPDPE),k阿片受体拮抗剂nor-bindtorphimine(N-BNI)在测试剂量下对小鼠在丫形迷宫中的自主选择能力无明显影响,但均可显著增强吗啡损害小鼠自主选择能力的作用。DPDPE对吗啡的协同作用还可被δ阿片受体拮抗剂ndltrindole(NTI)所拮抗。

达格列净治疗2型糖尿病合并慢性心力衰竭患者的疗效分析

目的 观察达格列净治疗慢性心力衰竭(CHF)合并2型糖尿病(T2DM)患者的疗效和结局。方法 选择我院及青岛大学附属医院80例CHF合并T2DM住院患者,分为对照组(常规治疗组)、联合达格列净组,按照随机数字法分析法分组;观察两组患者治疗前后相关指标、临床疗效随访结果的变化情况。结果 对照组及实验组治疗前后对比糖化血红蛋白(HbAC1)、N末端脑钠肽前体(NT-praBNP)、左室射血分数(LEFV)、6分钟步行距离均有统计学意义(P<0.05),对照两组患者住院治疗6月后临床总有效率比较,差异有统计学意义(P<0.01),联合治疗组总有效率高于常规治疗组。两组患者心衰再住院率和主要不良心血管事件(M A C E)发生率差异有统计学意义(P<0.01),联合治疗组心衰再住院率达格列净、沙库巴曲缬沙坦联合治疗组心衰总体生存率明显好于对照组。结论 达格列净联合沙库巴曲缬沙坦治疗临床疗效改善明显,有效控制血糖的同时可降低患者心衰再住院率及主要恶性心血管事件(MACE)发生率。

Midbrain enkephalin expression in a rat migraine model following intragastric scorpion powder administration

Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine at mRNA and protein levels. Results confirmed that migraine rat abnormal behavior was significantly improved, and proenkephalin mRNA expression was significantly increased following treatment with scorpion. The number of methionine-enkephalin- positive cells in the migraine rats following treatment with scorpion was significantly increased, but no significant difference in the number of leucine-enkephalin-positive cells was detectable compared with migraine and normal rats. Taken together, these results show that scorpion exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine rats.

Effects of Toutongning capsule on enkephalin expression in a rat migraine headache model

Toutongning capsule is used for the treatment of migraine headaches, and has yielded therapeutically beneficial effects. However, whether Toutongning capsule exerts its effects via endogenous opioid peptides remains poorly understood. This study investigated the effects of Toutongning capsule on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine headache at the mRNA and protein levels. Results confirmed that proenkephalin mRNA levels were significantly upregulated following treatment with Toutongning capsule. The numbers methionine-enkephalin and leucine-enkephalin-positive cells were significantly greater in the migraine headache rats following treatment with Toutongning capsule compared with the model group. Taken together, these results show that Toutongning capsule exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine headache rats.

Effects of electric field stimulation on endogenous enkephalin content in artery wall

After 20min electric field stimulation,L-enkephalin （L-ENK） content in the rabbitear artery declined from the control value of 38.99±17.29 to 12.55±1.96pg/mg of wet tissue（n=12）,and M-enkephalin （M-ENK） content from 134.67±8.11 to 73.68±17.96pg/mg of wet tis-sue （n=6）,both being significantly decreased.This effect was not influenced after blockade ofadrenergic receptor by yohimbine.Contractions of artery strips induced by electric field stimulationwere enhanced distinctly after pretreatment of the artery strips with naloxone,an opioid receptorblocker,and with pronase,but not after pretreatment with trypsin.The results suggested that the re-lease of endogenous enkephalins in the ear artery could be induced by electric field stimulation andx2-receptor might not participate in the release course,The release amount of ENK from the ar-terv strips increased when the stimulus freduency increased within the range of 2 Hz to 8 Hz.

Conceptual Density Functional Theory Study of the Chemical Reactivity Properties and Bioactivity Scores of the Leu-Enkephalin Opioid Peptide Neurotransmitter

The SMD solvation model (Solvation Model based on the Density) and eight density functionals, CAM-B3LYP, LC-ωPBE, M11, MN12SX, N12SX, ωB97, ωB97X, and ωB97XD, were assessed in link with the Def2TZVP basis set for the calculation of the structure of the Leu-Enkephalin Opioid Peptide Neurotransmitter as well as their molecular properties. Through the Conceptual Density Functional Theory (CDFT), the entire chemical descriptors for the system were calculated. The active regions of the molecules necessary for electrophilic, nucleophilic and radical attacks were chosen through linking them with the corresponding Fukui functions. Furthermore, the prediction of the pKa value for the peptide is done with great accuracy as well as the ability of the studied molecule in acting as an efficient inhibitor of the formation of Advanced Glycation Endproducts (AGEs), which comprises of a useful knowledge for the development of drugs for preventing Alzheimer, Diabetes and Parkinson diseases. Lastly, the bioactivity scores for the studied peptides are predicted via various methodologies.

Plasma leucine enkephalin content in patients with “Liver-blood deficiency” syndrome and clinical significance

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Effects of methionine enkephalin on immune enhancement by reducing myeloid derived suppressor cells and reprogramming liver metabolism in colon cancer mice

OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg^(-1) for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TG test kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure m RNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTS MENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4^+T and CD8^+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TG and T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL^(-1)β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.

EFFECT OF METHIONINE ENKEPHALIN ON MIGRATION OF MACROPHAGES FROM MICE WITH IMPAIRED LIVER

Objective To observe the effects of methionine enkephalin (M Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. Methods Liver of mice was impaired by feeding CCl 4 and macrophage migration inhibitory factor (MMIF) was produced by Con A stimulated spleen lymphocytes. Inhibition of macrophage migration was measured in reaction system by adding M Enk. Results Migration of macrophages in both liver impaired and control group were suppressed by MMIF, but the suppression might be reversed by adding 1 μmol/L M Enk ( P <0.05).M Enk could significantly inhibit in vitro both of the combination of MMIF with macrophages and production of MMIF from lymphocytes ( P <0.01).Macrophages from liver imparied group showed a higher sensitivity compared to the control group ( P <0.05).Conclusion The study suggests that opioid peptieds play an important role in the modulation of the immune response under stress as liver impairment.

Changes of Immunoreactive β-Endorphin in Plasma, Pituitary and Hypothalamus of Rats during Oxygen-Induced Convulsions

We observed for the first time the differences of immunoreactive β-endorphin(IR -β- EP) content in plasma, pituitary and hypothalamus of rats under various conditionsusing radioimmunoassay (RIA) and the effects of naloxone and β - endorphin (β- EP) antiserumon initial time of convulsions (ITC), severity of convulsions(SOC) and mortality on surface(MOS) of rats to hyperbaric oxygen(HBO). The results suggest thatβ- EP may partici-pate in the course of oxygen - induced convulsions and be one of endogenous convulsion - causingagents.

Effects of plasma β-endorphin on hemorrhagic shock in acute hypoxic rats

Forty rots were randomized into 2 groups and naloxone or saline were injected to therats after they were inflicted with hemorrhagic shock at sea level and at a simulated altitude of4000m respectively to observe the effects of naloxone on left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVDP),the maximal changing rate of LVSP(dp/dt max),heartrate(HR),and survival time of the animals.Plasma β-endorphin(β-EP)was determined beforeand after hemorrhage to observe the relationship between β-EP and hemorrhagic shock.It wasfound that the circulatory parameters of hemorrhagic shock changed more markedly at high alti-tude than at sea level,naloxone could restore these parameters and prolong the survival time inboth the animals of the sea level and high altitude groups,and plasma β-EP level was elevatedafter hemorrhage especially in those animals at high altitude.These findings indicate:(1)Hemorrhagic shock at high altitude is usually accompanied with severe clinical manifestations,rapid progression,and high mortality.(2)β-EP seems to participate in the pathologicalmanifestafions of hemorrhagic shock at high altitude,and its depressive action on myocardialcontraction may be one of the factors inducing hemorrhagic shock.(3)Naloxone possesses defi-nite property to comet hemorrhagic shock at high altitude.

Changes in beta-endorphin neuron numbers and serum hormone levels in the arcuate nucleus of ovariectomized rats undergoing treadmill exercise

BACKGROUND： The arcuate nucleus, when damaged in young rats, can lead to pathological changes in adults, such as osteoporosis. Ovariectomized rats suffer from osteoporosis at eight weeks following surgery and the number of β -endorphin immunoreactive neurons in the arcuate nucleus of the hypothalamus is significantly decreased. OBJECTIVE： To establish a rat model of osteoporosis using ovariectomy and to explore changes in the number of β-endorphin neurons and to correlate any such change with serum hormone levels in response to exercise or rest. DESIGN, TIME AND SETTING： The completely randomized block design, neural morphology study was performed at the Key Laboratory of Physiology, Guangdong Medical College, China between March 2004 and January 2005. MATERIALS： Sixteen healthy female rats were selected for ovariectomy. METHODS： Following model establishment, rats were assigned to either rest or exercise groups and each rat was housed individually. Rats in the exercise group underwent an exercise regimen using a treadmill. MAIN OUTCOME MEASURES： Eight weeks following exercise, radioimmunoassay was performed to detect serum growth hormone, estrogen and osteocalcin levels. Immunohistochemistry was used to measure changes in the number of β -endorphin neurons in the arcuate nucleus of the hypothalamus. Changes in bone metabolism were assessed using bone histomorphometry. RESULTS： In the exercise group, the β -endorphin immunoreactive neurons were high in number, darkly stained, and the nucleus was not obvious. In the rest group, the β -endorphin immunoreactive neurons were low in number and lightly stained. The number of β-endorphin immunoreactive neurons in the exercise group was higher compared with the rest group （t = 2.83, P 〈 0.05）. Estrogen levels were similar between the rest and exercise groups （P 〉 0.05）. Serum osteocalcin and growth hormone levels were significantly higher in the exercise group compared with the rest group （t = 2.78, 2.32, P 〈 0.05）. Compared with the rest group, the percentage of trabecular bone area, trabecular thickness, and trabecular number were significantly increased, but trabecular separation was significantly reduced （t=2.48, 2.57, 2.32, 3.06, P 〈 0.05） in the exercise group. In the exercise group, the trabeculae of the tibia were arranged regularly and were high in number. In the rest group, the trabeculae of the tibia were organized in a disorderly manner and were low in number, with many fat particles. CONCLUSION： Exercise promotes bone growth and delays osteoporosis by inducing an increase in the number of β-endorphin immunoreactive neurons in the arcuate nucleus of the hypothalamus and by increasing serum growth hormone and osteocalcin levels.

EFFECTS OF β-ENDORPHIN ON PHYTOHEMAGGLUTININ-INDUCED LYMPHOCYTE PROLIFERATION AND MOUSE PLAQUE-FORMING CELL RESPONSE VIA AN OPIOID RECEPTOR MECHANISM

The effects of opioid peptides on iminune responses were investigated. It was found that β-endorphin (β-END) can depress proliferative responses to PHA in rat splenocytes but enhance those in mice, and it could also inhibit the plaque-forming cell (PFC) response to sheep red blood cells when mouse splenocytes immunized in vivo were cultured in vitro with the peptide. The peptide antagonist naloxone was able to reverse β-END suppression of the PFC response. The data indicate that β-END suppresses antibody production or secretion via a specific opioidreceptor-mediated mechanism.

Effects of Peripherally Acting Opioid Ligands on Central Opioid Receptors and <i>β</i>-Endorphin Release in Stressed Rats

Using the radioreceptor binding assay, μ-opioid receptor (MOR) affinity in the midbrain of stressed rats was higher than in naive controls. MOR density in the rat frontal cortex was reduced after stress. Intragastric administration of the MOR antagonist naloxone methiodide was followed by an increase in the number of MORs in the frontal cortex. However, the MOR agonist loperamide significantly decreased the density of MORs in the frontal cortex and midbrain of naive animals. Loperamide and naloxone methiodide were shown to prevent an increase in MOR affinity and a decrease in MOR density in the midbrain of rats after restraint stress. The restraint stress was accompanied by an increase in the release of β-endorphin (BE) in the ventral tegmental area (VTA) of control rats. After administration, loperamide slightly decreased the release of BE, naloxone methiodide significantly increased the release of BE in the cingulate cortex (CC) of untreated animals, while drugs had no effect on the release of BE in the VTA. The drugs significantly increased the extracellular level of BE in the CC of stressed animals. Loperamide abolished the increase in the stress-induced release of BE in the VTA. By contrast, naloxone methiodide significantly increased the release of BE in the VTA of stressed rats. Our data indicated that activation of peripheral MORs induces depression of the central part of the μ-opioid system, but suppression of peripheral MOR activity induces activation of the central μ-opioid system, the interaction of which can be modulated by stress.

RELATIONSHIP BETWEEN ACUPUNCTURE ANALGESIA AND MET-ENKEPHALIN OR DYNORPHIN

subjective: The effect of 4～5 Hz electroacupuncture (EA) on alterations of both met enkephalin (MEK) and dynorphin (Dyn) in the patient plasma or mouse spinal cord and its relation with analgesic effect were studied.Methods: In acupuncture clinic 10 patients with acute pain were treated with 4 Hz EA at Zusanli(ST 36) and/or Hegu(LI 4) acupoints for 30 min. 20 BALB/C mice were randomly divided into 2 groups: a. EA group(n=10), treated with 4～5 Hz EA at bilateral “Zusanli"(ST 36) for 15 min; b. control group(n=10) treated with no EA, but also restrained for 15 min. Before and after EA or restraining acupoints, the pain threshold of the patients or mice was detected. 10 μl of the patient plasma before and after EA and each mouse spinal cord suspension, of the 2 groups were blotted onto nitrocellulose membrane (NCM) respectively. The protein dot blot signals were detected by immunoreactivity (IR) and using Shimadu TLC Scanner and analyzed statistically. Results: The results showed that an increase in patient plasma MEK IR or Dyn IR and a decrease in mouse spinal MEK IR or Dyn IR could be detected, and the alteration of plasma or spinal MEK IR was more significant than that of plasma or spinal Dyn IR. There was a positive correlation in alteration between plasma or spinal MEK IR and plasma or spinal Dyn IR with respective parallel levels in individuals. The increased plasma MEK IR or the decreased spinal MEK IR was positively or negatively correlated with the analgesic effect, while the correlation between plasma or spinal Dyn IR and analgesic effect was insignificant. Conclusion: The results suggest that under lower frequency EA the met enkephalin may play an important role in analgesia.