The endogenous opioid system plays a significant role in the modulation of distress in many psychiatric, neurologic, and neurodevelopmental disorders. Many clinical distress symptoms show similarities to the excitator...The endogenous opioid system plays a significant role in the modulation of distress in many psychiatric, neurologic, and neurodevelopmental disorders. Many clinical distress symptoms show similarities to the excitatory autonomic withdrawal effects in chronic opioid-dependent animals and humans, as well as to the “quasi-morphine withdrawal syndrome” evoked in naive rodents shortly after acute systemic injection of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors. These symptoms result from excessive excitatory opioid receptor signaling and increased endorphin release. Pharmacologic analyses of the remarkably plastic bimodal (excitatory/inhibitory) signaling functions of opioid receptors have utilized microelectrode recordings from opioid-sensitive neurons in tissue cultures of mouse sensory ganglia and hot-water tail-flick assays in mice. These studies led to development of specific chemical formulations that switch opioid receptor signaling from an excessively excitatory to a normal inhibitory mode. Critical combinations of cAMP-PDE inhibitors that release endorphins plus specific agents that switch opioid receptors from excitatory Gs-coupled to inhibitory Gi/Go-coupled signaling were shown to attenuate hyperalgesia and distress evoked by diverse chemical stressors in mouse tail-flick assays. Both the “quasi-morphine withdrawal syndrome” in naive rodents as well as the excitatory withdrawal effects in chronic, opioid-dependent animals and humans may be manifestations of a common Endorphinergic Distress Syndrome (EDS). We suggest that many distress symptoms are caused by EDS, a dysfunctional imbalance in the endogenous opioid system, consisting of abnormal endorphin levels, together with opioid receptors predominately in their excitatory mode. Therefore, concomitantly enhancing endogenous opioid release and switching excessive excitatory opioid receptor signaling to inhibitory signaling can attenuate these distress symptoms. Trials of a critically formulated oral preparation, containing both endorphin enhancers and opioid receptor switchers, have resulted in long-term anxiolytic efficacy and enhanced calm and mental clarity in large numbers of individuals with distress symptoms. These endorphinergic formulations may provide treatment for the emotional and physical distress associated with many psychiatric, neurologic, and neurodevelopmental disorders.展开更多
While the endogenous opioid system has generally been associated with regulation of pain, it also modulates the experience of distress and may play a central role in many psychiatric and neurodevelopmental disorders. ...While the endogenous opioid system has generally been associated with regulation of pain, it also modulates the experience of distress and may play a central role in many psychiatric and neurodevelopmental disorders. Decades of preclinical research on the analgesic effects of endogenous opioids, i.e., endorphins, suggests that opioid receptors have plastic bimodal (inhibitory/excitatory) properties that may explain conflicting findings in clinical research. An exploratory study with 60 healthy volunteer participants, using a cold pressor-induced pain paradigm, found evidence that a combination of a nutraceutical agent that enhances endorphin release (Endorphin Enhancer) with one that switches opioid receptors from an excitatory to inhibitory mode (Opioid Receptor Switcher) not only increases pain tolerance but also reduces emotional and physical distress. This discovery led to clinical application of a critically formulated endorphinergic treatment in 203 case studies over a two-year period. Findings revealed the remarkable clinical efficacy and safety of this treatment in the relief of chronic emotional and physical distress, including anxiety, anger, depression, cravings, and hyperalgesia, as well as enhancement of well-being, productivity, mental clarity, relationships, and an adaptive response to life’s stresses. These studies provide new insights into the role of endogenous opioid system imbalances in the development, treatment, and prevention of dysfunctional emotional and physical distress. We postulate that an Endorphinergic Distress Syndrome (EDS) consists of abnormal endorphin levels together with opioid receptors predominately in their excitatory mode. EDS may account for many core distress symptoms associated with chronic anxiety, addictions, pain, as well as affective personality, autism spectrum, attention-deficit, and distress-related medical problems. Our research has led to new endorphinergic formulations, combining Endorphin Enhancers, such as caffeine, with Opioid Receptor Switchers, such as n-acetylcysteine, for the relief of emotional and physical distress. Our studies also provide a novel method to reverse the anxiogenic effects of caffeine and related hyperexcitatory substances.展开更多
AIM To study the role of cholecystokinin- octapeptide (CCK-8). β-endorphin (β-EP). and gastrin in an anorexic infantile rat model and no subsequent regulation of nose peptides by the Yunpi complex prescription Er...AIM To study the role of cholecystokinin- octapeptide (CCK-8). β-endorphin (β-EP). and gastrin in an anorexic infantile rat model and no subsequent regulation of nose peptides by the Yunpi complex prescription ErBao Granule. METHODS We fed infantile rats with special prepared forage. A liquid extract of ErBao Granule was administered to the rats daily for 3 weeks, CCK-8, β-EP, and gastrin concentrations in hypothalamus, gastric antrum, and plasma of the rats were measured by radioimmunoassay, and were compared with controls. RESULTS Treatment of rats with ErBao Granule inhibited CCK-8 secretion and increased β-EP and gastrin secretion. CCK-8 concentration in hypothalamus and plasma of model control group increased significantly and correlated negatively with food intake of models, respectively. β-EP concentration in gastric antrum and plasma of model control group decreased significantly and showed a positive correlation with food intake of models, respectively. Hypothalamus concentration of β -EP was similar in models and controls. Gastrin concentration in gastric antrum of models was lower than in the blank control group, and correlated positively to food intake of models. Finally, CCK-8 concentrations in plasma of rats showed a positive correlation with plasma β-EP (r=-0.68, P<0.05). CONCLUSION The increased plasma and hypothalamus concentration of CCK-8, decreased gastric antrum and plasma level of β -EP, and decreased gastric antrum concentration of gastric are associated significantly with the anorexia of infantile anorexic rat models produced by special forage. ErBao Granule can reverse these changes, which may be the major mechanisms of ErBao Granule simulating feeding.展开更多
Aim： To access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups. Methods： Beta-endorphin was estimated in the serum and seminal plasma by enzyme-linked immunosorbent assay ...Aim： To access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups. Methods： Beta-endorphin was estimated in the serum and seminal plasma by enzyme-linked immunosorbent assay （ELISA） method in 80 infertile men equally divided into four groups： non-obstructive azoospermia （NOA）, obstructive azoospermia （OA）, congenital bilateral absent vas deferens （CBVAD） and asthenozoospermia. The results were compared to those of 20 normozoospermic proven fertile men. Results： There was a decrease in the mean levels of betaendorphin in the seminal plasma of all successive infertile groups （mean ± SD： NOA 51.30 ± 27.37, OA 51.88 ± 9.47, CBAVD 20.36 ± 13.39, asthenozoospermia 49.26 ± 12.49 pg/mL, respectively） compared to the normozoospermic fertile control （87.23 ± 29.55 pg/mL）. This relation was not present in mean serum level of beta-endorphin between four infertile groups （51.09 ± 14.71, 49.76 ± 12.4, 33.96 ± 7.2, 69.1 ± 16.57 pg/mL, respectively） and the fertile control group （49.26 ± 31.32 pg/mL）. The CBVAD group showed the lowest seminal plasma mean level of beta-endorphin. Testicular contribution of seminal beta-endorphin was estimated to be approximately 40%. Seminal beta-endorphin showed significant correlation with the sperm concentration （r = 0.699, P = 0.0188） and nonsignificant correlation with its serum level （r = 0.375, P = 0.185） or with the sperm motility percentage （r = 0.470, P = 0.899）. Conclusion： The estimation of beta-endorphin alone is not conclusive to evaluate male reproduction as there are many other opiates acting at the hypothalamic pituitary gonadal axis.展开更多
β-endorphin is the most actively endogenous substance of cerebral endorphin. When combined with opiate receptor specially, it manifests a strong morphine-like activity and can decrease sensitivity of central nervous ...β-endorphin is the most actively endogenous substance of cerebral endorphin. When combined with opiate receptor specially, it manifests a strong morphine-like activity and can decrease sensitivity of central nervous system to carbon dioxide so as to inhibit breath. OBJECTIVE： To observe the changes of content of plasma β-endorphin in neonates with severe asphyxia after naloxone treatment in a large dosage. DESIGN： Randomized controlled observation. SETTINGS： Department of Pediatrics, Shenzhen Shajing People＇s Hospital; Center of Pediatrics, Guangzhou Zhujiang Hospital. PARTICIPANTS： A total of 97 neonates with severe asphyxia including 57 boys and 40 girls were selected from Neonatal Intensive Care Unit, Department of Pediatrics, Shenzhen Shajing People＇s Hospital from January 2004 to November 2005. Their gestational age was （38±3） weeks, body mass was （3.2±1.7） kg, and hospitalization duration was （2.8±2.3） hours. All neonates met the diagnostic criteria of with severe asphyxia and all their parents provided the confirmed consent. METHODS： All neonates were treated with inspired oxygen, sedation, stopping terror, decreasing cranial pressure, maintaining a well blood perfusion and normal level of blood glucose （about 5.0 retool/L）. After hospitalization, 0.1 mg/（kg·d） naloxone hydrochloride （Beijing Sihuan Pharmaceutical Technology Co., Ltd.; certification： HI0900021; bullet preparation; 0.4 mg/ampoule） was intravenously dribbled into neonates for 4 - 6 hours, 14 days in total. 2 mL blood was collected from radial artery in neonates at the beginning of hospitalization and at 3 days after naloxone treatment, put in aprotinin-pre-cool tube, mixed evenly, and centrifuged at hypothermia. Plasma was maintained in refrigerator at - 70 ℃. The kit was provided by Neurobiology Department of Shanghai Second Military Medical University of Chinese PLA. Concentration of plasma β-endorphin was measured by using radio-immunity assay.All data were expressed as Mean ± SD and results were compared with paired t test. MAIN OUTCOME MEASURE： Concentration of plasma β-endorphin. RESULTS： All 97 neonates were involved in the final analysis. Concentration of plasma β-endorphin in neonates with severe asphyxia was lower after treatment as compared with that before treatment, and there was significant difference （t = 10.31, P 〈 0.01 ）. CONCLUSION： Naloxone can decrease level of plasma β-endorphin in neonates with severe asphyxia.展开更多
We evaluated the effects of β-endorphin (β-EP) antiserum administrated intravenously and intracisternally on the ischemic arrhythmia induced by coronary ligation in SD rats. It was found that β-EP antiserum given i...We evaluated the effects of β-endorphin (β-EP) antiserum administrated intravenously and intracisternally on the ischemic arrhythmia induced by coronary ligation in SD rats. It was found that β-EP antiserum given intracisternally but not intravenousllyreduced the severity of ischemic arrhythmia. These results indicate that central β -EP may be involved in the mechanisms of ischemic arrhythmia.展开更多
Endorphins are the body's natural opioids that are created and released by the central nervous system, hypothalamus and pituitary gland. Endorphins have a reputation for pain reduction, enhancing excitement or sat...Endorphins are the body's natural opioids that are created and released by the central nervous system, hypothalamus and pituitary gland. Endorphins have a reputation for pain reduction, enhancing excitement or satisfaction, boosting confidence, enabling control of emotions and generating feelings of euphoria, and are involved in the natural reward cycle. There is also evidence in the literature suggesting the role of endorphins in sexuality(including sexual function and sexual behaviours), as they may regulate the release of sex hormones, prolactin and growth hormone, which are involved in sexual function and love. Endogenous oxytocin is another intrinsic hormone whose role in inducing labour contractions, the delivery of the baby and stimulating lactation has been well studied. However, the potential impact of endorphins and oxytocin on sexuality and romantic relationships is not well understood. This article reviews the research on endorphins and endogenous oxytocin and how they relate to human sexuality and romantic relationships. Some animal studies report the effect of endorphin and oxytocin on sex hormones and mating behaviours, but these findings have not been supported by research into human behaviour, indicating many gaps in knowledge relating to the association between these hormones and human sexuality.展开更多
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 num...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.展开更多
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 ef...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.展开更多
BACKGROUND： Several studies have confirmed that endothelin and endorphin are involved in the occurrence of cerebral vasospasm. However, the correlation of these factors to acute cerebral infarction-related risk facto...BACKGROUND： Several studies have confirmed that endothelin and endorphin are involved in the occurrence of cerebral vasospasm. However, the correlation of these factors to acute cerebral infarction-related risk factors needs to be confirmed. OBJECTIVE： To detect endothelin-1 （ET-1） and beta-endorphin （β -EP） levels in plasma of patients with acute cerebral infarction, and to analyze the correlations of these factors to smoking, alcohol abuse, hypertension, diabetes mellitus, diseased region, diseased degree, gender, and other factors related to acute cerebral infarction. DESIGN： A case-control observation. SETTING： First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine; Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University. PARTICIPANTS： Sixty-nine inpatients with acute cerebral infarction were admitted to the Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University （March 2003-January 2004） and First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine （March July 2004） and recruited for this study. All 69 inpatients corresponded to the diagnosis criteria of acute cerebral infarction, formulated in the National Working Conference of Cerebrovascular Disease in 1998, and were confirmed as acute cerebral infarction by CT/MRI. The patient group consisted of 35 males [（644- 12） years old] and 34 females[ （674- 13 ） years old]. Among them, 9 patients were smokers, 7 were alcohol users, 48 had a history of hypertension, and 16 had a history of diabetes mellitus. CT/MRI examinations revealed that 35 patients presented with left focus sites, 11 with right ones and 23 with bilateral ones. Following attack, 24 patients had Barthel Index Scale grading 〈 40 points, 21 patients 40-50 points, and 24 patients 〉 60 points. An additional 59 healthy individuals, who received health examinations simultaneously, were included as controls. Among the control subjects, there were 37 males [（62±10） years old] and 22 females [（65±11） years old]. Among them, 7 patients were smokers, and 6 were alcohol users. All controls had no history of stroke, hypertension, or diabetes mellitus. Informed consents of laboratory measurements were obtained from all subjects, and this study was approved by the Hospital Ethics Committee. METHODS： ① Following admission, all subjects were scored by Barthel Index Scale （BIS） and Hamilton Depression Scale. Meanwhile, hypertension, diabetes mellitus, gender, smoking, drinking, and other conditions were recorded. CT/MRI examination was conducted to identify the focus site.②On the 2^nd day after admission, ET-1 and β -EP plasma levels were measured with an automatic ET-1 and β -EP analysis kit. MAIN OUTCOME MEASURES： ET-1 and β -EP plasma levels and their correlation to acute cerebral infarction-related factors. RESULTS： Sixty-nine patients with acute cerebral infarction, and an additional 59 healthy individuals participated in the final analysis. β ET-1 [（63.80±27.65） ng/L vs. （46.50±9.36） ng/L, P 〈 0.05] and β - EP [（94.18±33.94） mg/L vs. （51.87±23.43） mg/L, P 〈 0.05] levels of the patient group were obviously higher than respective values of the control group. ② The ET-1 and β -EP levels of patients with cerebral infarction did not correlate to hypertension, diabetes mellitus, BIS, depression, cerebral infarct focus, disease course, gender, smoking or drinking （P 〉 0.05）. CONCLUSION： The ET-I and β-EP levels of patients with acute cerebral infarction increased, but they were not obviously associated with disease course, blood pressure, blood glucose, BIS, or other common cerebral infarction-related factors.展开更多
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 n...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.展开更多
To observe plasm a β-endorphin (β-EP) and gonadotrophin releasing horm one (GnRH), hum an chorionic gonadotrophin (hCG), progesterone (P4) levelsin w om en w ith early threatened abortion and w ith a history of re...To observe plasm a β-endorphin (β-EP) and gonadotrophin releasing horm one (GnRH), hum an chorionic gonadotrophin (hCG), progesterone (P4) levelsin w om en w ith early threatened abortion and w ith a history of recurrent spontaneous abortions (RSA). Tw enty patientsw ith threatened abortion at7～8 w eeksof gestation w ere re- cruited, allof them had a history of 3 or m ore recurrentunexplained abortions. They w ere treated w ith psychologicalconsultation accompanied by traditionalChinese herbs. Blood samples w ere taken to m easure β-EP, GnRH, hCG and P4 levels by radioim - m unoassay (RIA). The treatm ents w ere continued till10～12 w eeks, blood w astaken during this period to compare changes in these peptides / horm ones. Tw enty norm al pregnantw om en at7～8 and 10～12 w eeksand 20 patientsw ith incompleteabortion at 10～12 w eeksw ererecruited for comparativestudies. Results: (1) In norm alpregnant w om en, plasm a β-EP, GnRH, hCGand P4 levelsat10～12 w eeksw ere significantly higher than thatat7～8 w eeks (P< 0.01). (2) In patients w ith threatened abortion and a history of RSA, plasm a β-EP levels at7～8 w eeks w ere significantly higher than those of norm al pregnantw om en (P< 0.01); on the contrary, plasm a GnRH, hCGand P4 levelsin these patientsw ere significantly low er than thosein norm alcases (P< 0.01). After treatm ent, 16 of the 20 patients succeeded in m aintaining their pregnancies, the levels of the four plasm a contents at10～12 w eeks w ere sim ilar to thosein norm alpregnantw om en (P> 0.05). (3) Plasm a β-EPlevelsin patientsw ith incomplete abortionsat10～12 w eeksw ere dram atically higher and GnRH, hCGand P4 levelsw ere low er than in norm alpregnantw om en (P< 0.01). β-EP m ightplay a role in the pathophysiology of spontaneousabortion.展开更多
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...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.展开更多
The effect of electromagnetic field on plasma β endorphin in 30 patients with migraine were studied in the experiment. All subjects received a 20 minute repetitive transcranial magnetic stimulation (Frequency 10Hz, A...The effect of electromagnetic field on plasma β endorphin in 30 patients with migraine were studied in the experiment. All subjects received a 20 minute repetitive transcranial magnetic stimulation (Frequency 10Hz, Average intensity 8mT) per time, and the total experiment lasted 20 times. Before and after the experiment, the EEG and plasma β endorphin were tested. The results show that the level of plasma β endorphin in patients blood increased significantly from (73.486±26.002)mg/ml to (116.934±67.592)mg/ml (p<0.01), and the EEG average magnitude of the migraine patients were improved obviously from 41.77μV to 47.42μV.展开更多
文摘The endogenous opioid system plays a significant role in the modulation of distress in many psychiatric, neurologic, and neurodevelopmental disorders. Many clinical distress symptoms show similarities to the excitatory autonomic withdrawal effects in chronic opioid-dependent animals and humans, as well as to the “quasi-morphine withdrawal syndrome” evoked in naive rodents shortly after acute systemic injection of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors. These symptoms result from excessive excitatory opioid receptor signaling and increased endorphin release. Pharmacologic analyses of the remarkably plastic bimodal (excitatory/inhibitory) signaling functions of opioid receptors have utilized microelectrode recordings from opioid-sensitive neurons in tissue cultures of mouse sensory ganglia and hot-water tail-flick assays in mice. These studies led to development of specific chemical formulations that switch opioid receptor signaling from an excessively excitatory to a normal inhibitory mode. Critical combinations of cAMP-PDE inhibitors that release endorphins plus specific agents that switch opioid receptors from excitatory Gs-coupled to inhibitory Gi/Go-coupled signaling were shown to attenuate hyperalgesia and distress evoked by diverse chemical stressors in mouse tail-flick assays. Both the “quasi-morphine withdrawal syndrome” in naive rodents as well as the excitatory withdrawal effects in chronic, opioid-dependent animals and humans may be manifestations of a common Endorphinergic Distress Syndrome (EDS). We suggest that many distress symptoms are caused by EDS, a dysfunctional imbalance in the endogenous opioid system, consisting of abnormal endorphin levels, together with opioid receptors predominately in their excitatory mode. Therefore, concomitantly enhancing endogenous opioid release and switching excessive excitatory opioid receptor signaling to inhibitory signaling can attenuate these distress symptoms. Trials of a critically formulated oral preparation, containing both endorphin enhancers and opioid receptor switchers, have resulted in long-term anxiolytic efficacy and enhanced calm and mental clarity in large numbers of individuals with distress symptoms. These endorphinergic formulations may provide treatment for the emotional and physical distress associated with many psychiatric, neurologic, and neurodevelopmental disorders.
文摘While the endogenous opioid system has generally been associated with regulation of pain, it also modulates the experience of distress and may play a central role in many psychiatric and neurodevelopmental disorders. Decades of preclinical research on the analgesic effects of endogenous opioids, i.e., endorphins, suggests that opioid receptors have plastic bimodal (inhibitory/excitatory) properties that may explain conflicting findings in clinical research. An exploratory study with 60 healthy volunteer participants, using a cold pressor-induced pain paradigm, found evidence that a combination of a nutraceutical agent that enhances endorphin release (Endorphin Enhancer) with one that switches opioid receptors from an excitatory to inhibitory mode (Opioid Receptor Switcher) not only increases pain tolerance but also reduces emotional and physical distress. This discovery led to clinical application of a critically formulated endorphinergic treatment in 203 case studies over a two-year period. Findings revealed the remarkable clinical efficacy and safety of this treatment in the relief of chronic emotional and physical distress, including anxiety, anger, depression, cravings, and hyperalgesia, as well as enhancement of well-being, productivity, mental clarity, relationships, and an adaptive response to life’s stresses. These studies provide new insights into the role of endogenous opioid system imbalances in the development, treatment, and prevention of dysfunctional emotional and physical distress. We postulate that an Endorphinergic Distress Syndrome (EDS) consists of abnormal endorphin levels together with opioid receptors predominately in their excitatory mode. EDS may account for many core distress symptoms associated with chronic anxiety, addictions, pain, as well as affective personality, autism spectrum, attention-deficit, and distress-related medical problems. Our research has led to new endorphinergic formulations, combining Endorphin Enhancers, such as caffeine, with Opioid Receptor Switchers, such as n-acetylcysteine, for the relief of emotional and physical distress. Our studies also provide a novel method to reverse the anxiogenic effects of caffeine and related hyperexcitatory substances.
基金Project supported by the National Natural Science Foundation of China,No.39670896
文摘AIM To study the role of cholecystokinin- octapeptide (CCK-8). β-endorphin (β-EP). and gastrin in an anorexic infantile rat model and no subsequent regulation of nose peptides by the Yunpi complex prescription ErBao Granule. METHODS We fed infantile rats with special prepared forage. A liquid extract of ErBao Granule was administered to the rats daily for 3 weeks, CCK-8, β-EP, and gastrin concentrations in hypothalamus, gastric antrum, and plasma of the rats were measured by radioimmunoassay, and were compared with controls. RESULTS Treatment of rats with ErBao Granule inhibited CCK-8 secretion and increased β-EP and gastrin secretion. CCK-8 concentration in hypothalamus and plasma of model control group increased significantly and correlated negatively with food intake of models, respectively. β-EP concentration in gastric antrum and plasma of model control group decreased significantly and showed a positive correlation with food intake of models, respectively. Hypothalamus concentration of β -EP was similar in models and controls. Gastrin concentration in gastric antrum of models was lower than in the blank control group, and correlated positively to food intake of models. Finally, CCK-8 concentrations in plasma of rats showed a positive correlation with plasma β-EP (r=-0.68, P<0.05). CONCLUSION The increased plasma and hypothalamus concentration of CCK-8, decreased gastric antrum and plasma level of β -EP, and decreased gastric antrum concentration of gastric are associated significantly with the anorexia of infantile anorexic rat models produced by special forage. ErBao Granule can reverse these changes, which may be the major mechanisms of ErBao Granule simulating feeding.
文摘Aim： To access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups. Methods： Beta-endorphin was estimated in the serum and seminal plasma by enzyme-linked immunosorbent assay （ELISA） method in 80 infertile men equally divided into four groups： non-obstructive azoospermia （NOA）, obstructive azoospermia （OA）, congenital bilateral absent vas deferens （CBVAD） and asthenozoospermia. The results were compared to those of 20 normozoospermic proven fertile men. Results： There was a decrease in the mean levels of betaendorphin in the seminal plasma of all successive infertile groups （mean ± SD： NOA 51.30 ± 27.37, OA 51.88 ± 9.47, CBAVD 20.36 ± 13.39, asthenozoospermia 49.26 ± 12.49 pg/mL, respectively） compared to the normozoospermic fertile control （87.23 ± 29.55 pg/mL）. This relation was not present in mean serum level of beta-endorphin between four infertile groups （51.09 ± 14.71, 49.76 ± 12.4, 33.96 ± 7.2, 69.1 ± 16.57 pg/mL, respectively） and the fertile control group （49.26 ± 31.32 pg/mL）. The CBVAD group showed the lowest seminal plasma mean level of beta-endorphin. Testicular contribution of seminal beta-endorphin was estimated to be approximately 40%. Seminal beta-endorphin showed significant correlation with the sperm concentration （r = 0.699, P = 0.0188） and nonsignificant correlation with its serum level （r = 0.375, P = 0.185） or with the sperm motility percentage （r = 0.470, P = 0.899）. Conclusion： The estimation of beta-endorphin alone is not conclusive to evaluate male reproduction as there are many other opiates acting at the hypothalamic pituitary gonadal axis.
文摘β-endorphin is the most actively endogenous substance of cerebral endorphin. When combined with opiate receptor specially, it manifests a strong morphine-like activity and can decrease sensitivity of central nervous system to carbon dioxide so as to inhibit breath. OBJECTIVE： To observe the changes of content of plasma β-endorphin in neonates with severe asphyxia after naloxone treatment in a large dosage. DESIGN： Randomized controlled observation. SETTINGS： Department of Pediatrics, Shenzhen Shajing People＇s Hospital; Center of Pediatrics, Guangzhou Zhujiang Hospital. PARTICIPANTS： A total of 97 neonates with severe asphyxia including 57 boys and 40 girls were selected from Neonatal Intensive Care Unit, Department of Pediatrics, Shenzhen Shajing People＇s Hospital from January 2004 to November 2005. Their gestational age was （38±3） weeks, body mass was （3.2±1.7） kg, and hospitalization duration was （2.8±2.3） hours. All neonates met the diagnostic criteria of with severe asphyxia and all their parents provided the confirmed consent. METHODS： All neonates were treated with inspired oxygen, sedation, stopping terror, decreasing cranial pressure, maintaining a well blood perfusion and normal level of blood glucose （about 5.0 retool/L）. After hospitalization, 0.1 mg/（kg·d） naloxone hydrochloride （Beijing Sihuan Pharmaceutical Technology Co., Ltd.; certification： HI0900021; bullet preparation; 0.4 mg/ampoule） was intravenously dribbled into neonates for 4 - 6 hours, 14 days in total. 2 mL blood was collected from radial artery in neonates at the beginning of hospitalization and at 3 days after naloxone treatment, put in aprotinin-pre-cool tube, mixed evenly, and centrifuged at hypothermia. Plasma was maintained in refrigerator at - 70 ℃. The kit was provided by Neurobiology Department of Shanghai Second Military Medical University of Chinese PLA. Concentration of plasma β-endorphin was measured by using radio-immunity assay.All data were expressed as Mean ± SD and results were compared with paired t test. MAIN OUTCOME MEASURE： Concentration of plasma β-endorphin. RESULTS： All 97 neonates were involved in the final analysis. Concentration of plasma β-endorphin in neonates with severe asphyxia was lower after treatment as compared with that before treatment, and there was significant difference （t = 10.31, P 〈 0.01 ）. CONCLUSION： Naloxone can decrease level of plasma β-endorphin in neonates with severe asphyxia.
文摘We evaluated the effects of β-endorphin (β-EP) antiserum administrated intravenously and intracisternally on the ischemic arrhythmia induced by coronary ligation in SD rats. It was found that β-EP antiserum given intracisternally but not intravenousllyreduced the severity of ischemic arrhythmia. These results indicate that central β -EP may be involved in the mechanisms of ischemic arrhythmia.
文摘Endorphins are the body's natural opioids that are created and released by the central nervous system, hypothalamus and pituitary gland. Endorphins have a reputation for pain reduction, enhancing excitement or satisfaction, boosting confidence, enabling control of emotions and generating feelings of euphoria, and are involved in the natural reward cycle. There is also evidence in the literature suggesting the role of endorphins in sexuality(including sexual function and sexual behaviours), as they may regulate the release of sex hormones, prolactin and growth hormone, which are involved in sexual function and love. Endogenous oxytocin is another intrinsic hormone whose role in inducing labour contractions, the delivery of the baby and stimulating lactation has been well studied. However, the potential impact of endorphins and oxytocin on sexuality and romantic relationships is not well understood. This article reviews the research on endorphins and endogenous oxytocin and how they relate to human sexuality and romantic relationships. Some animal studies report the effect of endorphin and oxytocin on sex hormones and mating behaviours, but these findings have not been supported by research into human behaviour, indicating many gaps in knowledge relating to the association between these hormones and human sexuality.
文摘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.
文摘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.
文摘BACKGROUND： Several studies have confirmed that endothelin and endorphin are involved in the occurrence of cerebral vasospasm. However, the correlation of these factors to acute cerebral infarction-related risk factors needs to be confirmed. OBJECTIVE： To detect endothelin-1 （ET-1） and beta-endorphin （β -EP） levels in plasma of patients with acute cerebral infarction, and to analyze the correlations of these factors to smoking, alcohol abuse, hypertension, diabetes mellitus, diseased region, diseased degree, gender, and other factors related to acute cerebral infarction. DESIGN： A case-control observation. SETTING： First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine; Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University. PARTICIPANTS： Sixty-nine inpatients with acute cerebral infarction were admitted to the Department of Neurology, Second Affiliated Hospital of Sun Yat-sen University （March 2003-January 2004） and First Department of Neurology, Guangdong Hospital of Traditional Chinese Medicine （March July 2004） and recruited for this study. All 69 inpatients corresponded to the diagnosis criteria of acute cerebral infarction, formulated in the National Working Conference of Cerebrovascular Disease in 1998, and were confirmed as acute cerebral infarction by CT/MRI. The patient group consisted of 35 males [（644- 12） years old] and 34 females[ （674- 13 ） years old]. Among them, 9 patients were smokers, 7 were alcohol users, 48 had a history of hypertension, and 16 had a history of diabetes mellitus. CT/MRI examinations revealed that 35 patients presented with left focus sites, 11 with right ones and 23 with bilateral ones. Following attack, 24 patients had Barthel Index Scale grading 〈 40 points, 21 patients 40-50 points, and 24 patients 〉 60 points. An additional 59 healthy individuals, who received health examinations simultaneously, were included as controls. Among the control subjects, there were 37 males [（62±10） years old] and 22 females [（65±11） years old]. Among them, 7 patients were smokers, and 6 were alcohol users. All controls had no history of stroke, hypertension, or diabetes mellitus. Informed consents of laboratory measurements were obtained from all subjects, and this study was approved by the Hospital Ethics Committee. METHODS： ① Following admission, all subjects were scored by Barthel Index Scale （BIS） and Hamilton Depression Scale. Meanwhile, hypertension, diabetes mellitus, gender, smoking, drinking, and other conditions were recorded. CT/MRI examination was conducted to identify the focus site.②On the 2^nd day after admission, ET-1 and β -EP plasma levels were measured with an automatic ET-1 and β -EP analysis kit. MAIN OUTCOME MEASURES： ET-1 and β -EP plasma levels and their correlation to acute cerebral infarction-related factors. RESULTS： Sixty-nine patients with acute cerebral infarction, and an additional 59 healthy individuals participated in the final analysis. β ET-1 [（63.80±27.65） ng/L vs. （46.50±9.36） ng/L, P 〈 0.05] and β - EP [（94.18±33.94） mg/L vs. （51.87±23.43） mg/L, P 〈 0.05] levels of the patient group were obviously higher than respective values of the control group. ② The ET-1 and β -EP levels of patients with cerebral infarction did not correlate to hypertension, diabetes mellitus, BIS, depression, cerebral infarct focus, disease course, gender, smoking or drinking （P 〉 0.05）. CONCLUSION： The ET-I and β-EP levels of patients with acute cerebral infarction increased, but they were not obviously associated with disease course, blood pressure, blood glucose, BIS, or other common cerebral infarction-related factors.
文摘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.
文摘To observe plasm a β-endorphin (β-EP) and gonadotrophin releasing horm one (GnRH), hum an chorionic gonadotrophin (hCG), progesterone (P4) levelsin w om en w ith early threatened abortion and w ith a history of recurrent spontaneous abortions (RSA). Tw enty patientsw ith threatened abortion at7～8 w eeksof gestation w ere re- cruited, allof them had a history of 3 or m ore recurrentunexplained abortions. They w ere treated w ith psychologicalconsultation accompanied by traditionalChinese herbs. Blood samples w ere taken to m easure β-EP, GnRH, hCG and P4 levels by radioim - m unoassay (RIA). The treatm ents w ere continued till10～12 w eeks, blood w astaken during this period to compare changes in these peptides / horm ones. Tw enty norm al pregnantw om en at7～8 and 10～12 w eeksand 20 patientsw ith incompleteabortion at 10～12 w eeksw ererecruited for comparativestudies. Results: (1) In norm alpregnant w om en, plasm a β-EP, GnRH, hCGand P4 levelsat10～12 w eeksw ere significantly higher than thatat7～8 w eeks (P< 0.01). (2) In patients w ith threatened abortion and a history of RSA, plasm a β-EP levels at7～8 w eeks w ere significantly higher than those of norm al pregnantw om en (P< 0.01); on the contrary, plasm a GnRH, hCGand P4 levelsin these patientsw ere significantly low er than thosein norm alcases (P< 0.01). After treatm ent, 16 of the 20 patients succeeded in m aintaining their pregnancies, the levels of the four plasm a contents at10～12 w eeks w ere sim ilar to thosein norm alpregnantw om en (P> 0.05). (3) Plasm a β-EPlevelsin patientsw ith incomplete abortionsat10～12 w eeksw ere dram atically higher and GnRH, hCGand P4 levelsw ere low er than in norm alpregnantw om en (P< 0.01). β-EP m ightplay a role in the pathophysiology of spontaneousabortion.
文摘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.
文摘The effect of electromagnetic field on plasma β endorphin in 30 patients with migraine were studied in the experiment. All subjects received a 20 minute repetitive transcranial magnetic stimulation (Frequency 10Hz, Average intensity 8mT) per time, and the total experiment lasted 20 times. Before and after the experiment, the EEG and plasma β endorphin were tested. The results show that the level of plasma β endorphin in patients blood increased significantly from (73.486±26.002)mg/ml to (116.934±67.592)mg/ml (p<0.01), and the EEG average magnitude of the migraine patients were improved obviously from 41.77μV to 47.42μV.
