Hemostatic mechanism of Jianpi Yiqi Shexue decoction in treatment of immune thrombocytopenia.

OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), ß-endorphin (ß-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, ß-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and ß-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and ß-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The ß-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the ß-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001). CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of ß-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.

Interactions Between Endocannabinoid and Endogenous Opioid Systems Prospectively Influence Postoperative Opioid Use in Pregnant Patients Undergoing Cesarean Delivery.

Both endocannabinoid (EC) and endogenous opioid systems are involved in nociceptive processing and may work together synergistically based on preclinical models. This study evaluated the interactive effects of preoperative beta-endorphin (BE) concentrations (a key analgesic endogenous opioid) in cerebrospinal fluid (CSF) and ECs (CSF and plasma 2-arachidonoylglycerol and plasma anandamide) on postoperative opioid use and pain intensity in a prospective cohort of n = 112 pregnant patients undergoing scheduled cesarean delivery. Maternal blood and CSF samples were collected preoperatively for BE and EC assays. Patients completed measures of outpatient opioid use (number of tablets used and days of use) and average pain intensity at 2 weeks postoperatively. Results of general linear model analyses controlling for maternal age, body mass index at time of delivery, and race revealed significant multiplicative interactions between EC and BE concentrations on number of opioid tablets used (based on pill count), days of opioid use, and total milligram morphine equivalents used in the 2-week follow-up period. Elevated preoperative plasma and CSF 2-arachidonoylglycerol predicted reduced outpatient opioid analgesic use, particularly for patients low in CSF BE. Similar analyses for pain intensity at 2-week follow-up indicated a significant interaction (P < .02) characterized by higher preoperative BE concentrations being associated with lower subsequent pain only for individuals with low preoperative plasma anandamide concentrations. Further exploration of interactions between EC and endogenous opioid inhibitory systems as they influence responses to opioid analgesics in other clinical pain populations may help guide the development of precision pain management approaches. PERSPECTIVE: In the postoperative setting of patients undergoing cesarean delivery, elevated ECs were linked to reduced outpatient opioid analgesic use in individuals who had low endogenous opioid concentrations in CSF. Further exploration of interactions between these 2 inhibitory systems as they impact responses to pain management interventions appears warranted.

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum ß-EP level in puerpera. / è •è¸é’ˆæ²»ç–—äº§åŽè ¹ç—›çš„ä¸´åºŠç–—æ•ˆåŠå¯¹äº§å¦‡è¡€æ¸ ß-EP水平的影响.

OBJECTIVES: To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (ß-EP) level in puerpera. METHODS: Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum ß-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups. RESULTS: At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), ß-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the ß-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05). CONCLUSIONS: Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum ß-EP level and the increase of pain threshold so that analgesia is obtained.

Prospective evaluation of cerebrospinal fluid levels of ß-Endorphin as a predictor of opioid use after scheduled cesarean delivery.

Background: Prior laboratory work indicates that lower endogenous opioid function is associated with greater analgesic and subjective responses to opioid analgesics. We evaluated whether lower preoperative cerebrospinal uid (CSF) levels of the analgesic endogenous opioid ß-Endorphin (BE) were associated with increased opioid use after cesarean delivery (CD). Methods: We enrolled 136 pregnant women without opioid use or chronic pain who were undergoing CD under regional anesthesia. Preoperatively, participants completed validated pain measures and biospecimens were collected to assess BE levels in plasma and CSF. Postoperatively, pain measures at 48 hours and 2 weeks postpartum were assessed. We evaluated the association between CSF BE levels and total opioid use (in morphine milligram equivalents; MMEs) using linear regression controlling for confounding factors (primary analysis). In secondary analyses, we examined: 1) associations between plasma BE levels and total opioid use, and 2) associations between CSF and plasma BE levels and secondary outcomes (inpatient versus outpatient opioid use, pain intensity). Results: Participants completed surveys with 100% response rate. The majority were non-Hispanic white (65%), college educated (58%), had private insurance (71%), and had a prior cesarean delivery (69%). Psychiatric diagnoses (depression or anxiety) were common, both currently (22%) and in the past (26%).The median total opioid use across the inpatient and 2-week postpartum follow-up period was 89.1 milligram morphine equivalents (IQR 25-138). Preoperative cerebrospinal uid ß-Endorphin levels were not associated with total opioid use (beta = -0.05, SE 0.45, p = 0.64). Similar findings were noted for plasma ß-Endorphin levels. cerebrospinal uid ß-Endorphin levels were only weakly correlated with plasma ß-Endorphin levels (r = 0.30, p < .01). Preoperative cerebrospinal uid and plasma ß-Endorphin levels were both positively associated with postpartum pain measures (cerebrospinal uid: at 48 hours, beta = 0.19, SE 0.16, p < 0.05; Plasma: at 48-hours, beta = 0.02, SE 0.03, p = 0.02, and at 2-weeks, beta = 0.27, SE 0.03, p < 0.01). Conclusions: Lower preoperative cerebrospinal uid levels of ß-Endorphin are not associated with increased opioid analgesic use after scheduled cesarean delivery. It is possible that unassessed variability in baseline opioid receptor sensitivity may have confounded ability to test associations between ß-Endorphin levels and opioid use outcomes.

Thermochemical Study of the Interaction of Cytosine and Uracil with Peptides in a Buffered Saline: Complex Formation with beta-Endorphin 30-31 (Human), L-Glutathion (Reduced) and α-L-Alanyl-L-Tyrosine.

The complex formation of uracil and cytosine with glycyl-L-glutamic acid (ß-endorphin 30-31), γ-L-glutamyl-L-cysteinyl-glycine (glutathione reduced), α-L-alanyl-L-tyrosine, and α-L-alanyl-α-L-alanine in a buffered saline has been studied using dissolution calorimetry. The values of the reaction constant, the change in Gibbs energy, enthalpy, and entropy were obtained. It is shown that the ratio of the enthalpy and entropy factors depends on the charge of the peptide ion, and the number of H-bond acceptors in the peptide structure. The contributions of interaction between charged groups and polar fragments, hydrogen bonding, and stacking interaction are discussed, taking into account the effect of solvent reorganization around the reactant molecules.

The Impacts of Supervised Exercise Intervention on Tobacco Withdrawal Symptoms.

This study examined a supervised moderate-intensity aerobic exercise programme's effectiveness in regulating the Tobacco Withdrawal Symptoms (TWS) during temporary abstinence. This was a single group, pre and post-quasi intervention study. Thirty daily smokers participated in an 8-week supervised moderate-intensity aerobic exercise programme. We assessed the TWS, smoking urge, mood and stress-pleasure related hormonal variables after the aerobic exercise intervention. The measurements were conducted after overnight abstinence at baseline, post-intervention (at week-8) and post-detraining (at week-10). TWS components, smoking urge and mood were found to improve. For hormonal variables, cortisol and beta-endorphin except adrenaline showed insignificant changes at post-intervention and de-training. The findings suggest moderate-intensity exercise might help in reducing withdrawal symptoms and its adverse effects. Thus, exercise is an effective adjunct treatment in a smoking cessation programme.

The effect of delayed umbilical cord clamping on the infant's beta-endorphin level, mother-infant attachment and breastfeeding.

OBJECTIVES: To examine the effect of delayed umbilical cord clamping on the infant's betaendorphin level, mother-infant attachment and breastfeeding. STUDY DESIGN: This study had an experimental design with a control group. The study was undertaken between October and December 2017 in a maternity hospital in the east of Turkey. In total, 107 pregnant women [55 in the experimental group (delayed cord clamping) and 52 in the control group (early cord clamping)] participated in the study. RESULTS: The beta-endorphin level in the umbilical cord was 775.80 ± 229.35 in the experimental group and 547.91 ± 290.01 in the control group, and the difference was significant (t = 4.492, p = 0.000). Similarly, the prolactin level in the umbilical cord was 174.26 ± 47.20 in the experimental group and 119.06 ± 47.74 in the control group, and the difference was significant (t = 6.012, p = 0.000). Mother-infant attachment and breastfeeding success were higher in the experimental group. CONCLUSIONS: Beta-endorphin and prolactin levels in the umbilical cord, mother-infant attachment and breastfeeding success were higher in the group which underwent delayed cord clamping.

Endogenous opiates and behavior: 2021.

This paper is the forty-fourth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2021 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonizts and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).

The Role of Beta-Endorphin in Food Deprivation-Mediated Increases in Food Intake and Binge-Eating.

Food deprivation and binge eating represent significant public health concerns. Previous studies have implicated that hypothalamic opioids are affected following food deprivation. However, the role of each opioid peptide is not fully understood. Therefore, we investigated the role of endogenous beta-endorphin in food deprivation-mediated increases in food intake and binge eating. Male mice lacking beta-endorphin and their respective controls were subjected to 24 h food deprivation and then were randomly assigned to receive a regular diet (RD) or a high-fat diet (HFD). After four to five weeks, animals were re-exposed to an HFD to assess if previous exposure to HFD would enhance binge-eating behavior. We report that food deprivation significantly increases food intake; however, beta-endorphin may not be involved in this process. In addition, our findings suggest that prior exposure to an HFD promotes binge-eating behavior in wildtype mice, and that these effects were modestly decreased in beta-endorphin knockout mice. Overall, our results support that beta-endorphin may play a modest role in mediating palatability-driven feeding, but not hunger-associated feeding. A better understanding of neural mechanisms involved in binge eating and deprivation-induced increases in food intake may inspire new prevention or treatment options to decrease the burden of eating disorders.

Ultrasound Stimulation Potentiates Management of Diabetic Hyperglycemia.

OBJECTIVE: Glucose homeostasis is the only way to manage diabetic progression as all medications used do not cure diabetes. This study was aimed at verifying the feasibility of lowering glucose with non-invasive ultrasonic stimulation. METHODS: The ultrasonic device was homemade and controlled via a mobile application on the smartphone. Diabetes was induced in Sprague-Dawley rats through high-fat diets followed by streptozotocin injection. The treated acupoint CV12 was at the middle of the xiphoid and umbilicus of the diabetic rats. Parameters of ultrasonic stimulation were an operating frequency of 1 MHz, pulse repetition frequency of 15 Hz, duty cycle of 10% and sonication time of 30 min for a single treatment. DISCUSSION: The diabetic rats exhibited a significant decrease of 11.5% ± 3.6% in blood glucose in 5 min of ultrasonic stimulation (p < 0.001). After the single treatment on the first day, third day and fifth day in the first week, the treated diabetic rats had a significantly small area under the curve of the glucose tolerance test (p < 0.05) compared with the untreated diabetic rats in the sixth week. Hematological analyses indicated that the serum concentrations of ß-endorphin were significantly increased by 58% ± 71.9% (p < 0.05) and the insulin level was increased by 56% ± 88.2% (p = 0.15) without statistical significance after a single treatment. CONCLUSION: Therefore, non-invasive ultrasound stimulation at an appropriate dose can produce a hypoglycemic effect and improve glucose tolerance for glucose homeostasis and may play a role as adjuvant therapy with diabetic medications in the future.

Assessment of Plasma-Endogenous Opioid Neuropeptide Levels and Psychometric Properties of Non-Suicidal Self-Injury in Adolescents.

OBJECTIVE: Non-suicidal self-injury (NSSI) is one of the most common mental health problems and growing public-health issues, coupled with a significant population-level burden among adolescents in both developed and developing countries. We aimed to assess the role of endogenous opioid system-emotion regulation circuitry in NSSI through measurement of plasma beta-endorphin (ß-EP), met-enkephalin (MENK) levels, and determination of psychometric features of Turkish adolescent subjects. METHOD: In this research, we measured plasma ß-EP and MENK levels of 49 adolescents with NSSI and 39 control subjects without NSSI between the ages of 12-18 years. All adolescent subjects were observed in the outpatient clinic, and their clinical and sociodemographic characteristics were examined. All subjects were assessed using the Brief Symptom Inventory (BSI) and Inventory of Statements About Self Injury (ISAS). RESULTS: Plasma ß-EP levels were statistically lower in adolescents with NSSI than control group, whereas there was no statistically significant difference in MENK levels. ß-EP levels showed a negative correlation with depression severity. The data obtained from BSI and ISAS were not found to be associated with both ß-EP and MENK levels, while subscale scores exhibited versatile correlations. CONCLUSION: Our findings supported the salient role of ß-EP in NSSI behavior. Also, decreased plasma ß-EP could be assessed as a reliable indicator for NSSI. However, it is possible that measurement of basal plasma levels of neuropeptides might also bring many confounders and could cause bias. Therefore, repeated measurements of plasma-endogenous opioid neuropeptides in a time-dependent manner-concomitant to engage of NSSI behavior-might give more reliable results.

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum β-EP level in puerpera / 中国针灸

OBJECTIVES@#To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (β-EP) level in puerpera.@*METHODS@#Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum β-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups.@*RESULTS@#At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), β-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the β-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05).@*CONCLUSIONS@#Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum β-EP level and the increase of pain threshold so that analgesia is obtained.

Exploring the role of the endogenous opiate system in the pathogenesis of anemia in an opiate receptor knock-out model of Restless Legs Syndrome.

Restless Legs Syndrome (RLS) is characterized by bothersome leg discomfort accompanied by an urge to move to obtain relief and symptoms are worse at night and on lying down. There is at least partial and temporary relief with activity. It is also an opioid responsive disorder, often accompanied by iron deficiency with or without anemia, and inflammation may be a precipitating factor in some cases. We created two in-vivo opiate receptor knock out mouse models of RLS - a triple opiate receptor knock-out mouse and a mu opiate receptor knock-out mouse. Both sets of animals were restless during the sleep period as is also true of RLS. Both of our knockout models showed statistically significantly decreased Hemoglobin and Hematocrit indicating anemia and both models showed statistically significant decreases in serum iron suggestive of either iron deficiency anemia or inflammatory anemia. The rest of the hematologic studies were not consistent enough to determine which of these two types of anemia was present in either model. An additional experiment in normal wild type mice showed a statistically significant decrease in serum iron when an opiate receptor blocker was used. To our knowledge this is the first demonstration that deficiency of endogenous opioids might play a role in the production of anemia. Our hypothesis is that an intact endogenous opiate system is necessary for red cell homeostasis. The presence of opioid receptors both on red blood cells and on various immunologically based white blood cells suggest mechanisms by which deficiency in the endogenous opiate system could cause anemia of either the iron deficiency or inflammatory types. The administration of opioid agonists or antagonists to iron deficient cultures of red blood cell precursors is a next step in determining the role of the endogenous opiate system in the maintenance of red cell homeostasis and in the possible prevention of iron deficiency or inflammatory anemia where iron dysregulation is key.

Sublingual buprenorphine/naloxone treatment is not affected by OPRM1 A118G and BDNF Va66Met polymorphisms, but alters the plasma beta-endorphin and BDNF levels in individuals with opioid use disorder.

The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn't have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner.

Evidence of alterations of Beta-endorphin levels and Mu-opioid receptor gene expression in bipolar disorder.

Despite the well-recognized effects of endogenous opioids on mood and behavior, research on its role in bipolar disorder (BD) is still limited to small or anecdotal reports. Considering that Beta-endorphins (ß-END) and Mu-opioid receptors (MOR), in particular, have a crucial activity in affective modulation, we hypothesized their alteration in BD. A cross-sectional study was conducted. We compared: (1) BD type I (BD-I) patients (n = 50) vs healthy controls (n = 27), (2) two BD-I subject subgroups: manic (MAN; n = 25) vs depressed (DEP; n = 25) subjects. Plasma levels of ß-END and MOR gene expression in peripheral blood mononuclear cells were analyzed using ELISA Immunoassay qRT-PCR. We found that subjects with BD exhibited a significant upregulation of MOR gene expression and a decrease of ß-END (p<0.0001 for both). MAN display higher MOR levels than DEP (p<0.001) and HC (p<0.0001). Plasma levels of ß-END were lower in DEP compared to MAN (p<0.05) and HC (p<0.0001). The main limitations are the cross-sectional design and the lack of a group of euthymic subjects. Although preliminary, our results suggest a dysregulation of the endogenous opioid systems in BD. In particular, both MAN and DEP showed a reduction of ß-END levels, whereas MAN was associated with MOR gene overexpression.

Increased Levels of Beta-Endorphin and Noradrenaline after a Brief High-Impact Multidimensional Rehabilitation Program in Multiple Sclerosis.

Finding new solutions for the management of multiple sclerosis (MS) is crucial: further research is needed to study the effect of non-pharmacological interventions on the symptoms and the course of the disease, especially on lifestyle. Benefits from a proper lifestyle are evident not only on a clinical level but also on immune and neuro-endocrine systems. A brief high-impact multidimensional rehabilitation program (b-HIPE) was proposed for a sample of people with MS (pwMS) with a medium level of disease disability. We tested the change on clinical parameters and quality of life (QoL) after participation in B-HIPE. We furthermore decided to measure beta-endorphin and catecholamines concentrations pre- and post-participation in the b-HIPE program, due to the relationship between these hormones and the immune system in neurodegenerative diseases. Our results showed that after the b-HIPE program, an improvement of clinical parameters and QoL occurred. Moreover, we found higher levels of beta-endorphin and noradrenaline after participation in the program. These findings highlight the importance of implementing lifestyle interventions in the clinical management of MS. Furthermore, we hypothesize that the B-HIPE program increased beta-endorphin and noradrenaline levels, helping to reduce the inflammation related to MS disease.

Altered levels of neurobiological biomarkers at the interface of depression and gestational diabetes mellitus in Asian Indian women.

AIM: Gestational diabetes mellitus (GDM) might predispose the mothers to depression. Studies have reported the role of biomarkers either in GDM or depression, but very few have examined them in GDM with depression. The present study profiled the circulating levels of brain-derived neurotrophic factor (BDNF), Beta Endorphin (BE) and nesfatin-1 in women with GDM (with and without depression). METHODS: 160 pregnant women at 24-28 weeks of pregnancy (NGT/GDM with & without depression, n = 40 each) were randomly selected from the ongoing STRiDE (STratification of Risk of Diabetes in Early pregnancy) study. Depression score was derived using PHQ-9 questionnaire and ELISA was used to quantify the biomarkers. RESULTS: Circulatory levels of BDNF, BE and nesfatin-1 were lower in GDM women with or without depression compared to NGT without depression, however, nesfatin-1 levels were higher in NGT with depression. Notably, GDM with depression had the lowest levels of BDNF and BE. Both BDNF and BE levels were negatively correlated with depression, 1 h and 2 h plasma glucose. Regression analysis confirmed that each standard deviation decreases in BDNF and BE were independently associated with higher odds of GDM with or without depression even after adjusting for potential confounders. CONCLUSION: Our study has identified altered levels of a panel of neurobiological biomarkers (BDNF/BE/nesfatin-1) in those with combined GDM and depression. BDNF/BE could be potential biomarkers to assess the higher risk of coexisting depression and GDM.

Transcutaneous electrical nerve stimulation effects on pain-intensity and endogenous opioids levels among chronic low-back pain patients: A randomised controlled trial.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a promising non-pharmacological modality for the management of chronic low back pain (CLBP), but its efficacy and mode of action have not been clearly established. OBJECTIVE: To evaluate the responses of plasma beta-endorphin (ßE), met-enkephalin (ME), and pain intensity (PI) among patients with CLBP exposed to TENS or sham-TENS. METHODS: This double-blind trial involved 62 participants (aged 53.29 ± 5.07 years) randomised into TENS group (frequency 100 Hz, burst-rate 2 Hz, burst-width 150 µs, intensity 40 mA, duration 30 min), and sham-TENS group. The PI and plasma concentrations of ßE and ME were measured at baseline, immediately (0 hr), 1 hr, 24 hrs, and 48 hrs post-intervention. Data were analysed using general linear model repeated measures, ordinal regression, one-way analysis of variance, Kruskal-Wallis test, independent and paired samples t-tests, Mann-Whitney U test, Wilcoxon signed-rank test, and Kendall's tau coefficient. RESULTS: There was a significant temporal difference in PI between groups, F (1, 58) = 18.83, p< 0.001; the TENS group had better pain relief. The relative analgesic effect of TENS started immediately after the intervention (median difference [M⁢D] =-3, p< 0.001), peaked at 1 hr (M⁢D=-4, p< 0.001), and worn out by 24 hrs (M⁢D=-1, p= 0.029). However, there was no significant difference in ßE and ME between the groups from 0 hr to 24 hrs post interventions, and no significant correlation between the PI, and ßE, or ME. CONCLUSION: TENS significantly reduced PI up to 24 hrs after treatment.

αN-Acetyl ß-Endorphin Is an Endogenous Ligand of σ1Rs That Regulates Mu-Opioid Receptor Signaling by Exchanging G Proteins for σ2Rs in σ1R Oligomers.

The opioid peptide ß-endorphin coexists in the pituitary and brain in its αN-acetylated form, which does not bind to opioid receptors. We now report that these neuropeptides exhibited opposite effects in in vivo paradigms, in which ligands of the sigma type 1 receptor (σ1R) displayed positive effects. Thus, αN-acetyl ß-Endorphin reduced vascular infarct caused by permanent unilateral middle cerebral artery occlusion and diminished the incidence of N-methyl-D-aspartate acid-promoted convulsive syndrome and mechanical allodynia caused by unilateral chronic constriction of the sciatic nerve. Moreover, αN-acetyl ß-Endorphin reduced the analgesia of morphine, ß-Endorphin and clonidine but enhanced that of DAMGO. All these effects were counteracted by ß-Endorphin and absent in σ1R-/- mice. We observed that σ1Rs negatively regulate mu-opioid receptor (MOR)-mediated morphine analgesia by binding and sequestering G proteins. In this scenario, ß-Endorphin promoted the exchange of σ2Rs by G proteins at σ1R oligomers and increased the regulation of G proteins by MORs. The opposite was observed for the αN-acetyl derivative, as σ1R oligomerization decreased and σ2R binding was favored, which displaced G proteins; thus, MOR-regulated transduction was reduced. Our findings suggest that the pharmacological ß-Endorphin-specific epsilon receptor is a σ1R-regulated MOR and that ß-Endorphin and αN-acetyl ß-Endorphin are endogenous ligands of σ1R.

The Role of Beta-Endorphin in Cocaine-Induced Conditioned Place Preference, Its Extinction, and Reinstatement in Male and Female Mice.

Endogenous opioids have been implicated in cocaine reward. However, the role of each opioid peptide in this regard is unknown. Notably, the role of each peptide in extinction and reinstatement is not fully characterized. Thus, we assessed whether cocaine-induced conditioned place preference (CPP) and its extinction and reinstatement would be altered in the absence of beta-endorphin. We also examined if sex-related differences would exist in these processes. Male and female mice lacking beta-endorphin and their respective controls were tested for baseline place preference on day 1. On day 2, mice were treated with saline/cocaine (15 mg/kg) and confined to the vehicle- or drug-paired chamber for 30 min, respectively. In the afternoon, mice were treated with the alternate treatment and confined to the opposite chamber. Mice were then tested for CPP on day 3. Mice then received additional conditioning on this day as well as on day 4. Mice were then tested for CPP on day 5. Mice then received extinction training on day 9. On day 10, mice were tested for extinction and then reinstatement of CPP following a priming dose of cocaine (7.5 mg/kg). Male and female mice lacking beta-endorphin did not exhibit CPP following single conditioning with cocaine. On the other hand, only male mice lacking beta-endorphin failed to show CPP after repeated conditioning. Nonetheless, reinstatement of CPP was blunted in both male and female mice lacking beta-endorphin compared to controls. The present results suggest that beta-endorphin plays a functional role in cocaine-induced CPP and its reinstatement, and sex-related differences exist in the regulatory action of beta-endorphin on the acquisition but not reinstatement of cocaine CPP.