Beta-endorphin Concentrations Research Articles

The influence of a course of complex application of supravenous laser irradiation of blood and phototherapy on indicators of the neurohormonal status of patients with true eczema

BACKGROUND: In the pathogenesis of true eczema, an important place is occupied by stress, under the influence of which stimulation of the hypothalamus and brain stem occurs, as well as activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. Stress-induced secretion of neurotransmitters impairs the barrier function of the epidermis, slows wound healing, increases itching and inflammation, and suppresses immunity by changing the immune response of T-helper cells. AIM: Assessment of the severity of the corrective effect of a course of application of supravenous laser irradiation of blood and broadband medium-wave phototherapy on the blood levels of adrenocorticotropin, cortisol and beta-endorphin in patients with true eczema with a moderate form of the course. MATERIALS AND METHODS: The study was carried out with the participation of 120 patients with a moderate form of true eczema. Using simple fixed randomization, all patients were divided into 4 groups. The first group (control, n=30) received only basic drug therapy, including the use of detoxification, hyposensitizing, antihistamines and topical glucocorticosteroids. Patients of the second group (comparison group 1, n=30) additionally underwent a course of supravenous laser irradiation of blood. In the third group (comparison group 2, n=30), broadband medium-wave phototherapy was performed against the background of basic therapy. Patients of the fourth group (main group, n=30) in addition to basic therapy received a course of combined exposure to supravenous laser blood irradiation and phototherapy. The concentrations of adrenocorticotropin, cortisol and beta-endorphin were determined in the blood of patients twice (before the start of treatment and 1 month after the start of therapy) using ELISA. The clinical condition of patients in the groups was assessed by changes in the EASI index. Additionally, we studied the dynamics of the level of reactive and personal anxiety using the Spielberger–Khanin questionnaire. RESULTS: Positive dynamics of adrenocorticotropin, cortisol and beta-endorphin were noted only in the comparison groups and the main group, which proves the high efficiency of correction of the neurohumoral status of patients through a course of complex use of supravenous laser blood irradiation and broadband mid-wave phototherapy. Quantitative changes in the assessed parameters during complex therapy with therapeutic physical factors indicate a supra-additive version of their interaction, realized through different modalities, points of application and mechanisms for realizing the biological potential of physiotherapeutic effects. CONCLUSION: The results obtained convincingly prove the effectiveness of an additional course of use of supravenous laser irradiation of blood in combination with broadband medium-wave phototherapy when correcting the neuroendocrine status in patients with true eczema. The close correlation between neurohumoral indicators and clinical and psychological patterns of the disease proves the pathogenetic significance of the studied neuroendocrine indicators, which allows us to consider their dynamics as informative criteria for the effectiveness of the treatment.

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. PerspectiveIn 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.

Antimigraine Effects of Awei Wu Wei Pills, A Monk’s Medicine

The Mongolian medicine (Awei Wu Wei pills) was evaluated as a potential treatment for Hirschsprung’s migraine in a Sprague-Dawley rat model. The results of this study showed a dose-dependent decrease in the duration of ear redness and head scratching, two behavioral attributes of migraine. The mechanism involves inhibition of the c-Jun N-terminal kinase signaling pathway, leading to decreased calcitonin gene-related peptide and nitric oxide expression and reducing vasodilation, serotonin, dopamine, and beta-endorphin concentrations following administration of Awei Wu Wei pills. In conclusion, Awei Wu Wei pills demonstrate promising antimigraine effects.

Plasma marker ACTH, cortisol, and beta-endorphins profile on pregnant women as targeted marker of approach for antenatal depression

Background: Antenatal depression is a frequent mental disorder with much less attention, and most women remain undiagnosed. Altered hypothalamic-pituitary-adrenal (HPA)-axis function mediates maternal depressive symptoms and has been widely reported. The present research aimed to determine the plasma marker HPA-axis including Adrenocorticotropic hormone (ACTH), cortisol, and beta-endorphin, as a suitable representation of mental health in pregnancy by evaluating the psychometric properties. Methods: Therefore, we examined a case-control study of 216 Bontang pregnant women. Psychological measures were conducted during the 27th week of pregnancy, including the Patient Health Questionnaire-9 (PHQ-9) assessment and Depression Anxiety Stress Scale (DASS). Blood samples were collected for plasma ACTH, Cortisol, and beta-endorphins assay as a marker of the HPA axis profile. Data were analyzed Stata for Mac version 14 (StataCorp, USA). Results: our finding showed that DASS scores correlated with PHQ-9 (r=0.79), ACTH (r=0.22), and beta-endorphin (r=54). PHQ-9 score significantly related to ACTH (r=0.27), cortisol (r=0.36) and beta-endorphin (r=0.71). Women with the highest DASS score and PHQ-9 depression scores at 27 weeks of pregnancy had significantly lower baby birth weight (P=0.000) than those women whose stress improved to or normal state. Plasma ACTH, cortisol, and beta-endorphin concentrations were significantly higher in pregnant women with antenatal depression compared to normal pregnancy (p&lt;0.01). All effects remain without controlling unwanted pregnancy. Conclusion: Our study demonstrates a role for circulating ACTH in regulating maternal cortisol secretion and a significant correlation between the HPA-axis profile and antenatal depression at 27 weeks of pregnancy.

Low Level Laser Therapy in the Treatment of Temporomandibular Joint – (Short Review)

Temporomandibular disorder (TMD) is a collective term, characterized by symptoms involving muscles of mastication, TMJ and orofacial structures resulting from a dysfunction of the stomatognathic system. Temporomandibular disorders (TMDs) which considered the major cause of non-dental facial pain, involve a wide range of symptoms in masticatory muscles and temporomandibular joints (TMJ). Diagnosis is usually delayed due to the multifactorial etiology, and the lack of assessment devices and parameters. The Low-Level Laser LLLT is a noninvasive, quick and safe, non-pharmaceutical intervention that may be beneficial for patients with TMDs. However, the clinical efficiency of LLLT in the treatment of this kind of disorders is controversial. Low-level laser is considered a phototherapeutic alternative method, like the low-level laser, as an effective source for stimulating the anti-pain signals in the tissues due to their low-level waves and energies. The low-level lasers might cause the increased beta-endorphin content, decreased both bradykinin and histamine levels, and increased lymphatic flow to decreased inflammatory factors and the decreased pain-related factors. Conclusion: This review suggests that LLLT effectively relieves pain and improves functional outcomes in patients with TMD.

Функциональная активность звеньев стресс-реализующей и стресс-лимитирующей систем в условиях светового десинхроноза

The secretion of most hormones obeys biological cyclicity and, if it is violated, approaches to the level, that determines the development of pathological processes. To prevent them, it is important to take into account not only the effects of the stress-implementing system, but also the state of the components of the stress-limiting system. The lack of specificity about endocrine shifts under conditions of light desynchronosis determined the expediency of an experimental study of the hormonal status of stress systems. Research methods. The experiment was carried out on 48 white male rats, which was divided into 4 equal groups: control and three experimental. The 1st, 2nd and 3rd experimental groups of animals were under round-the-clock artificial lighting during 1, 10 and 21 days respectively. Animals of the control group (4th) were kept in natural light conditions. The activity of stress-limiting and stress-realizing systems was assessed by blood serum ELISA for the concentration of ACTH, melatonin, and beta-endorphin. In blood smears, the number of catecholamine granules per 100 erythrocytes was counted in 10 fields of view. Research results. On the 1st day of the experiment, there was an increase of catecholamines and ACTH, a decrease of beta-endorphin in comparison with the control values. The corticotropin of the 2nd and 3rd experimental groups underwent only slight fluctuations. The 10th day is also characterized by a statistically significant increase in the content of catecholamines in comparison with individuals of the control group. When assessing changes after 21 days of dark deprivation, a significant sharp increase in the concentration of catecholamines and a drop in the level of melatonin were noted. The discussion of the results. In the experiment, a phased development of hormonal changes in stress systems is observed, which corresponds to the stages of OSA, which is due to a violation of melatonin rhythms. The use of the L / L lighting model has a pronounced negative effect on the state of the body as a whole and leads to a breakdown of the mechanisms of the stress-limiting system. The results of the experiment allow us to conclude that light desynchronosis is a risk factor for pathologies of the neuroendocrine system, which necessitates a more detailed study of this topic in order to develop measures to prevent the development of stress and associated diseases of adaptation.

Fire needle plus cupping for acute herpes zoster: study protocol for a randomized controlled trial

BackgroundAcute herpes zoster (AHZ) is a common skin disease caused by invasion of the varicella zoster virus into the ganglia and skin, and the severe pain is the most complaint, which can seriously disturb the normal life of patients. Fire needle plus cupping is a special acupuncture treatment, which is widely used to treat AHZ for its better analgesic effect in China although it has not been fully verified by rigorous randomized controlled trial (RCT).Methods/designTo test the effect, a three-arm randomized parallel controlled trial protocol has been designed. A total of 105 AHZ patients suffering pain will be randomly divided into three groups in an equal proportion. The interventions are fire needle plus cupping (FC) in group A, famciclovir plus gabapentin (FG) in group B, and fire needle plus cupping plus famciclovir (FCF) in group C. The length for the trial is set for a week time frame. Precisely speaking, the A group (FC) is to carry out 1 treatment per day for the total of 7 treatment sessions within 1 week period. On the other hand, the B group (FG) will take drugs orally three times a day within the trial 1 week. Meanwhile, with its combination element, the C group (FCF) is due to undertake both treatments and drugs as prescribed for A and B groups within the trial week. As an intra-trial arrangement, analgesic medication will be carefully administered for temporary pain release if the sudden intolerable pain appeared. For the primary outcome, this study is due to apply visual analogue scale to identify pain intensity relief. As the secondary outcomes are concerned, this study is aiming to focus on the issues related to changes in substance P and beta-endorphin concentrations in peripheral plasma, as well as those issues of analgesic needs, side effects, symptoms, and physical signs including pain classification, local itching, burning sensation, fever, local lymphadenopathy, skin lesion area, blisters, herpes clusters, vesicular traits, ulcers, and pimples; all these are taken into account for evaluation. For the final stage, the participants are to be followed up for postherpetic neuralgia.DiscussionThe results of this trial aim to provide sufficient evidence on FC treatment over both FG and FCF treatments. It will then give a credible alternative treatment to cut down acute pain and to cure AHZ infection.Trial registrationChinese Clinical Trial Registry ChiCTR1800015372. Registered on 28 March 2018.

Aberrant pain modulation in trigeminal neuralgia patients.

Objectives The present study attempts to understand the role of supraspinal nociceptive pain modulation in typical trigeminal neuralgia (TN) patients by using a conditioned pain modulation paradigm and estimation of plasma levels of two important neuromodulators; Calcitonin Gene-Related Peptide andβ-endorphin. Methods Twenty TN patients and 20 healthy, age and gender-matched subjects participated in the study. The participants' hot pain thresholds (HPT) were measured over their affected side on the face. Testing sites were matched for healthy controls. For the conditioned pain modulation their contralateral foot was immersed in noxious cold (5°C) water bath (conditioning stimuli) for 30s and HPT (testing stimuli) was determined before, during and till 5min after the immersion. Plasma Calcitonin Gene-Related Peptide and β-endorphin levels were estimated to understand their role in disease pathogenesis and pain modulation. Results Change in HPT during foot immersion was significantly higher in healthy controls compared to TN patients (p<0.0001). The changes recorded in HPT in patients, were significant only in 2nd and 3rd minute post immersion. While in healthy controls, the effect lasted till the 4th minute. The concentration of beta-endorphin was significantly lower in TN patients (p=0.003) when compared to healthy controls. Conclusions The results suggest that there is an impairment in supraspinal pain modulation also known as Diffuse Noxious Inhibitory Controls in typical TN and that the reduced levels of β-endorphin may contribute to the chronic pain state experienced by patients.

Effect and safety of electroacupuncture analgesia at the latent stage of labor on the epidural analgesia

To investigate the effect of electroacupuncture (EA) analgesia at the latent stage of labor on epidural analgesia, labor outcome and neonatal score so as to provide the reference to the clinical labor analgesia. According to the random number table, 104 primipara of vaginal delivery were divided into three groups, named an EA group (37 cases), a sham-EA group (36 cases) and an epidural block group (31 cases). In the EA group, when the cervix opened up by 1 cm, Han's acupoint nerve stimulation apparatus was attached to bilateral Hegu (LI4) and bilateral Sanyinjiao (SP6) to achieve EA analgesia till the active stage (the cervix up 3 cm). In the sham-EA group, the procedure was same as the EA group, but with the sham-stimulation. In the epidural block, EA was not used in intervention. When the cervix opened up 3 cm, the epidural block and the patient-controlled epidural analgesia were all adopted in each group. The score of visual analogue scale (VAS) and the dosage of Sufentanil and Ropivacaine in patient-controlled analgesia pump at the different time points were compared among the groups. Respectively, in 1 h of EA stimulation (T1), 2 h of EA stimulation (T2), at the moment of epidural block (T3) and the complete open of the cervix (T6), the venous blood sample was collected to determine the concentration of beta-endorphin (beta-EP), and the use time of oxytocin, the bleeding amount and the state of newborn were recorded. There was no statistical difference in immediate of EA stimulation (T0) among the groups in VAS score (P>0.05). But, in T1 to T6, VAS score in the EA group was reduced obviously as compared with the sham-EA group and the epidural block group separately (P<0.05). There was no statistical difference in the use time of oxytocin among the three groups (P>0.05). In the sham-EA group and the epidural block group, bleeding amount during labor and in 24 h after labor was all higher than that of the EA group (P<0.05). In each group, the concentration of beta-EP in T3 and T6 was increased obviously as compared with that in T1 and T2 respectively (P<0.05). In the EA group, the concentration of beta-EP in T1 to T3 and in T6 was higher than that in sham-EA group and the epidural block group respectively (P<0.05). The dosage of Ropivacaine and Sufentanil in the EA group was less than that in either the sham-EA group or the epidural block group (P<0.05). There was no significant difference in amniotic fluid turbidity rate and Apgar score among the three groups (P>0.05). Electroacupuncture analgesia at the latent stage of labor effectively relieves labor pain of primipara, increases the concentration of beta-EP, enhances the effect of epidural block analgesia, reduces labor bleeding and has no side effect on newborn. The combination of electroacupuncture analgesia and the epidural anesthesia in the latent stage is applicable in the whole process of labor.

The effect of blood flow restriction exercise on exercise-induced hypoalgesia and endogenous opioid and endocannabinoid mechanisms of pain modulation.

This study aimed to investigate and compare the magnitude of exercise-induced hypoalgesia (EIH) with low-intensity blood flow restriction (BFR) resistance exercise (RE) at varying pressures to other intensities of resistance exercise and examine endogenous mechanisms of pain reduction. Twelve individuals performed four experimental trials involving unilateral leg press exercise in a randomized crossover design: low-load RE at 30% of one repetition maximum (1RM), high-load RE (70% 1RM), and BFR-RE (30% 1RM) at a low and high pressure. BFR pressure was prescribed relative to limb occlusion pressure at 40% and 80% for the low- and high-pressure trials. Pressure pain thresholds (PPT) were assessed before and 5 min and 24 h following exercise in exercising and nonexercising muscles. Venous blood samples were collected at the same timepoints to determine plasma concentrations of beta-endorphin and 2-arachidonoylglycerol. High-pressure BFR-RE increased PPTs in the exercising limb to a greater extent than all other trials. Comparable systemic EIH effects were observed with HLRE and both BFR-RE trials. PPTs in the exercising limb remained elevated above baseline at 24 h postexercise following both BFR-RE trials. Postexercise plasma beta-endorphin concentration was elevated during the BFR-RE trials. No changes to 2-arachidonoylglycerol concentration were observed. High pressure BFR-RE causes a greater EIH response in the exercising limb that persists for up to 24 h following exercise. The reduction in pain sensitivity with BFR-RE is partly driven by endogenous opioid production of beta-endorphin. BFR-RE should be investigated as a possible pain-modulation tool in individuals with acute and chronic pain.NEW & NOTEWORTHY High-pressure blood flow restriction (BFR) causes a greater hypoalgesia response in the exercising limb (48%) compared with light and heavy load resistance exercise (10-34%). Performing light load resistance exercise with BFR causes systemic hypoalgesia comparable with heavy load resistance exercise (10-18%). BFR resistance exercise prolonged the exercise-induced hypoalgesia response for 24 h in the exercising limb (15% and 24%, respectively). Activation of endogenous opioid production and a conditioned pain modulation effect partly mediate the relationship between exercise and hypoalgesia.

Clinical trials of acupuncture treatment of post-stroke shoulder pain

To observe the clinical therapeutic effect of "Tiaoshen Zhitong" (mental regulating and pain relieving) needling and its influence on serological indicators in the treatment of post-stroke shoulder pain, so as to provide new therapeutic thoughts and approach for post-stroke shoulder pain. A total of 80 inpatients with post-stroke shoulder pain were randomly divided into a control group (routine needling, 39 cases) and an observation group ("Tiaoshen Zhitong" needling, 41 cases) according to the random number table. Patients of the two groups accepted basic medication treatment including anticoagulants, hypotensive drugs, hypoglycermic drugs, lipid-lowering drugs, etc. In addition, patients of the control group were also treated by routine acupuncture stimulation (uniform reinforcing-reducing stimulation) of Jianyu (LI15), Jianqian (EX-UE12), Jianhou (Extra), Jianliao (TE14), Waiguan (TE5) and Hegu (LI4) on the affected side, and those of the observation group also treated by "Tiaoshen Zhitong" needling of Ear-Shenmen (MA-TF1), bilateral Neiguan (PC6, lifting-thrusting-reducing method), Shuigou (GV26, lifting-thrusting-reducing method), and Jianyu (LI15), Jianliao(TE14), Jianzhen (SI9) and Yanglingquan (GB34, the latter 4 points were stimulated with uniform reinforcing-reducing method) on the affected side. The treatment was given once every day, 6 days a week for 4 weeks. The pain severity was assessed by using visual analogue scale (VAS), the upper limb function evaluated by using Fugl-Meyer assessment (FMA) scale, the shoulder-joint function evaluated by using Constant-Murley score (CMS) questionnaire, and the daily living ability assessed by using Barthel index (BI) scale. The enzyme linked immunosorbent assay (ELISA) was used to determine the contents of serum beta-endorphin (β-EP), enkephalin (ENK) and dynorphin (Dyn). The clinical therapeutic effect was evaluated by using Nimodipine scale method. Of the 39 and 41 cases in the control and observation groups, 7(17.95%) and 12(29.27%) were basically cured, 12(30.77%) and 13(31.71%) experienced marked improvement, 8(20.51%) and 11(26.83%) were effective, 12(30.77%) and 5 (12.19%) failed, with the total effective rate being 69.23% and 87.80%, respectively. The effective rate of the observation group was significantly higher than that of the control group (P<0.05). After the treatment, the VAS score was obviously reduced (P<0.01), and the scores of FMA scale, CMS questionnaire and BI scale, and contents of serum β-EP, ENK and Dyn were all increased obviously in the two groups compared with their own pre-treatment (P<0.01). The therapeutic effect of "Tiaoshen Zhitong" needling was significantly superior to that of the routine needling in lowering VAS, and in raising scores of FMA scale, CMS questionnaire and BI scale and in up-regulating serum β-EP, ENK and Dyn levels (P<0.01). "Tiaoshen Zhitong" needling is effective in reducing post-stroke shoulder pain and improving the motor function of the upper limb and shoulder-joint as well as the quality of daily life in stroke patients with shoulder pain. Its analgesic effect is probably related to the increase of the levels of serum β-EP, ENK and Dyn.

Searching for an inhibitory action of blood-borne [beta]-endorphin on LH release

Concentrations of beta-endorphin were quantified in peripheral blood plasma of sheep by a radioimmunoassay that cross-reacted with beta-lipotrophin. Plasma concentrations of beta-endorphin increased abruptly after physical confinement, bacteraemia, and electroacupuncture treatment for induction of analgesia. In these experimental situations in which plasma concentrations of beta-endorphin increased, plasma concentrations of LH often decreased. To test the hypothesis that increases in blood-borne beta-endorphin actually caused the decrease in LH release, naloxone was administered to antagonize the opioid receptors at which blood-borne beta-endorphin might act. In no case did administration of naloxone disrupt the temporal correlation between experimentally induced increases in plasma beta-endorphin and decreases in plasma LH. It was concluded that the increases in blood-borne beta-endorphin did not cause the decrease in LH release. Other research investigated whether beta-endorphin might be delivered via blood from pituitary to hypothalamus in locally enriched concentrations. Even when pituitary release of beta-endorphin was acutely stimulated, it was not possible to demonstrate retrograde delivery of beta-endorphin to the hypothalamus without dilution in the systemic circulation. In conclusion, it is unlikely that blood-borne beta-endorphin inhibits the release of LH, and beta-endorphin should not be classified as a hormone until blood concentrations of the peptide can be shown to exert some effect at a location distant from its site of secretion.

Odor perception and hedonics in chronic schizophrenia and in first episode psychosis.

Background and purposeThe study evaluated olfactory performance and pleasantness rating of odors in patients with first episode psychosis (FEP) and chronic schizophrenia (SCH) with regard to the severity of psychopathological symptoms and plasma β-endorphin concentration.Patients and methodsTwenty patients with FEP, 27 with SCH and 29 healthy individuals, were recruited to the research . The University of Pennsylvania Smell Identification Test (UPSIT), subjective odor hedonic judgment and plasma levels of β-endorphin (BE) assay were performed in all participants.ResultsIndividuals with SCH revealed higher BE concentration than other study groups (P=0.000). All patients identified pleasant odors poorer than controls, however, SCH made more identification errors (P=0.000) than those with FEP. Moreover, participants with FEP rated pleasant odors as more pleasant than individuals with chronic schizophrenia and healthy controls (P=0.009). Nevertheless, higher β-endorphin level was related with lower scores in pleasant odor identification (Rs=−0.452; P=0.046) and more severe psychotic symptoms in FEP sample. Chronic schizophrenia patients did not demonstrate any relationship between symptom severity, odor identification performance and β-endorphin concentration. No relationship was found between BE concentration and hedonic judgment of the presented odors among all study groups. Chronically ill subjects identified odors significantly more poorly than those with first episode psychosis. Deficits in identifying pleasant odors might not be the only potential risk factor for undergoing chronic, recurrent schizophrenia. All patients subjectively overrated pleasant odors. Those with SCH and more severe negative symptoms made significantly more identification errors.ConclusionThe endogenous morphine system deregulation is observed in first episode psychosis as well as in chronic schizophrenia. In first episode schizophrenia higher beta-endorphin concentration is related to pleasant odor identification deficit.

A Novel Paradigm for Sacubitril/Valsartan: Beta-Endorphin Elevation as a Contributor to Exercise Tolerance Improvement in Rats With Preexisting Heart Failure Induced by Pressure Overload

BackgroundSimultaneous angiotensin receptor (AT1) blockade and neprilysin inhibition with the use of sacubitril/valsartan has been recently approved to treat patients with heart failure (HF). Therapeutic benefits of this therapy have been attributed to natriuretic peptide elevation and AT1 receptor blockade. However, that pharmacologic picture may not be complete. The aims of this study were to investigate the pharmacology of sacubitril/valsartan compared with sacubitril and valsartan alone and to examine their impact on peptides up-regulated by neprilysin inhibition, such as beta-endorphin. Methods and ResultsAn HF model was induced by pressure overload via constriction of the suprarenal abdominal aorta in rats. Sacubitril/valsartan (68 mg/kg), valsartan (31 mg/kg), sacubitril (31 mg/kg), or placebo was administered by daily oral gavage (starting 4 weeks after pressure overload onset and continued for 4 additional weeks; n = 8 in each group). Exercise tolerance testing was conducted using a rodent treadmill and hemodynamic assessments were conducted under anesthesia with the use of Millar left ventricular (LV) conductance technology. Pressure overload led to exercise intolerance by 4 weeks and to hypertension and LV dysfunction and remodeling by 8 weeks. Both sacubitril/valsartan and sacubitril elevated beta-endorphin levels, by 40% and 54%, respectively, and improved exercise tolerance, by 93% and 112%, whereas valsartan did not. Indices of LV dysfunction persisted with the use of sacubitril/valsartan and valsartan therapies and even deteriorated in sacubitril group. ConclusionsWhen added to valsartan, sacubitril increases beta-endorphin concentrations and improves exercise tolerance. These data suggest beta-endorphin elevation as a potential mechanism of action leading to improvement in exercise tolerance that is seen with sacubitril/valsartan. This therapeutic benefit is potentially independent from LV function.

The effect of naltrexone as a carboplatin chemotherapy-associated drug on the immune response, quality of life and survival of dogs with mammary carcinoma.

The objective of this study was to evaluate the effect of low-dose naltrexone (LDN) as a carboplatin chemotherapy-associated drug in female dogs with mammary carcinoma in benign mixed tumors (MC-BMT) after mastectomy and to assess its association with quality of life and survival rates. Sixty female dogs were included in this study, all of which had histopathological diagnosis of MC-BMT and were divided into three groups: G1 (control), consisting of animals submitted only to mastectomy with or without regional metastasis; G2, composed of treated animals that did not present with metastasis; and G3, treated dogs that presented with metastasis. G2 and G3 were also subdivided according to the treatment administered: chemotherapy alone (MC-BMT(-) C/MC-BMT(+) C) or LDN and chemotherapy (MC-BMT(-) C+LDN/MC-BMT(+) C+LDN). All animals were subjected to clinical evaluation, mastectomy, peripheral blood lymphocyte immunophenotyping, beta-endorphin and met-enkephalin quantification, and evaluation of survival rates and quality of life scores. The results showed higher serum concentrations of beta-endorphin and met-enkephalin, fewer chemotherapy-related side effects, and better quality of life and survival rates in the LDN-treated groups than in LDN-untreated groups (P < 0.05). Evaluation of clinical and pathological parameters indicated a significant association between the use of LDN and both prolonged survival and enhanced quality of life. These results indicate that LDN is a viable chemotherapy-associated treatment in female dogs with MC-BMT, maintaining their quality of life and prolonging survival rates.

Evaluation of Maternal and Fetal Stress Hormones During the Process of Birth

Objective: This study aims to determine whether mode of delivery is associated with the endocrine stress response in mother and newborn.Study Design: This prospective observational study was conducted with 86 women with a normal singleton pregnancy who delivered healthy infants between 37 and 41 weeks of gestation in a tertiary center. Study groups included; (1) women undergoing normal vaginal delivery with epidural anesthesia, (2) women undergoing vaginal delivery with immersion in water for pain relief during labor, (3) women delivered through elective caesarean section without labor. After delivery, thyroid stimulating hormone, cortisol, insulin, prolactin and Beta-endorphin levels were measured in maternal and umbilical cord serum and their relationships between modes of delivery were investigated.Results: It was found that the concentrations of cortisol and beta-endorphin after vaginal delivery with immersion in water group in both mothers and infants were higher than other two modes of delivery and these differences were statistically significant. Umbilical cord concentration of cortisol was the lowest in the caesarean section group.Conclusions: Maternal and fetal stress response was found to be associated with the mode of delivery and labor.

Salivary beta-endorphin and substance P are not biomarkers of neuropathic chronic pain propensity

ObjectiveThe pathophysiology of chronic pain is complex, with most of our knowledge being derived from preclinical studies. The search for biomarkers mirroring the pathophysiology of chronic pain is ongoing, and there is an increasing interest in saliva as a diagnostic tool. Given what is known about salivary substance P and salivary gland innervation, we hypothesized that salivary substance P and/or beta-endorphin might reflect the basal activity of these neuropeptides in the central nervous system, thereby perhaps mirroring a general propensity to chronic pain. Based on this overall hypothesis, our aim was to compare salivary levels of these neuropeptides in chronic neuropathic pain patients with healthy controls. An additional aim was to relate salivary levels to plasma levels. Materials and methodsWe compared salivary concentrations of beta-endorphin and substance P in 14 chronic neuropathic pain patients with concentrations in 18 healthy controls using a Luminex technology kit. Salivary-to-plasma quotients were also calculated. ResultsWe found no significant difference between the groups' salivary concentrations of substance P and beta-endorphin. No correlation was found between salivary and plasma concentrations of each neuropeptide, which we hypothesize might point to local production of beta-endorphin and/or substance P in the salivary glands. Given high substance P salivary-to-plasma quotients, such a local production seems more likely for substance P than for beta-endorphin. ConclusionsPropensity to neuropathic chronic pain was not substantiated by our analysis of salivary levels of substance P and/or beta-endorphin. However, we report salivary-to-plasma quotients that give potentially important physiological insight about these neuropeptides.

Beta endorphin in serum and follicular fluid of PCOS- and non-PCOS women

PurposeTo compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters.MethodsFifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol.ResultsThere was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels.ConclusionBeta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.

Overrated hedonic judgment of odors in patients with schizophrenia.

The odor identification ability and its hedonic judgment in patients with schizophrenia were evaluated in the study. The association between olfactory performance and negative symptoms and β-endorphin concentration was also analyzed. Study groups consisted of 23 patients with negative symptoms (PN) and 25 without predominant negative symptoms (PP) and 21 healthy individuals. The University of Pennsylvania Smell Identification Test, odor hedonic evaluation, and plasma concentrations of β-endorphin assay in all participants were performed. PN perceived the poorer olfactory identification; nevertheless, they evaluated unpleasant odors as more pleasant than PP and controls. Beta-endorphin concentration was significantly higher among PN than in other study groups. No association was observed between β-endorphin and odors identification and odor hedonic judgment among all study groups. There is potential relationship between increased β-endorphin concentration and severity of negative symptoms. Patients with predominant negative symptoms tend to evaluate odors as significantly more pleasant. Individuals with this subtype of schizophrenia might present specific, altered pattern of smell identification and hedonic judgment. Presumably, β-endorphin has no direct influence on olfactory identification performance and hedonic judgment in schizophrenia.

Por qué la infusión preventiva de una dosis baja de sulfato de magnesio influye en la percepción del dolor postoperatorio y el nivel sérico de beta-endorfinas en las histerectomías abdominales totales

ObjectiveDue to the known role of preventive low dose magnesium sulphate on postoperative pain management, in this randomized, double-blinded, placebo-controlled study, we tried to investigate the possible relationship between low dose intra-operative magnesium sulphate infusion, postoperative analgesia and the level of serum beta-endorphin during total abdominal hysterectomy under general anesthesia. MethodsForty women undergoing total abdominal hysterectomy were randomly allocated into 2 groups (20 in each arm). Fifteen minutes before induction of anaesthesia, the case group received a continuous intravenous infusion of magnesium sulphate (15mg/kg/h) and placebo control group received the same volume of isotonic saline. Pain scores were assessed at 0, 6, 12, and 24h after operations using Verbal Numeric Rating Scale. Pethidine consumption was recorded precisely. Serum level of beta-endorphin just 15min before the induction and at the end of the operations was determined by ELISA technique. ResultsAt 6 and 12h after the operations, Verbal Numeric Rating Scale in the case group was significantly lower than that of placebo control group (P=.0001). Over 24h after the operations, pethidine consumption was significantly lower in the case group compared with control group (P=.0001). In the case group, serum level of beta-endorphin was significantly decreased at the end of the operations compared with before the induction (P=.04). ConclusionWe illustrated that preventive low dose intra-operative magnesium sulphate infusion reduces postoperative pain, has opioid sparing effect and declines serum beta-endorphin concentration during total abdominal hysterectomy.