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In modern times there is increasing acceptance that music-based interventions are useful aids in the clinical treatment of a range of neurological and psychiatric conditions, including helping to reduce the perception of pain. Indeed, the belief that music, whether listening or performing, can alter human pain experiences has a long history, dating back to the ancient Greeks, and its potential healing properties have long been appreciated by indigenous cultures around the world. The subjective experience of acute or chronic pain is complex, influenced by many intersecting physiological and psychological factors, and it is therefore to be expected that the impact of music therapy on the pain experience may vary from one situation to another, and from one person to another. Where pain persists and becomes chronic, aberrant central processing is a key feature associated with the ongoing pain experience. Nonetheless, beneficial effects of exposure to music on pain relief have been reported across a wide range of acute and chronic conditions, and it has been shown to be effective in neonates, children and adults. In this comprehensive review we examine the various neurochemical, physiological and psychological factors that underpin the impact of music on the pain experience, factors that potentially operate at many levels -- the periphery, spinal cord, brainstem, limbic system and multiple areas of cerebral cortex. We discuss the extent to which these factors, individually or in combination, influence how music affects both the quality and intensity of pain, noting that there remains controversy about the respective roles that diverse central and peripheral processes play in this experience. Better understanding of the mechanisms that underlie music's impact on pain perception together with insights into central processing of pain should aid in developing more effective synergistic approaches when music therapy is combined with clinical treatments. The ubiquitous nature of music also facilitates application from the therapeutic environment into daily life, for ongoing individual and social benefit. [ABSTRACT FROM AUTHOR]

Background: Skin is exposed to ultraviolet radiation (UV) and air pollution, and recent works have demonstrated that these factors have additive effects in the disturbance of skin homeostasis. Nuclear-factor-erythroid-2-related factor 2 (Nrf2) and aryl hydrocarbon receptor (AHR) appear to be appropriate targets in the management of combined environmental stressors. The protective effects of silymarin (SM), an antioxidant and anti-inflammatory complex of flavonoids, were evaluated. Methods: Reactive oxygen species (ROS) and interleukin 1-alpha (IL-1a) were quantified in UV+urban-dust-stressed reconstructed human epidermis (RHE) treated with SM. A gene expression study was conducted on targets related to AHR and Nrf2. SM agonistic activity on cannabinoid receptor type 2 (CB2R) was evaluated on mast cells. The clinical study quantified the performance of SM and cannabidiol (CBD) in skin exposed to solar radiation and air pollution. Results: SM decreased morphological alterations, ROS, and IL-1a in UV+urban-dust-stressed RHE. AHR- and Nrf2-related genes were upregulated, which control the antioxidant effector and barrier function. Interleukin 8 gene expression was decreased. The clinical study confirmed SM improved the homogeneity and perceived well-being of urban skins exposed to UV, outperforming CBD. SM activated CB2R and the release of β-endorphin from mast cells. Conclusions: SM provides protection of skin from oxidative stress and inflammation caused by two major factors of exposome and appears mediated by AHR-Nrf2. SM activation of CB2R is opening a new understanding of SM's anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Compared with the options available to human patients with cancer, treatment choices for dogs are often more limited. Chemotherapy is frequently the firstline treatment for many cancers. However, its efficacy can be limited, and its side effects can affect the quality of the remaining life. This paper briefly summarizes the experience with Viscum album L. (mistletoe) extract in human patients as a stipulation to consider treatment with mistletoe extract for canines with cancer. The mistletoe extract contains -among others - lectins and viscotoxins that have documented anti-proliferative effect on cancer cells as well as immunestimulatory function. Importantly, it also improves the well-being of patients with cancer due to its lectin ML-1 content, which can trigger the release of endorphins. Being cross-reactive with canine cells and having a relatively low side effect profile, it raises the question of whether mistletoe preparations might be considered as part of the treatment approach for dogs with cancer. [ABSTRACT FROM AUTHOR]

Background: Craniotomy aneurysm clipping is one of the main treatments for intracranial aneurysm (IA). Endotracheal intubation and intraoperative operation may induce dramatic hemodynamic fluctuations and increase the risk of aneurysm rupture. Intraoperative high-dose opioid use is the main measure to reduce the intraoperative stress response, but it increases the incidence of complications such as postoperative vomiting and delayed awakening. Transcutaneous electrical acupoint stimulation (TEAS) stimulates β-endorphin expression levels and reduces opioid requirements. In this study, we aimed to assess the effects of TEAS on remifentanil dosage and oxidative stress (OS) in craniotomy aneurysm clipping. Method: Forty-two patients with craniotomy aneurysm clipping were randomized into two groups: the TEAS group (T group) and the sham TEAS group (S group). "Hegu" (LI4), "Neiguan" (PC6) and "Zusanli" points (ST36) were selected, and a "HANS" percutaneous acupoint electrical stimulator was used for intervention 30 min before anesthesia induction until the end of the operation. The primary outcome was intraoperative remifentanil dosage. The secondary outcomes were intraoperative propofol dosage, mean arterial pressure (MAP) and heart rate (HR) 5 min before the TEAS intervention (T0), 5 min before head holder pinning (T1), immediately after pinning (T2), 5 min before craniotomy (T3), immediately after craniotomy (T4), at craniotomy (T5), and at the end of surgery (T6), as well as serum β-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100β, superoxide dismutase (SOD) and malondialdehyde (MDA) levels at T1, T2 and 24 h after surgery (T7). Results: The dosage of remifentanil in the T group was reduced compared to that in the S group (P < 0.05). At T2, T4 and T5, the MAP and HR in the T group were lower than those in the S group (P < 0.05). At T2 and T7, the levels of NSE, S100β and MDA in group T were lower than those in group S (P < 0.05), while the SOD levels in group T were higher than those in group S (P < 0.05). Conclusions: The use of TEAS can reduce the dosage of remifentanil and reduce hemodynamic fluctuations during craniotomy aneurysm clipping. It reduces the occurrence of OS and central nervous system damage during surgery and has a certain brain protective effect. Trial registration: ChiCTR2100052353. https://www.chictr.org.cn/about.html. [ABSTRACT FROM AUTHOR]

In modern times there is increasing acceptance that music-based interventions are useful aids in the clinical treatment of a range of neurological and psychiatric conditions, including helping to reduce the perception of pain. Indeed, the belief that music, whether listening or performing, can alter human pain experiences has a long history, dating back to the ancient Greeks, and its potential healing properties have long been appreciated by indigenous cultures around the world. The subjective experience of acute or chronic pain is complex, influenced by many intersecting physiological and psychological factors, and it is therefore to be expected that the impact of music therapy on the pain experience may vary from one situation to another, and from one person to another. Where pain persists and becomes chronic, aberrant central processing is a key feature associated with the ongoing pain experience. Nonetheless, beneficial effects of exposure to music on pain relief have been reported across a wide range of acute and chronic conditions, and it has been shown to be effective in neonates, children and adults. In this comprehensive review we examine the various neurochemical, physiological and psychological factors that underpin the impact of music on the pain experience, factors that potentially operate at many levels – the periphery, spinal cord, brainstem, limbic system and multiple areas of cerebral cortex. We discuss the extent to which these factors, individually or in combination, influence how music affects both the quality and intensity of pain, noting that there remains controversy about the respective roles that diverse central and peripheral processes play in this experience. Better understanding of the mechanisms that underlie music’s impact on pain perception together with insights into central processing of pain should aid in developing more effective synergistic approaches when music therapy is combined with clinical treatments. The ubiquitous nature of music also facilitates application from the therapeutic environment into daily life, for ongoing individual and social benefit.

Music is widely recognised as a human universal, yet there is no agreed explanation for its function, or why and when it evolved. I summarise experimental evidence that the primary function of musicking lies in social bonding, both at the dyadic and community levels, via the effect that performing any form of music has on the brain's endorphin system (the principal neurohormonal basis for social bonding in primates). The many other functions associated with music-making (mate choice, pleasure, coalition signalling, etc) are all better understood as derivative of this, either as secondary selection pressures or as windows of evolutionary opportunity (exaptations). If music's function is primarily as an adjunct of the social bonding mechanism (a feature it shares with laughter, feasting, storytelling and the rituals of religion), then reverse engineering the problem suggests that the capacity for music-making most likely evolved with the appearance of archaic humans. This agrees well with anatomical evidence for the capacity to sing. [ABSTRACT FROM AUTHOR]

Introduction and aim. Defects in the epidermal barrier, changes in sebum secretion and its composition, Malassezia spp. overgrowth, endocrine, immune, and neurological disorders are the main pathogenesis items of seborrheic dermatitis (SD). "The opioid system of the skin" was considered a new target in the diagnosis and treatment of SD. The study aimed to determine beta-endorphin (BE) levels in adult patients with seborrheic dermatitis and correlate them with the severity of symptoms and itching. Material and methods. 26 healthy and 62 SD people were examined. SEDASI scale were used to estimate the severity of symptoms and intensity of itching. The determination of the beta-endorphin level was carried out by the ELISA method with the test system Human BE NBP2 (78774 Novus Biologicals). Results. BE in the SD group was higher compared to the control group (35.5 pg/mL, 22. pg/mL, p<0.001). The level of BE in seborrheic patients did not depend on age and sex but was rising with severity of symptoms. Positive correlations were found between the level of BE and the SEDASI was 0.42 (p<.001), between the level of BE and itching was 0.332 (p=0.009). Conclusions. SD patients have an increased level of BE that positively correlates with itching and disease severity. [ABSTRACT FROM AUTHOR]

Anxiety is a common psychological symptom in expectant mothers, particularly among primigravidae during labor. There is a link between excessive anxiety and prolonged labor. One of the options to manage anxiety is the use of nonpharmacological methods. Numerous studies have investigated the effectiveness of auricular acupressure in treating anxiety, but few have examined its effect on anxiety biomarkers. Thus, the objective of this study was to analyze the effect of auricular acupressure targeting the Shenmen point on the levels of ß-endorphins and anxiety among primigravidae during the first stage of labor. This experimental study used a pretest-posttest control group design. The research subjects were primigravidae in the first stage of labor at the independent midwife practice of Yefi Marliandiani in Surabaya, Indonesia. Among 40 primigravidae, 34 individuals met the inclusion criteria and were then equally divided into treatment and control groups using a simple randomization. The treatment group received auricular acupressure at the Shenmen point every 30 minutes for a duration of 5 minutes each time, while the control group practiced deep breathing relaxation. The anxiety levels were assessed using the Hamilton Anxiety Rating Scale. The β-endorphin levels were measured by drawing 3 cc of venous blood before (4 cm cervix dilation) and after (9-10 cm cervix dilation) treatment. The obtained data were analyzed using paired- and independent-samples t-tests. A decrease in the mean anxiety level was observed in the treatment group (18.59±7.52) relative to the control group (19.76±7.11), albeit not significant (p=0.64). Simultaneously, the average β-endorphin levels of the treatment group (355.4±224.7) increased compared to the control group (225.1±127.5), with a significant difference observed between the two groups (p=0.04). In conclusion, while both auricular acupressure at the Shenmen point and deep breathing relaxation are effective in reducing anxiety, the former is more prominent in its ability to increase β-endorphin levels. [ABSTRACT FROM AUTHOR]

Music is widely recognised as a human universal, yet there is no agreed explanation for its function, or why and when it evolved. I summarise experimental evidence that the primary function of musicking lies in social bonding, both at the dyadic and community levels, via the effect that performing any form of music has on the brain’s endorphin system (the principal neurohormonal basis for social bonding in primates). The many other functions associated with music-making (mate choice, pleasure, coalition signalling, etc) are all better understood as derivative of this, either as secondary selection pressures or as windows of evolutionary opportunity (exaptations). If music’s function is primarily as an adjunct of the social bonding mechanism (a feature it shares with laughter, feasting, storytelling and the rituals of religion), then reverse engineering the problem suggests that the capacity for music-making most likely evolved with the appearance of archaic humans. This agrees well with anatomical evidence for the capacity to sing.

Throughout history humanity has searched for an optimal approach to the use of opioids that maximizes analgesia while minimizing side effects. This review reflects upon the conceptualization of the opioid receptor and the critical role that the pharmaceutical sciences played in its revelation. Opium-containing formulations have been delivered by various routes of administration for analgesia and other therapeutic indications for millennia. The concept of a distinct site of opium action evolved as practitioners developed innovative delivery methods, such as intravenous administration, to improve therapeutic outcomes. The introduction of morphine and synthetic opioids engendered the prevalent assumption of a common opioid receptor. Through consideration of structure-activity relationships, spatial geometry, and pharmacological differences of known ligands, the idea of multiple opioid receptors emerged. By accessing the high-affinity property of naloxone, the opioid receptor was identified in central and peripheral nervous system tissue. The endogenous opioid neuropeptides were subsequently discovered. Application of mu-, delta-, and kappa- opioid receptor-selective ligands facilitated the pharmacological characterization and distinctions between the three receptors, which were later cloned and sequenced. Opioid receptor signal transduction pathways were described and attributed to specific physiological outcomes. The crystal structures of mu, delta, kappa, and nociceptin/orphanin FQ receptors bound to receptor-selective ligands have been elucidated. Comparison of these structures reveal locations of ligand binding and engagement of signal transduction pathways. Expanding knowledge regarding the structure and actions of the opioid receptor fuels contemporary strategies for driving the activity of opioid receptors toward maximizing therapeutic and minimizing adverse outcomes.

Abstract Background Fibromyalgia is a form of chronic widespread pain that is defined as a syndrome of chronic symptoms of moderate to severe intensity, including diffuse pain, fatigue, sleep disturbance, cognitive impairment, and numerous somatic complaints. To date, there is no specific drug treatment for fibromyalgia but only symptomatic treatments. A drug free solution based on a wristband that emits millimeter waves associated with a therapeutic coaching program was developed. The application of millimeter waves on an innervated area has been described to have a neuromodulating effect, due to endorphin release stimulation and parasympathetic activation. Coaching is carried out to improve the patient’s adherence and to increase compliance and effectiveness of the treatment. Regular use of this solution by fibromyalgia patients is expected to improve sleep quality, reduce anxiety and pain levels, and, at the end, increase the quality of life. Methods This trial is performed over 8 French inclusion centers for a total of 170 patients. The effectiveness of the solution is evaluated according to the primary objective, the improvement of the quality of life measured through the dedicated Fibromyalgia Impact Questionnaire after 3 months. Patients are randomized in two groups, Immediate or Delayed. The Immediate group has access to the solution just after randomization in addition to standard care, while Delayed has access to the standard of care and waits for 3 months to have the solution. The purpose of this methodology is to limit deception bias and facilitate inclusion. The solution consists in using the device for three sessions of 30 min per day and four coaching sessions spread over the first 2 months of wristband usage. Discussion The objective is to confirm the effect of the integrative approach based on endorphin stimulation and a therapeutic coaching program in nociplastic pain and specifically for the patient suffering from fibromyalgia. If the effectiveness of the solution is demonstrated, we will be able to respond to the demand of fibromyalgia patients for access to an effective non-medicinal treatment to improve their quality of life. Trial registration ClinicalTrials.gov NCT05058092

The positive health of a person can be defined as the ability to live long in good health, possibly with no activity limitation. No method is yet available for its objective assessment in individuals, and we propose a framework in this communication that can operationalize this concept. Instead of distal factors, such as diet and lifestyle because these are subjective and difficult to measure, we concentrate on the objectively measurable biomarkers such as immunity level, endorphins, and handgrip strength. The focus is on the major parameters that may protect from diseases and infirmity and can be assessed by noninvasive methods. A combination of such parameters may signify positive health. This may be a novel way to measure positive health at the individual level. In this communication, we briefly review the literature and identify a few major biomarkers that provide a protective shield and could determine the status of positive health at the individual level. This exercise demonstrates that the assessment of the positive health of a person is feasible. A scale based on these and other relevant parameters can be developed later that could quantitatively measure the exact level of positive health. As the exact combination of the parameters that protects from ailments is not fully known yet, a framework such as this may help in identifying the data gaps that require attention in this context. The proposed framework may initiate a discussion on indicators of positive health and characterize the parameters for intervention that could increase a healthy life. [ABSTRACT FROM AUTHOR]

Chronic pruritus is one of the most common symptoms of dermatological diseases. It may occur in the course of other disorders, such as kidney disease. Chronic kidney disease-associated pruritus (CKD-aP) most often affects people with end-stage renal disease. The etiology of this condition is still not fully understood, but researchers are currently focusing on a thorough analysis of the association between disturbed opioid balance and increased neuronal signaling leading to pruritus. The aim of this study is to assess the concentration of endogenous opioids in dialysis patients with and without pruritus and in the control group, and to determine the correlation between the concentration of these substances and the occurrence and severity of itching. The study involved 126 dialysis patients and 50 healthy controls. Patients were divided into groups with pruritus (n = 62) and without pruritus (n = 64). The severity of pruritus was assessed using the NRS scale. The concentration of endogenous opioids was determined using the ELISA. The concentration of met-enkephalin was higher in the group of patients with pruritus compared to the control group. Moreover, significantly lower levels of β-endorphin and dynorphin A were observed in the group of dialysis patients compared to the control group. In addition, a statistically significant difference was seen between the β-endorphin concentration in the group of dialysis patients with pruritus compared to the group without pruritus. The ratio of β-endorphin/dynorphin A concentrations was significantly lower in the group of patients with pruritus compared to patients without pruritus and the control group. No correlations were found between serum level of studied opioids and the severity of pruritus. The concentrations of the studied opioids did not correlate with the severity of pruritus. Observed opioid imbalance may affect the occurrence of CKD-aP in dialysis patients, but a thorough understanding of the mechanism of action of these substances in the sensation of pruritus is necessary to assess the possibility of finding a new therapeutic target. [ABSTRACT FROM AUTHOR]

In anthropoid primates, social grooming is the principal mechanism (mediated by the central nervous system endorphin system) that underpins social bonding. However, the time available for social grooming is limited, and this imposes an upper limit on the size of group that can be bonded in this way. I suggest that, when hominins needed to increase the size of their groups beyond the limit that could be bonded by grooming, they co-opted laughter (a modified version of the play vocalization found widely among the catarrhine primates) as a form of chorusing to fill the gap. I show, first, that human laughter both upregulates the brain's endorphin system and increases the sense of bonding between those who laugh together. I then use a reverse engineering approach to model group sizes and grooming time requirements for fossil hominin species to search for pinch points where a phase shift in bonding mechanisms might have occurred. The results suggest that the most likely time for the origin of human-like laughter is the appearance of the genus Homoca 2.5 Ma. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'. [ABSTRACT FROM AUTHOR]

Opioids have been used for thousands of years for the treatment of pain. Records on papyri in Ancient Egypt reported the use of opium to relieve pain. In 1973, Candace Pert used radioactive morphine to assess its place of action and, surprisingly, found that the drug attaches to specific areas of the brain, namely on receptors called “morphine receptors”. Because animal model studies have debunked that a receptor would not be needed for the alkaloid in the Papaver somniferum plant, this finding sparked a search for the molecule that would endogenously stimulate that receptor, culminating in the discovery of “endogenous opiopeptides” or “endorphins” by John Hughes and Hans Kosterlitz in 1975. Most clinically relevant opioids operate at the level of the “morphine receptor” or “μ receptors”, and are therefore considered “agonists μ”. This paper looks at opioids in an effort to better understand the side effects and drug interactions. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia is a form of chronic widespread pain that is defined as a syndrome of chronic symptoms of moderate to severe intensity, including diffuse pain, fatigue, sleep disturbance, cognitive impairment, and numerous somatic complaints. To date, there is no specific drug treatment for fibromyalgia but only symptomatic treatments. A drug free solution based on a wristband that emits millimeter waves associated with a therapeutic coaching program was developed. The application of millimeter waves on an innervated area has been described to have a neuromodulating effect, due to endorphin release stimulation and parasympathetic activation. Coaching is carried out to improve the patient's adherence and to increase compliance and effectiveness of the treatment. Regular use of this solution by fibromyalgia patients is expected to improve sleep quality, reduce anxiety and pain levels, and, at the end, increase the quality of life.Methods: This trial is performed over 8 French inclusion centers for a total of 170 patients. The effectiveness of the solution is evaluated according to the primary objective, the improvement of the quality of life measured through the dedicated Fibromyalgia Impact Questionnaire after 3 months. Patients are randomized in two groups, Immediate or Delayed. The Immediate group has access to the solution just after randomization in addition to standard care, while Delayed has access to the standard of care and waits for 3 months to have the solution. The purpose of this methodology is to limit deception bias and facilitate inclusion. The solution consists in using the device for three sessions of 30 min per day and four coaching sessions spread over the first 2 months of wristband usage.Discussion: The objective is to confirm the effect of the integrative approach based on endorphin stimulation and a therapeutic coaching program in nociplastic pain and specifically for the patient suffering from fibromyalgia. If the effectiveness of the solution is demonstrated, we will be able to respond to the demand of fibromyalgia patients for access to an effective non-medicinal treatment to improve their quality of life.Trial Registration: ClinicalTrials.gov NCT05058092. [ABSTRACT FROM AUTHOR]

Introduction: Low back pain (LBP) is the most common ailment in patients with lumbar spine osteoarthritis (OA). There are many methods to treat LBP, such as manual therapy, osteopathy, massage, physical exercise, and physical therapy. The most effective of these are manual therapy and exercises combined with physical procedures, such as whole body cryotherapy (WBCT). Whole body cryotherapy can induce various hormonal adaptations in patients with OA. This is probably the body's reaction to cold and stress. The purpose of the study was to evaluate the impact of WBCT on β-endorphins, cortisol and adrenaline release, as well as on LBP in patients with OA of the lumbar spine. Material and methods: The study group consisted of 30 patients with lumbar spine OA who underwent a series of WBCT combined with therapeutic exercises. Before and after the therapy each patient was examined using a visual analogue scale (VAS) and blood samples were collected for laboratory determinations (ELISA). Results: After WBCT, the decrease in LBP measured by VAS was statistically significant (p < 0.0001). The mean value of blood β-endorphin level increased after the therapy but the difference was statistically insignificant (p = 0.10). The mean value of the plasma level of cortisol after treatment increased and the difference was statistically significant (p = 0.0009). The plasma level of adrenalin after treatment increased slightly, but the difference was statistically insignificant (p = 0.08). Conclusions: Whole body cryotherapy combined with therapeutic exercises had a positive effect on LBP reduction in patients with OA. On the basis of these changes, processes that take place in the nervous and endocrine systems are a response to the stimuli of cold and stress. The mechanism of action of extremely low temperatures on the human body is still not fully understood. [ABSTRACT FROM AUTHOR]

Opioid therapeutics are excellent analgesics, whose utility is compromised by dependence. Morphine (1) and its clinically relevant derivatives such as OxyContin (2), Vicodin (3), and Dilaudid (4) are "biased" agonists at the μ opioid receptor (OR), wherein they engage G protein signaling but poorly engage β-arrestin and the endocytic machinery. In contrast, endorphins, the endogenous peptide agonists for ORs, are potent analgesics, show reduced liability for tolerance and dependence, and engage both G protein and β-arrestin pathways as "balanced" agonists. We set out to determine if marine-derived alkaloids could serve as novel OR agonist chemotypes with a signaling profile distinct from morphine and more similar to the endorphins. Screening of 96 sponge-derived extracts followed by LC-MS-based purification to pinpoint the active compounds and subsequent evaluation of a mini library of related alkaloids identified two structural classes that modulate the ORs. These included the following: aaptamine (10), 9-demethyl aaptamine (11), demethyl (oxy)-aaptamine (12) with activity at the δ-OR (EC50: 5.1, 4.1, 2.3 μM, respectively) and fascaplysin (17), and 10-bromo fascaplysin (18) with activity at the μ-OR (EC50: 6.3, 4.2 μM respectively). An in vivo evaluation of 10 using δ-KO mice indicated its previously reported antidepressant-like effects are dependent on the δ-OR. Importantly, 17 functioned as a balanced agonist promoting both G protein signaling and β-arrestin recruitment along with receptor endocytosis similar to the endorphins. Collectively these results demonstrate the burgeoning potential for marine natural products to serve as novel lead compounds for therapeutic targets in neuroscience research.

Introduction Endorphins have been associated with analgesia and pleasurable activities. However, the so-called “happy chemicals” are far more complex than initially thought. Research shows that their impact on human behavior is modulatory, with the main goal not being “happiness” but a “return to the most desirable state” – which can be highly context-dependent. Objectives Review of the modulatory functions of endorphins on human behavior and their possible implications in psychiatric conditions. Methods Pubmed search consisting of the MeSH terms “Endorphins”, “Opioid Peptides”, “Behavior”, and “Psychiatry”. Results Endorphins elicit pleasure via stimulation of the release of dopamine from the ventral tegmental area to the nucleus accumbens. They are known to be involved in analgesia and stress response and social interaction. Endorphins can be released in a multitude of circumstances that may seem contradictory – having both inhibitory and stimulating roles in appetite, sexual response, and memory– but are modulatory effects depending on what constitutes homeostasis in each context. Peripheral levels of endorphins have been found low in depression and post-traumatic stress disorder. In schizophrenia, studies suggest that peripheral levels are high during psychosis, low in chronic disease and that naltrexone seems to improve auditory hallucinations. Endorphins may also have a role as markers of treatment response. Conclusions Endorphins have a complex role in behavior and homeostasis. These molecules could have implications in psychiatry- given that they are part of our stress response and are released to promote a more “desirable state”. Their role as a marker of illness or response to treatment needs further investigation. Disclosure No significant relationships.

Introduction  Nasopharyngeal carcinoma (NPC) is the most common malignancy in the field of otorhinolaryngology, and chronic pain is identical with this malignancy. Pain therapy according to World Health Organization (WHO) recommendations is WHO 3-step analgesic ladder. Pain is subjective and related to the function of beta-endorphin hormone. Objective  Analyzing the relationship between the degree of pain and plasma endorphin levels in stage III–IV NPC patients before and after the administration of WHO 3-step analgesic ladder. Materials and Methods  The study design used pretest and posttest without control design. Participants were given WHO 3-step analgesic ladder therapy for 3 days. The participants then rated the pain scale using the visual analog scale (VAS) and plasma beta-endorphin levels in venous blood. The statistical test used the dependent t -test, Wilcoxon test, and Spearman test with p  < 0.05, confidence interval: 95%. Results  There were 14 stage-III NPC patients with moderate pain (78.57%) and 31 stage-IV NPC participants had moderate pain (83.87%; p  = 0.071). The VAS value in the moderate pain group before and after therapy was 82.22% and 66.67%, respectively (p  < 0.001). The values of plasma beta-endorphin levels before and after therapy were 74.89 ± 69.12 and 72.49 ± 75.53 pg/mL, respectively (p  = 0.647). Plasma beta-endorphin levels were −19.20 ± 37.72 pg/mL (mild pain), −4.76 ± 35.30 pg/mL (moderate pain), and −21.67 ± 6.27 pg/mL (severe pain; p  = 0.717). Conclusion  Pain levels in advanced NPC patients have decreased after the therapy, but plasma beta-endorphin levels have no significant difference. [ABSTRACT FROM AUTHOR]

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors. [ABSTRACT FROM AUTHOR]

The evolutionary cognitive science of religion rarely strays far from strong individualistic principles despite a deep interest in the adaptive social bonding functions of religion. This raises serious problems for recent Christian theology, which favors concrete relational conceptions of individual personhood. Here, I argue that the wider evolutionary study of religion can mitigate this individualism by embracing recent research suggesting that religion's social bonding functions might be explained as much through energetic, endorphin stimulating, synchronous rituals as through cognitive mechanisms that increase prosocial behavior. The brain opioid theory of social attachment provides a helpful framework for understanding the evolutionary significance of such rituals. A close examination of research into the social effects of synchronous activity, I argue, reveals the need for a theoretically pluralistic explanation of how religion facilitates sociality, the major components of which are readily interpreted in terms that recognize the inherent relationality of individual personhood. [ABSTRACT FROM AUTHOR]

Background: Labor pain feels tremendous, and only 2-4% of mothers low pain during labor. Heat therapy is a non-pharmacological method. The heat therapy is still conventional, and this study uses a relaxation belt with more stable, dry heat media, and comfortable. Objective: This study aims to develop and test a relaxation belt for efforts to reduce labor pain intensity and increase β-endorphin levels in the primigravida of the active labor phase. Method: This study Research and Development (R&D). It consisted of 5 stages; stage I (literature study), stage II (product development), stage III (expert validity and phase I trials), stage IV (product revision and final product), and stage V (phase II trials). Results: The relaxation belt has been created, it has been validity experts test and field trials. The result that the relaxation belt is more effective in reducing pain and increasing β-endorphin levels than warm water compress (mean different pain labor 2.40; p

Abstract Aim Sacubitril/valsartan is a first‐in‐class angiotensin receptor‐neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short‐term changes in serum endorphin (EP) values and their relation with patients' physical functioning after initiation of sacubitril/valsartan treatment. Methods and results A total of 105 patients with heart failure with reduced ejection fraction, who were candidates for sacubitril/valsartan treatment, were included in this prospective, observational, multicentre, and international study. In a first visit, and in agreement with current guidelines, treatment with angiotensin‐converting enzyme inhibitors or angiotensin receptor blocker was replaced by sacubitril/valsartan because of clinical indication by the responsible physician. By protocol, patients were reevaluated at 30 days after the start of sacubitril/valsartan. Serum levels of α‐ (α‐EP), γ‐Endorphin (γ‐EP), and soluble NEP (sNEP) were measured using enzyme‐linked immunoassays. New York Heart Association (NYHA) functional class was used as an indicator of patient's functional status. Baseline median levels of circulating α‐EP, γ‐EP, and sNEP were 582 (160–772), 101 (37–287), and 222 pg/mL (124–820), respectively. There was not a significant increase in α‐EP nor γ‐EP serum values after sacubitril/valsartan treatment (P value = 0.194 and 0.102, respectively). There were no significant differences in sNEP values between 30 days and baseline (P value = 0.103). Medians (IQR) of Δα‐EP, Δγ‐EP, and ΔsNEP between 30 days and baseline were 9.3 (−34 − 44), −3.0 (−46.0 − 18.9), and 0 units (−16.4 − 157.0), respectively. In a pre–post sacubitril/valsartan treatment comparison, there was a significant improvement in NYHA class, with 36 (34.3%) patients experiencing improvement by at least one NYHA class category. Δα‐EP and ΔsNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Δα‐EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. Conclusions These preliminary data suggest that beyond the haemodynamic benefits achieved with sacubitril/valsartan, the altered cleavage of endorphin peptides by NEP inhibition may participate in patients' symptoms improvement.

Study aim: The aim of this study was to examine the effects of an 8-week circuit-type resistance training program on performance changes and neurotransmitter disruptions induced by industrial opiate in previously addicted men.

Roger Guillemin discovered and characterized the hypothalamic factors that control anterior pituitary functions. He consequently demonstrated that these brain peptides regulate a large number of major body activities through neuroendocrine mechanisms. This especially include growth, fertility and reproduction, endocrine gland functions and stress. These seminal works paved the way to major applications in many fields of physiology and medicine for diagnosis, pharmacology and therapy, far beyond the initial discovery and properties of these molecules, including in cancerology, immunology, inflammation, drug addiction and behavior.

Background: Curcuminoids and acupressure have beneficial effects in reducing pain and inflammation in patients with osteoarthritis. However, only a few clinical trials are investigating biomarkers to prove this objectively., Objective: This study aims to investigate the effect of acupressure and curcuminoids on inflammatory markers and pain in older people with osteoarthritis genu., Methods: A randomized controlled trial (RCT) was conducted among older people with osteoarthritis. All participants were randomized to a group that received 30 mg of curcuminoids in turmeric extract capsules and acupressure (group 1) or a group that received a placebo and sham acupressure (group 2) for 3 weeks., Results: The study was approved by the research ethics board; ClinicalTrials.gov reviewed this protocol. The extracts were manufactured from May 2023 to June 2023. Participant recruitment was conducted in September and October 2023; a total of 72 participants aged 60 years or older participated, of whom 75% (n=54) were female. Data were analyzed in April 2024, and dissemination of results is expected by the end of 2024., Conclusions: Primary outcomes were assessed at baseline and after the intervention. Relationships were assessed with inflammatory markers, endorphin hormones, and blood level of cycloxygenase-2 hormone. Additionally, secondary outcomes included pain, ability to perform activities of daily living, and quality of life. The beneficial effects that may be found in this trial may be exceptionally relevant in clinical practice, justifying this scientific inquiry. The benefits of herbs and acupressure can be helpful as additional options in treating inflammation and pain in patients with osteoarthritis., Trial Registration: ClinicalTrials.gov NCT06105840; https://clinicaltrials.gov/study/NCT06105840., International Registered Report Identifier (irrid): DERR1-10.2196/54970., (©Srinalesti Mahanani, Nyoman Kertia, Ema Madyaningrum. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.06.2024.)

Purpose: This study aimed to comprehensively explore and elucidate the intricate relationship between exercise and depression, and focused on the physiological mechanisms by which exercise influences the brain and body to alleviate depression symptoms. By accumulating the current research findings and neurobiological insights, this study aimed to provide a deeper understanding of the therapeutic potential of exercise in the management and treatment of depression., Methods: We conducted a systematic review of the scientific literature by selecting relevant studies published up to October 2023. The search included randomized controlled trials, observational studies, and review articles. Keywords such as "exercise," "depression," "neurobiology," "endocrinology," and "physiological mechanisms" were used to identify pertinent sources., Results: Inflammation has been linked to depression and exercise has been shown to modulate the immune system. Regular exercise can (1) reduce the levels of pro-inflammatory cytokines, potentially alleviating depressive symptoms associated with inflammation; (2) help in regulating circadian rhythms that are often disrupted in individuals with depression; and (3) improve sleep patterns, thus regulating mood and energy levels., Conclusion: The mechanisms by which exercise reduces depression levels are multifaceted and include both physiological and psychological factors. Exercise can increase the production of endorphins, which are neurotransmitters associated with a positive mood and feelings of well-being. Exercise improves sleep, reduces stress and anxiety, and enhances self-esteem and social support. The implications of exercise as a treatment for depression are significant because depression is a common and debilitating mental health condition. Exercise is a low-cost, accessible, and effective treatment option that can be implemented in various settings such as primary care, mental health clinics, and community-based programs. Exercise can also be used as an adjunctive treatment along with medication and psychotherapy, which can enhance treatment outcomes.

Endorphins are endogenous peptides that play a role in the regulation of pain, behavior, neuroendocrine and autonomic functions. In our study, we aimed to investigate the role of β endorphins in these effects of midazolam and dexmedetomidine. In this experimental study, 36 rats were divided into 6 groups. Group 1: (control) (n=6): An average of 100-150μl CSF samples were obtained after general anesthesia was achieved. An intracardiac 3-4ml blood sample was then taken. Group 2: (sham) (n=6): intraperitoneal 1 mL saline was administered. For all other groups after general anesthesia; Group 3: (midazolam-1) (n=6): intraperitoneal 4mg/kg midazolam was administered. Group 4: (midazolam-2) (n=6): 12mg/kg midazolam was administered intraperitoneally. Group 5: (Dexmedetomidine-1) (n=6): Dexmedetomidine 50µg/kg was administered intraperitoneally. Group 6: (Dexmedetomidine-2) (n=6): Dexmedetomidine 150 µg/kg was administered intraperitoneally. CSF and plasma samples were taken with the same method. All samples were stored at -80 °C. No statistically significant difference was found between the levels of rat CSF β-endorphin. However, when the plasma ß-endorphin levels of rats were evaluated, there was a statistically significant difference between the groups. No difference was found between the levels of plasma ß-endorphin in the patients who received midazolam, while plasma ß-endorphin levels of 50 µg/kg with dexmedetomidine were found to be lower than the control group. However, the values of the 150 µg/kg dexmedetomidine group did not support this result. Different findings from both this study and in vitro and human studies; the number of subjects, the use of different drug doses, the differences in measurement times, the absence of control groups may be due to methodological differences, and more research is needed. [ABSTRACT FROM AUTHOR]

The C-tactile (CLTM) peripheral nervous system is involved in social bonding in primates and humans through its capacity to trigger the brain's endorphin system. Since the mammalian cochlea has an unusually high density of similar neurons (type-II spiral ganglion neurons, SGNs), we hypothesise that their function may have been exploited for social bonding by co-opting head movements in response to music and other rhythmic movements of the head in social contexts. Music provides one of many cultural behavioural mechanisms for 'virtual grooming' in that it is used to trigger the endorphin system with many people simultaneously so as to bond both dyadic relationships and large groups. Changes in pain threshold across an activity are a convenient proxy assay for endorphin uptake in the brain, and we use this, in two experiments, to show that pain thresholds are higher when nodding the head than when sitting still. [ABSTRACT FROM AUTHOR]

Background. Rheumatoid arthritis (RA) is a systemic immunodeficiency disease characterized by persistent synovial inflammation, pannus formation, and bone and cartilage destruction, resulting in joint malformations and function decline. Objective. The purpose of this study is to evaluate the effect of moxibustion on clinical symptoms and levels of pain-related indicators beta-endorphin (β-EP) and dynorphin (Dyn) in patients with RA and to explore the potential anti-inflammatory and analgesic mechanisms of moxibustion in RA treatment. Methods. A total of 64 patients with RA who met the inclusion criteria were randomly and equally classified into the control and treatment groups. The control group received conventional treatment (oral methotrexate, folate, or leflunomide prescribed for a long time). The treatment group was treated with moxibustion at ST36 (Zusanli), BL23 (Shenshu), and Ashi points with respect to the control group. Patients' clinical symptoms and routine inspection indexes (rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]) were recorded before and after treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), β-EP, and Dyn were determined by enzyme-linked immunosorbent assay (ELISA). The software SPSS24.0 was used for statistical analysis. Results. (1) Compared with the pretreatment result, both of the two groups' clinical symptoms and routine inspection indexes (RF, ESR, and CRP) improved (P < 0.05), and the improvement of clinical symptoms in the treatment group outperformed that in the control group (P < 0.05). (2) TNF-α and IL-1β levels decreased significantly in the treatment group after treatment (P < 0.01), while no significant difference was observed in the control group (P > 0.05). (3) β-EP and Dyn levels in the treatment group were significantly increased after treatment (P < 0.01, P < 0.01), but the control group showed no significant difference (P > 0.05, P > 0.05). It is worth mentioning that the serum TNF-α, IL-1β, β-EP, and Dyn levels between the two groups were significantly different after 8 weeks of treatment (P < 0.05). (4) Differences in the serum β-EP and Dyn levels in the patients of the treatment group were correlated with TNF-α and IL-1β levels after treatment, and the correlation was mainly negative (r < 0). Conclusion. Moxibustion can improve joint pain in patients with RA using conventional western medicine. One of the mechanisms may affect the serum β-EP and Dyn levels by downregulating the inflammatory factors to play an anti-inflammatory and analgesic role. [ABSTRACT FROM AUTHOR]

Background: Functional dyspepsia (FD) is a commonly encountered entity worldwide and is difficult to treat. Most of the treatment modalities have low-quality evidence for use, except for proton pump inhibitors. Aerobic exercise has been shown to improve the symptoms, but its direct effect on symptoms has never been studied. The objective was to study the effects of moderate aerobic exercise on symptoms of FD and to compare the effect of conventional treatment alone vs. exercise plus conventional treatment. Methods: Out of 112 patients, 72 were randomly divided into controls (conventional treatment; n=36) and experimental (aerobic exercise for 30 min per session, 5 times a week for 6 weeks with conventional treatment; n=36) groups. Both the groups were assessed on day 1 and at the end of 6 weeks, using Glasgow Dyspepsia Severity Score (GDSS), Depression Anxiety Stress Scales-42 (DASS-42), and visual analogue scale (VAS). Results: Pre-treatment GDSS, DASS-42, and VAS in the experimental group were significantly different as compared to the post-treatment scores (p=0.00019, p=0.0002, p=0.00019, respectively). Even in the control group, pre- and post-treatment GDSS, DASS-42, and VAS scores were significantly different (p=0.00019, p=0.0002, p=0.00019, respectively). However, on the head-to-head comparison of the 2 groups, scores at the end of 6 weeks were significantly different (p< 0.05), in favor of the experimental group. Conclusion: Aerobic exercise as an auxiliary therapy to conventional treatment has better outcomes in the functional well-being of dyspepsia. [ABSTRACT FROM AUTHOR]

Background: Pain is a major complaint in cancer patients and a global problem that requires medical attention, including pain in cervical cancer. Although pharmacotherapy has been used for the treatment of cancer pain, there are still around 40% cannot be treated only with pharmacotherapy. Objectives: To determine the effects of electroacupuncture (EA) on pain in stage III cervical cancer patients. Methods: Twenty-eight stage III cervical cancer patients were divided into two groups (14 treatments and 14 controls) with randomized control trial design. The treatment group received EA with a frequency of 2/20-25 Hz at points of ST36, SP6, LI4 and LR3 for 30 minutes, while the control group did not receive EA. Both groups were given paracetamol and codeine at the same dose. Assessment was carried out by measuring pain scale (VAS), plasma ß-endorphin levels, and quality of life/QoL (EORTC QLQ-C30) before and after therapy. Results: The average reduction in VAS in the treatment group (2.71 ± 1.14) compared to the control group (0.71 ± 1.33; p < 0.001), average increase in plasma ß-endorphin levels in the treatment group (88.57 ± 52.46 pg/ml) compared to the control group (12.86 ± 56.76 pg/ml; p = 0.001), and in QoL, there were significant differences in symptom improvement between the treatment and control groups in the domain of fatigue, pain, insomnia and overall QoL (p < 0.05). Conclusion: Medical therapy combined with EA decreased pain scale, increased plasma ß-endorphin levels, and improved the QoL for stage III cervical cancer patients. [ABSTRACT FROM AUTHOR]

Acute alcoholism (AAI) is a common emergency. Currently, there is a lack of preventive and therapeutic drugs with superior safety and efficacy. Curcuma longa, Panax ginseng, Pueraria lobata, Pueraria flower, and Hovenia dulcis Thunb., which are the components of compound turmeric recipe (CTR), are, respectively, used in China as adjuvant therapeutic agents for AAI and alcoholic liver injury, respectively. The purpose of this research was to investigate the effect of traditional compound turmeric recipe in anti-inebriation treatment and to identify its underlying mechanisms. The mice were administered with CTR mixture, and ethanol was subsequently given to mice by gavage. The effects of CTR on the righting reflex, 24-hour survival, drunken behavior, blood ethanol concentration, and pathological changes of liver are depicted. The activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were detected. Besides, the activities of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 (P450), superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver and the levels of β-endorphin (β-EP) and leucine enkephalin (LENK) in the brain were also measured. Our results demonstrated that CTR can increase the activities of ADH, ALDH, P450, and SOD and decrease the contents of TNF-α, IL-8, and MDA in the liver. In addition, it can decrease the activities of ALT, AST, and ALP in serum and β-EP and LENK activities in the brain. CTR showed effects on prevention of acute alcoholism, promoting wakefulness, and alleviating alcoholic liver injury, which were likely mediated by the above mechanisms. [ABSTRACT FROM AUTHOR]

The American National Institute for Mental Health (NIMH) has put out a set of research goals that include a long-term plan to identify more reliable endogenous explanations for a wide variety of mental health disorders (Insel, 2013). In response to this, we have identified a major symptom that underlies multiple mental health disorders – social bonding dysfunction. We suggest that endogenous opioid abnormalities can lead to altered social bonding, which is a symptom of various mental health disorders, including depression, schizophrenia and ASD. This article first outlines how endogenous opioids play a role in social bonding. Then we show their association with the body’s inflammation immune function, and review recent literature linking inflammation to mental health ‘immunophenotypes’. We finish by explaining how these immunophenotypes may be caused by alterations in the endogenous opioid system. This is the first overview of the role of inflammation across multiple disorders where we provide a biochemical explanation for why immunophenotypes might exist across diagnoses. We propose a novel mechanism of how the immune system may be causing ‘sickness-type’ behaviours (fatigue, appetite change, social withdrawal and inhibited motivation) in those who have these immunophenotypes. We hope that this novel aetiology can be used as a basis for future research in mental health.