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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: Alcohol use disorders (AUDs) are widespread, devastating and complex. About 20% of people who consume alcohol develop problem use, accounting for over 5% of worldwide deaths. While numerous animal models have facilitated understanding of the consequences of excessive drinking, translational models allow for experimental manipulation of factors thought to contribute to AUD liability. Methods: We employ a single-exposure conditioned place preference assay (SE-CPP) to investigate the influence of age, sex and the opioid peptide β-endorphin (bE) on the initial rewarding effects of ethanol, a strong predictor of AUDs. Adolescent (PND28-35) and adult (PND70-90) male and female, control C57BL/6J and bE-deficient mice were tested following a single injection of 1.5 g/kg of ethanol. Following the SE-CPP test, animals were deeply anesthetized, sacrificed, and perfused, and the brains were subsequently sectioned at 40 microns and processed for immunohistochemical localization of c-fos. One-sample, two-tailed t-tests were used to assess drug preference or aversion and the locomotor effects of alcohol. Results: In general, adults were more sensitive to the effects of alcohol than adolescents, and outcomes depended on sex and bE. For example, among females, adolescents were stimulated by the drug, but insensitive to locomotor effects as adults, while among males, adolescents were insensitive and adults sedated. Wild-type adolescents of both sexes failed to evince initial subjective reward from the drug, but bE-deficient adolescents, and all adult subjects, preferred a context once associated with ethanol over one that had been paired with saline. c-fos immunoreactivity in multiple brain regions was attenuated in bE-deficient animals, though influences of both sex and bE grew stronger with age. Conclusions: This study demonstrates the utility of the SE-CPP paradigm for elucidating factors that contribute to the liability for AUDs, and supports the growing body of research that shows that sensitivity to the rewarding effects of alcohol changes during the course of development. Our results also suggest that developmental contributions are sex-dependent, and may also depend on the influence of endogenous opioid signaling. [ABSTRACT FROM AUTHOR]

Auricular acupuncture (AA) is becoming increasingly common in primary care clinics, emergency departments and peri-operatively for pain relief. Over the last decade, since the last comprehensive reviews were published, the literature has expanded. In this scoping review, we seek to document the efficacy of AA in treating both acute and chronic pain, describe the mechanism of action of AA in treating pain, and discuss how AA has been integrated into Western medicine to date. The authors performed a MEDLINE search inclusive of articles from 1966 to June 2023 including articles written in English identifying literature. We included human studies when more than 3 patients were included. Three hundred and fourteen unique articles were identified and 152 were selected by title screen. After abstract review, 117 were chosen for full-text review. Following full-text review, 33 articles were excluded and 21 added from references, totaling 105 articles included in our scoping review. AA reduces pain severity in patients with both acute and chronic pain. The best studies in the acute settings have occurred in the peri-operative setting where sham AA is employed, multiple sessions of AA are given, and medication dosing is carefully monitored. In these cases, AA reduced pain and post-operative medications. In patients with chronic pain, multiple sessions of AA resulted not only in pain relief but also in improvements in function and disability. Literature suggests that AA works through multiple mechanisms with the most compelling data coupled to the autonomic nervous system and neuroendocrine system. Curriculums designed to teach AA and aid in implementation have been published. AA is an accessible, effective means of pain relief. AA is relatively straightforward to learn, and protocols and curriculums exist to teach healthcare professionals this valuable skill. Overcoming implementation barriers, including patient education, are essential next steps. This review was written to analyze the current research on an increasingly popular pain relief treatment, auricular acupuncture. Auricular acupuncture has been an effective method of pain relief for patients with short-term pain. People who experienced pain after surgery and received auricular acupuncture experienced a decrease in pain and pain medications. Patients with chronic pain who underwent auricular acupuncture experienced pain relief and an increase in their functional abilities. Auricular acupuncture is thought to affect the body's autonomic nervous system and neuroendocrine system as it creates its source of pain relief for the body. Auricular acupuncture is increasingly popular in the education of healthcare workers and clinical practice. Research shows auricular acupuncture is an effective, easy, and less expensive method of pain relief, whose growth in pain management use may benefit from further education, especially for patients. [ABSTRACT FROM AUTHOR]

This paper addresses the conditions for the development of creativity and the possible obstacles along the way. It explores conscious and unconscious mechanisms which either impede or support this process. Creativity is seen as a special case of relationships between internal and external objects, with some aspects being more consistent and others being more fluid throughout an individual's life. This paper is based on the clinical experience of psychodynamic work with clients whose psychological predicaments related to creativity impoverished different areas of their lives. The non‐exhaustive list of factors to be considered when working with those clients includes a blocked epistemophilic instinct, excessively repressed aggression, and strong negative projections. A harsh superego opposing a weak 'internal supporter' combined with an internalised negative parental attitude to their own creativity constitutes a powerful unconscious force which prevents it from blossoming. A high level of basic anxiety, a low degree of omnipotence, and the release of endorphins in response to suffering contribute to these difficulties. Insufficient capacity to sublimate emotions and an inability to free associate prevent clients from finding the links between ideas born in the mind and their expression that could be accessed by others. [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]

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is β-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well. [ABSTRACT FROM AUTHOR]

Background & Objective: Studies have shown contradictory results regarding the use of pregabalin and melatonin as analgesic agents. Because the analgesic effects of these drugs as preemptive have not been compared in abdominal hysterectomy, one of the most common surgical procedures in women with moderate to severe pain, under general anesthesia. The aim of this study was to compare the pretreatment effects of melatonin and pregabalin on postoperative pain intensity in total abdominal hysterectomy (TAH). Materials & Methods: Ninety Patients were randomly divided into three groups (N=30): the first group received oral melatonin (6 mg), the second group received pregabalin (50 mg), and the third one who took no drug. Serum melatonin and betaendorphin levels were measured before and after the surgery. Pain intensity was assessed by the Numerical Rating Scale at 1,6,12, and 24 hours after the surgeries. Results: At 12 hrs after the surgery, mean pain intensity in the melatonin group was significantly lower than the pregabalin group, and in the pregabalin group was significantly lower than the third group (P<0.05). At 24 hrs after the TAH, the mean pain intensity in the melatonin group was significantly lower than the third group (P<0.05). Conclusion: injection preventive melatonin is more effective than pregabalin to reduce pain throughout the first 24 hrs after the TAH. [ABSTRACT FROM AUTHOR]

Naltrexone was first developed in 1963 as an opioid antagonist for therapeutic use in opioid-dependent individuals (alcohol, narcotics, and tobacco) with a 50 mg/day dose approved by the Food and Drug Administration (FDA). In 1985, Dr. Bernard Bihari explained that when naltrexone is taken in very low doses (1-5 mg/day) before bedtime, it blocks opioid receptors for 2-4 hours and leads to the release of endorphins in the early morning hours, serving as an opioid agonist and immunomodulatory agent. This extra endorphin secretion has been proven to enhance the immune system response in AIDS patients. Endogenous opioids that affect cell development are referred to as opioid growth factor (OGF) and metenkephalin (ME). Low-dose-naltrexone (LDN) pharmacotherapeutically possesses immunomodulatory, anticarcinogenic, antiviral, antibacterial, antiparasitic, and antifungal properties. LDN also increases the production and sensitivity of OGF, ME, and OGF receptor (OGFr) in the bloodstream, thereby enhancing quality of life. Based on these pharmacotherapeutic properties, LDN application is believed to be effective in the treatment or prophylaxis of various infectious diseases in cats and dogs, particularly vasculitis-related diseases such as feline infectious peritonitis (FIP) and infectious canine hepatitis (ICH), hypothyroidism, gastrointestinal disorders, spondylosis, rheumatoid arthritis, autoimmune diseases, pneumonia, atopic and allergic dermatitis, pyodermas, resistant pyodermas, methicillin-resistant Staphylococcus aureus (MRSA) or various gastrointestinal disorders, alopecia, stubborn dermatomycosis, stubborn demodicosis, various geriatric and oncogenic diseases, and deep depressions or obsessivecompulsive disorders. Thus, this review aims to evaluate the pharmacotherapeutic properties of LDN therapy usage and mechanisms of action in detail and assess the potential indications in cats and dogs based on these mechanisms. [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]

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. [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.

This study investigated the combined use of traditional Chinese medicine and Western medicine in the recovery process of a 36-year-old man who suffered from ischemic stroke. During the recovery period syncope, chest tightness, and sudden onset type A aortic dissection were noted after surgery. The author was a nurse of outpatient department of Chinese and Western medicine. From March 5 to May 21, 2020, three times a week, during the outpatient department, health problem such as physical dysfunction, constipation, and anxiety were assessed by physical assessment and four examinations of Chinese medicine. Based on the empirical literature on the combination of traditional Chinese medicine and Western medicine, a rehabilitation plan was developed that included the physical therapist and nurse. The traditional Chinese medicine acupoint pressing and foot bath were combined for the therapy. Head acupoint assisted with combs was used with the aim of promoting the secretion of endorphin. Constipation was improved by diet and health education. The patient's anxiety decreased from moderate to mild based on Baker Anxiety Scale scores. It is hoped that the combination of traditional Chinese and Western medicine can be helpful in clinical practice to improve the self-care ability of patients and to improve lower limbs muscle power. [ABSTRACT FROM AUTHOR]

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]

Music is a powerful emotional tool that can be used as an effective coping mechanism, as "medicine." Musical interventions are used in many areas of health care and medical sciences to meet the physical, psychological, social, and emotional needs of individuals. This article provides a theoretical definition of the concept of music as medicine: The use of music as a non-pharmacological strategy for coping and healing, based on its therapeutic properties, using a modification of Walker and Avant's method to identify antecedents, attributes, consequences, and empirical referents. Music as a coping strategy involves the use of music intervention and is an example of an emotion-focused, adaptive, coping strategy. The article concludes with a discussion of the implications of music as medicine for practice and research. Increased awareness of the concept of music as medicine as a strategy to manage stress offers an inexpensive non-pharmacological intervention to many organizations such as nursing care facilities, schools, and hospitals. [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]

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

EEG studies have suggested that cattle perceive pain when bled without stunning. The present study on bleeding without stunning, compared cows that had received a local anaesthetic on the site of the bleeding cut (Lurocaine; Luro cows) one hour before bleeding with a 35 cm knife, with cows that had not (saline: Placebo cows). Various physiological indicators potentially related to pain or stress were evaluated. Increases in heart rate (P < 0.02) and cortisol levels (P < 0.001) during slaughter, compared to control levels are indicative of slaughter stress in both groups. GSH/GSSG ratio, plasma PGE2, TNFα, and NO levels and blood haematocrit levels at slaughter were not influenced by slaughter or treatment. At bleeding, excluding two out of the 15 cows with non-missing data, Placebo cows presented a longer delay between the loss of the corneal reflex and respiratory arrest. Post-mortem, Longissimus muscle of Placebo cows had a faster pH decline and remained warmer. Overall, results suggest greater stress levels in this group, probably due to pain. Plasma or brain β-endorphin contents in relevant brain structures did not increase following bleeding in either group, thus not supporting the hypothesis that stress or pain-induced release of endorphins reduces pain perceived following the cut. Furthermore, according to existing knowledge, plasma β-endorphins do not reduce pain perceived. Thus, both our study and previous research do not provide evidence that slaughter without stunning does not cause pain or other forms of stress in at least part of the animals., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pharmacological investigations have substantiated the potential of bifunctional opioid/cannabinoid agonists in delivering potent analgesia while minimizing adverse reactions. Peptide modulators of cannabinoid receptors, known as pepcans, have been investigated before. In this study, we designed a series of chimeric peptides based on pepcans and morphiceptin (YPFP-NH 2 ). Here, we combined injections of pepcans and morphiceptin to investigate the combination treatment of opioids and cannabis and compared the analgesic effect with chimeric compounds. Subsequently, we employed computational docking to screen the compounds against opioid and cannabinoid receptors, along with an acute pain model, to identify the most promising peptide. Among these peptides, MP-13, a morphiceptin and pepcan-9 (PVNFKLLSH) construct, exhibited superior supraspinal analgesic efficacy in the tail-flick test, with an ED 50 value at 1.43 nmol/mouse, outperforming its parent peptides and other chimeric analogs. Additionally, MP-13 displayed potent analgesic activity mediated by mu-opioid receptor (MOR), delta-opioid receptor (DOR), and cannabinoid type 1 (CB1) receptor pathways. Furthermore, MP-13 did not induce psychological dependence and gastrointestinal motility inhibition at the effective analgesic doses, and it maintained non-tolerance-forming antinociception throughout a 7-day treatment regimen, with an unaltered count of microglial cells in the periaqueductal gray region, supporting this observation. Moreover, intracerebroventricular administration of MP-13 demonstrated dose-dependent antinociception in murine models of neuropathic, inflammatory, and visceral pain. Our findings provide promising insights for the development of opioid/cannabinoid peptide agonists, addressing a crucial gap in the field and holding significant potential for future research and development. PERSPECTIVE: This article offers insights into the combination treatment of pepcans with morphiceptin. Among the chimeric peptides, MP-13 exhibited potent analgesic effects in a series of preclinical pain models with a favorable side-effect profile., Competing Interests: Declaration of competing interest All authors confirm that this article content has no conflict of interest. We have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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]