The impact of exercise on depression: how moving makes your brain and body feel better.

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.

Ketamine and major ketamine metabolites function as allosteric modulators of opioid receptors.

Ketamine is a glutamate receptor antagonist that was developed over 50 years ago as an anesthetic agent. At subanesthetic doses, ketamine and some metabolites are analgesics and fast-acting antidepressants, presumably through targets other than glutamate receptors. We tested ketamine and its metabolites for activity as allosteric modulators of opioid receptors expressed in recombinant receptors in heterologous systems and native receptors in rodent brain; signaling was examined by measuring GTP binding, b-arrestin recruitment, MAPK activation and neurotransmitter release. While micromolar concentrations of ketamine alone had weak agonist activity at mu opioid receptors, the combination of submicromolar concentrations of ketamine with endogenous opioid peptides produced robust synergistic responses with statistically significant increases in efficacies. All three opioid receptors (mu, delta, and kappa) showed synergism with submicromolar concentrations of ketamine and either Met-enkephalin, Leu-enkephalin, and/or dynorphin A17, albeit the extent of synergy was variable between receptors and peptides. S-ketamine exhibited higher modulatory effect compared to R-ketamine or racemic ketamine with nearly ~100% increase in efficacy. Importantly, the ketamine metabolite 6-hydroxynorketamine showed robust allosteric modulatory activity at mu opioid receptors; this metabolite is known to have analgesic and antidepressant activity but does not bind to glutamate receptors. Ketamine enhanced potency and efficacy of Met-enkephalin signaling both in mouse midbrain membranes and in rat ventral tegmental area neurons, as determined by electrophysiology recordings in brain slices. Taken together, these findings support the hypothesis that some of the therapeutic effects of ketamine and its metabolites are mediated by directly engaging the endogenous opioid system. Significance Statement We found that ketamine and its major biologically-active metabolites function as potent allosteric modulators of mu, delta, and kappa opioid receptors, with submicromolar concentrations of these compounds synergizing with endogenous opioid peptides such as enkephalin and dynorphin. This allosteric activity may contribute to ketamine's therapeutic effectiveness for treating acute and chronic pain and as a fast-acting antidepressant drug.

Tribute to Roger Guillemin, a pioneer in neuroendocrinology (1924-2024), Nobel Prize in Physiology or Medicine.

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.

Roger Guillemin a mis en évidence et caractérisé les facteurs hypothalamiques qui contrôlent les fonctions de l'adénohypophyse. Cette découverte majeure a permis de démontrer que ces peptides du cerveau régulent par voie neuroendocrine un grand nombre de fonctions importantes de l'organisme. C'est le cas de la croissance, de la fertilité et de la reproduction, des fonctions des glandes endocriniennes et du stress. Ces travaux pionniers ont ouvert la voie à des applications innovantes dans de nombreux domaines de la physiologie et de la médecine pour le diagnostic, la pharmacologie et la thérapie, bien au-delà de la découverte initiale et des propriétés de ces molécules. Ces domaines comprennent en particulier la cancérologie, l'immunologie, les problèmes inflammatoires, les addictions et le comportement.

The Foundational Science of Endogenous Opioids and Their Receptors.

The function of endogenous opioids spans from initiating behaviors that are critical for survival, to responding to rapidly changing environmental conditions. A network of interconnected systems throughout the body characterizes the endogenous opioid system (EOS). EOS receptors for beta-endorphin, enkephalin, dynorphin, and endomorphin underpin the diverse functions of the EOS across biological systems. This chapter presents a succinct yet comprehensive summary of the structure of the EOS, EOS receptors, and their relationship to other biological systems.

Pain, Fear, Anxiety, and Stress: Relations to the Endogenous Opioid System.

Pain, fear, stress, and anxiety are separate yet interrelated phenomena. Each of these concepts has an extensive individual body of research, with some more recent work focusing on points of conceptual overlap. The role of the endogenous opioid system in each of these phenomena is only beginning to be examined and understood. Research examining the ways in which endogenous opioids (e.g., beta-endorphin; ßE) may mediate the relations among pain, fear, stress, and anxiety is even more nascent. This chapter explores the extant evidence for endogenous opioid activity as an underpinning mechanism of these related constructs, with an emphasis on research examining ßE.

Endogenous Opioids and Exercise-Related Hypoalgesia: Modern Models, Measurement, and Mechanisms of Action.

This chapter will focus on the role exercise appears to have on activation and modulating factors within the central nervous system related to endogenous like opioids and its possible contribution to exercise-induced hypoalgesia. The implications for the exercise-mediated alterations of CNS activation factors related to opioids, specifically endorphins and enkephalins, will be presented. In this update, we discuss utilization of new technology and methods to monitor mechanisms of opioid involvement to suggest their contribution with exercise mediated hypoalgesia as well as their relationships to alterations of perceptions of pain and mood. Several special populations were included to suggest that not all individuals will respond to the exercise by mediating hypoalgesia. Factors that may confound the current understanding and suggestions from the recent literature will be presented as well as suggestions for future investigations.

Endogenous Opioids and Volunteering: On the Evolutionary Significance of Helping Others.

The human tendency to help others in need has been subject to trans-, inter-, and multidisciplinary studies (e.g., anthropology, neurobiology, evolutionary psychology, economy), within the frame of studying the mechanisms and adaptive significance of human prosocial behavior. Volunteering directed to unrelated and unfamiliar individuals is one common form of such helping behavior. Helping others may be adaptive for a species at a macro-level, which in turn is mediated by neurobiological mechanisms. A key target for analysis of the neurobiological underpinnings of volunteering is the endogenous opioid system (EOS). This chapter discusses EOS activity as a potential mediator of volunteering behavior. Evidence of the congruence between EOS involvement in social group behavior and social bonding and the role of these phenomena in volunteerism is reviewed. Models and empirical evidence of the mechanisms and adaptive value of helping unrelated others are discussed and integrated, including the mammalian caregiving system, the neurobiological model of prosocial behavior, synchrony promoting social bonding, and stress-driven motivation of prosocial action in immediate needs.

Physical Exercise as an Intervention for Depression: Evidence for Efficacy and Mu-Opioid Receptors as a Mechanism of Action.

Physical exercise is often cited as an important part of an intervention for depression, and there is empirical evidence to support this. However, the mechanism of action through which any potential antidepressant effects are produced is not widely understood. Recent evidence points toward the involvement of endogenous opioids, and especially the mu-opioid system, as a partial mediator of these effects. In this chapter, we discuss the current level of empirical support for physical exercise as either an adjunctive or standalone intervention for depression. We then review the extant evidence for involvement of endogenous opioids in the proposed antidepressant effects of exercise, with a focus specifically on evidence for mu-opioid system involvement.

Endorphins, Sexuality, and Reproduction.

Beta-endorphin is secreted from the hypothalamus and pituitary in both mother and newborn. The placenta produces numerous pituitary hormones from the third month of pregnancy, one of which is ßE. It has been suggested that ßE has a role in the appetitive and precopulatory phase of sexual behavior in animals. An increase in endorphin levels during sexual activity in humans may contribute to attachment and bonding between partners, but contradictory reports in the literature question the association between sexuality and ßE levels. The level of ßE also increases during pregnancy, rises in early labor, peaks in late labor, and drops in the postpartum period. This fluctuation provides natural analgesia, raises the pain threshold, decreases the sensation of pain, or suppresses pain, and decreases fear levels during labor and birth. Beta-endorphin also protects the fetus from hypoxia during labor and birth and potential neural damage by aiding blood flow to the brain under hypoxic conditions. It has been suggested that a variety of pharmacologic and nonpharmacologic complementary therapies, when used in pregnancy, labor, and birth, activate the opioid receptors in the CNS and alter the sensation of pain during labor and birth, affect the mother-child attachment and affect sexual function. These studies report contradictory results that will be discussed in this chapter.

The psychophysiology of music-based interventions and the experience of pain.

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.

Combination of Curcuminoids and Acupressure for Inflammation and Pain in Older People with Osteoarthritis Genu: Protocol for a Randomized Controlled Trial.

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.

A scoping review of mechanisms of auricular acupuncture for treatment of pain.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effectiveness of integrated approach of yoga therapy versus usual care in management on chronic low back pain patients: A randomized controlled pilot study.

BACKGROUND: Chronic low back pain is associated with both psychological and functional limitation. Yoga therapy has been shown to improve both the aspects. The present study was planned to evaluate integrated approach of yoga therapy with usaul care. AIMS: This controlled randomized trial was done to evaluate the clinical and molecular changes resulting from integrated approach of yoga therapy (IAYT) as an adjunct regimen and compared it with usual care for the management of chronic low back pain patients. MATERIAL AND METHODS: We enrolled 29 adult patients with non-specific chronic low back pain (CLBP). Patients were randomly divided into two groups. The control group received the usual care of treatment as per institutional protocol. The yoga group received IAYT as an adjunct to usual care. Primary outcomes were pain intensity assessed by verbal numerical rating scale (VNRS) and functional ability assessed by Modified Oswestry Disability Index (MODI). Secondary outcomes were pain catastrophizing, quality of life, fear of movement related to CLBP, type of pain, levels of ß-endorphin and TNF-α, and salivary CGRP. All parameters were measured at baseline, 1 and 3 months. RESULTS: A Significant decrease in VNRS score at 1 and 3 months was observed in both the groups with the yoga group showing a more significant reduction in pain over time than the control group (p = 0.036). MODI improved significantly only in the yoga group at 1 and 3 months. Intergroup comparison revealed significantly better MODI over time in the yoga group (p < 0.001). DN4, PDQ, PCS, HADS (anxiety), and Euro QOL had a statistically significant improvement at 1 and 3 months in the yoga group compared with the control group. The HADS (depression) had a statistically significant reduction scores in the yoga group at 3 months compared with the control group (p = 0.012). There was a significant reduction in TNF-α values in the yoga group compared with baseline (p = 0.004). CONCLUSION: IAYT therapy helped in addressing the psychological components of pain and improved quality of life patients with chronic low back pain compared with usual care.

The origins and function of musical performance.

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.

The opioid receptor: emergence through millennia of pharmaceutical sciences.

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.

Healer's High.

We explore the concept of healer's high, a phenomenon similar to runner's high. We define healer's high as a psycho-endocrine response of intense happiness and bliss, accompanied by a feeling of enhanced energy, experienced by health care professionals when they heal or help someone. We describe the endocrinology that underlies healer's high, and posit that this phenomenon may be used to enhance professional satisfaction, and mitigate compassion fatigue and burnout.

Beta Endorphins are not responsible for delayed gastric emptying of digestible solids after exercise in professional cyclists. A preliminary study / Las Beta endorfinas no son responsables del retardo del vaciamiento gástrico de sólidos en ciclistas profesionales tras el ejercicio. Un estudio preliminar

Objective: It has been reported that professional cyclists had an accelerated solid gastric emptying which decreased by increasing the exercise intensity. That could be explained by a predominance of stress-dependent motility inhibitors such gastrointestinal hormones, neurotransmitters and or the predominance of the gastric inhibitory vagal motor circuit. The aim of this preliminary study was to evaluate the role of β-endorphins, inhibitors of gastric motility, in these findings. Methods: Gastric emptying of solids marked with Tc99 while resting and plasmatic levels of β-endorphins were evaluated in 27 healthy controls and 19 professional cyclists (day 1). Besides, gastric emptying of solids was also assessed in cyclists when they reached 50% (day 1) and 75% (day 2) of the maximum oxygen consumption (low and high, respectively), during exercise on the cycle-ergometer. The third day, naloxone was administered in cyclists in order to block the β-endorphins receptors and gastric emptying was measured when they reached 75% of the maximum oxygen consumption. Results: Basal β-endorphin levels were lower in cyclists vs controls (p<0.05) and they increased with the exercise intensity (p<0.001). There were no significant differences in gastric emptying of solids with or without naloxone when 75% of the maximum oxygen consumption was reached. Conclusions: The inhibitory effect of the exercise in the gastric emptying of solids does not seem to be secondary to the action of β-endorphins, that leaves the gastric inhibitory vagal motor circuit a more likely predominant role.(AU)

Objetivo: Se ha informado de que los ciclistas profesionales tienen un vaciado gástrico sólido acelerado que disminuye al aumentar la intensidad del ejercicio. Esto podría explicarse por un predominio de los inhibidores de la motilidad dependientes del estrés, como las hormonas gastrointestinales, los neurotransmisores y o el predominio del circuito motor vagal inhibidor gástrico. El objetivo de este estudio preliminar fue evaluar el papel de las β-endorfinas, inhibidores de la motilidad gástrica, en estos hallazgos. Métodos: Se evaluó el vaciado gástrico de sólidos marcado con Tc99 mientras se evaluaban los niveles en reposo y plasmáticos de β-endorfinas en 27 controles sanos y 19 ciclistas profesionales (día 1). Además, también se evaluó el vaciado gástrico de sólidos en los ciclistas cuando alcanzaron el 50% (día 1) y el 75% (día 2) del consumo máximo de oxígeno (bajo y alto, respectivamente), durante el ejercicio en el cicloergómetro. El tercer día, se administró naloxona en los ciclistas para bloquear los receptores de β-endorfinas y se midió el vaciado gástrico cuando alcanzaron el 75% del consumo máximo de oxígeno. Resultados: Los niveles basales de β-endorfina fueron menores en los ciclistas frente a los controles (p<0,05) y aumentaron con la intensidad del ejercicio (p<0,001). No hubo diferencias significativas en el vaciado gástrico de sólidos con o sin naloxona cuando se alcanzó el 75% del consumo máximo de oxígeno. Conclusiones: El efecto inhibidor del ejercicio en el vaciado gástrico de sólidos no parece ser secundario a la acción de las β-endorfinas, lo que deja al circuito motor vagal inhibitorio gástrico un papel más probablemente predominante.(AU)

The Role of Asiatic Acid in Preventing Dental Pulp Inflammation: An in-vivo Study.

Purpose: Acute dental pulp inflammation necessitates early treatment to alleviate inflammation and pain. In the inflammatory phase, a substance is required to lower the inflammatory mediators and reactive oxygen species that play a crucial role in that phase. Asiatic acid is a natural triterpene obtained from the Centella asiatica plant with a high antioxidant value. This study examined the effect of Asiatic acid's antioxidant, anti-inflammatory, and antinociceptive properties on dental pulp inflammation. Methods: The research is an experimental laboratory, with a post-test only with a control group design. The study utilised 40 male Wistar rats weighing 200-250 grams and aged 8-10 weeks. Rats were divided into five groups (control, eugenol, Asiatic Acid 0.5%; 1%; 2% group). Dental pulp inflammation was created in the maxillary incisor after six hours of administration of lipopolysaccharides (LPS). The dental pulp treatment then continued with the administration of eugenol and three different Asiatic acid concentrations (0.5%, 1% and 2%). In the next 72 hours, the teeth were biopsied, and the dental pulp was analysed using the enzyme-linked immunosorbent assay (ELISA) to measure the level of MDA, SOD, TNF-α, beta-endorphins and CGRP. Histopathological examination and the Rat Grimace Scale were utilised to determine the level of inflammation and pain, respectively. Results: The effect of Asiatic Acid on MDA, TNF-α, and CGRP levels decreased significantly compared to the control group (p=<0.001). On the SOD and beta-endorphin levels, Asiatic acid treatment resulted in a considerable rise (p =<0.001). Conclusion: Due to its antioxidant, anti-inflammatory, and antinociceptive characteristics, Asiatic acid can reduce inflammation and pain in acute pulp inflammation due to its ability to decrease MDA, TNFα, and CGRP levels while raising SOD and beta-endorphin levels.

Endogenous Opioid Imbalance as a Potential Factor Involved in the Pathogenesis of Chronic Kidney Disease-Associated Pruritus in Dialysis Patients.

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 ß-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 ß-endorphin concentration in the group of dialysis patients with pruritus compared to the group without pruritus. The ratio of ß-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.

ß-Endorphins are not responsible for delayed gastric emptying of digestible solids after exercise in professional cyclists. A preliminary study.

OBJECTIVE: It has been reported that professional cyclists had an accelerated solid gastric emptying which decreased by increasing the exercise intensity. That could be explained by a predominance of stress-dependent motility inhibitors such gastrointestinal hormones, neurotransmitters and or the predominance of the gastric inhibitory vagal motor circuit. The aim of this preliminary study was to evaluate the role of ß-endorphins, inhibitors of gastric motility, in these findings. METHODS: Gastric emptying of solids marked with Tc99 while resting and plasmatic levels of ß-endorphins were evaluated in 27 healthy controls and 19 professional cyclists (day 1). Besides, gastric emptying of solids was also assessed in cyclists when they reached 50% (day 1) and 75% (day 2) of the maximum oxygen consumption (low and high, respectively), during exercise on the cycle-ergometer. The third day, naloxone was administered in cyclists in order to block the ß-endorphins receptors and gastric emptying was measured when they reached 75% of the maximum oxygen consumption. RESULTS: Basal ß-endorphin levels were lower in cyclists vs controls (p<0.05) and they increased with the exercise intensity (p<0.001). There were no significant differences in gastric emptying of solids with or without naloxone when 75% of the maximum oxygen consumption was reached. CONCLUSIONS: The inhibitory effect of the exercise in the gastric emptying of solids does not seem to be secondary to the action of ß-endorphins, that leaves the gastric inhibitory vagal motor circuit a more likely predominant role.