ABSTRACT
Objectives: This study aimed to determine the effects of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain management in patients undergoing thoracic surgery. Methods: In the prospective, randomized, controlled study, a total of 84 patients undergoing video-assisted thoracoscopic surgery (VATS) were randomly allocated to the TEAS group (Group T) or control group (Group C). Patients in the Group T received TEAS at Neiguan (PC6) and Hegu (LI4) acupoints for 30 min before anesthesia induction and 30 min after thoracoscopic surgery. Patients in the Group C received the same placement of electrodes but without electrical stimulation. The numeric rating scale (NRS) pain score, remifentanil consumption, demand for rescue analgesics and incidence of postoperative nausea and vomiting (PONV), patient satisfaction, and the levels of plasma ß-endorphin (EP) and IL-6 were recorded. Results: Patients in the Group T had significantly lower NRS pain scores at 6 h, 12 h, 24 h, and 48 h after surgery than those in the Group C. Compared with Group C, patients in Group T had lower remifentanil consumption during operation, lower demand for rescue analgesics and lower rate of PONV within 24 h after surgery. Patients in Group T also had lower IL-6 content, higher ß-EP content and higher satisfaction degree than those in the Group C. Conclusions: Perioperative TEAS significantly decreased postoperative pain and rescued analgesia requirements and the incidence of PONV in patients undergoing thoracoscopic surgery, with a higher patient satisfaction. This trial is registered with ChiCTR2100051841.
Subject(s)
Acupuncture Points , Pain, Postoperative , Transcutaneous Electric Nerve Stimulation , Humans , Male , Female , Middle Aged , Pain, Postoperative/prevention & control , Pain, Postoperative/etiology , Transcutaneous Electric Nerve Stimulation/methods , Adult , Aged , Pain Measurement , Prospective Studies , Thoracic Surgery, Video-Assisted/adverse effects , beta-Endorphin/bloodABSTRACT
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.
Subject(s)
Analgesics, Opioid , Receptors, Opioid , Animals , Humans , Analgesics, Opioid/metabolism , beta-Endorphin/metabolism , Dynorphins/metabolism , Enkephalins/metabolism , Opioid Peptides/metabolism , Receptors, Opioid/metabolismABSTRACT
Understanding the relationship between stress and breast cancer development is essential to preventing and alleviating the cancer. Recent research has shed light on the cognitive, physiological, cellular, and molecular underpinnings of how the endorphin pathway and stress pathway affect breast cancer. This chapter consists of two parts. Part 1 will discuss the role of endorphins in breast cancer development. This includes a discussion of three topics: (1) the neurophysiological effect of endorphins on breast tumor growth in vivo, along with further experiments that will deepen our knowledge of how ß-endorphin affects breast cancer; (2) how both the opioid receptor and somatostatin receptor classes alter intracellular signaling in breast cancer cells; and (3) genetic alleles in the opioid signaling pathway that are correlated with increased breast cancer risk. Part 2 will discuss the role of endorphins in recovery from breast cancer. This includes a discussion of three topics: (1) the relationship between breast cancer diagnosis and depression; (2) the effectiveness of cognitive behavioral therapy in reducing stress in breast cancer patients; and (3) the effect of psychotherapy and exercise on preserving telomere length in breast cancer patients.
Subject(s)
Breast Neoplasms , Stress, Psychological , Animals , Female , Humans , beta-Endorphin/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cognitive Behavioral Therapy , Depression/metabolism , Endorphins/metabolism , Receptors, Opioid/metabolism , Signal Transduction , Stress, Psychological/metabolismABSTRACT
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.
Subject(s)
Anxiety , Fear , Pain , Stress, Psychological , Animals , Humans , Anxiety/metabolism , beta-Endorphin/metabolism , Fear/physiology , Opioid Peptides/metabolism , Pain/psychology , Pain/metabolism , Stress, Psychological/metabolismABSTRACT
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.
Subject(s)
beta-Endorphin , Animals , Female , Humans , Pregnancy , beta-Endorphin/metabolism , Endorphins/metabolism , Reproduction/physiology , Sexual Behavior/physiology , Sexuality/physiologyABSTRACT
We determined natural antibodies (n-Abs) to the regulators of the main systems of biochemical homeostasis: ß-endorphin, serotonin, dopamine, histamine, orphanin, angiotensin, GABA, glutamate, bradykinin, vasopressin, thrombin, and α-2-macroglobulin in individuals with phantom pain syndrome (PPS), resulting from amputation after injury. It was established that each patient has an individual immunoprofile, but for all of them there was a significant increase in the level of antibodies to serotonin, histamine, and angiotensin, which reflect the chronicity of the pain syndrome and do not depend on the self-assessment of the severity of PPS. Determination of the role of regulators of biochemical homeostasis in the development of phantom pain showed that, at high, moderate, and weak severity of PPS, the biogenic amine and angiotensinergic systems are activated. A decrease in PPS intensity normalizes deviations in all immunological parameters. The levels of n-Abs for the pain (ß-endorphin) and analgesic (orphanin) systems are significant only at low PPS. Monitoring the individual profile of n-Abs to endogenous regulators allows us to obtain an objective picture of the pain status of the patient's body.
Subject(s)
Phantom Limb , Humans , Phantom Limb/physiopathology , Phantom Limb/immunology , Male , Female , beta-Endorphin , Middle Aged , Antibodies/immunology , Adult , Histamine/immunology , Histamine/metabolism , Angiotensins/immunology , Serotonin/metabolism , Serotonin/immunologyABSTRACT
OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), ß-endorphin (ß-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, ß-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and ß-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and ß-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The ß-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the ß-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001). CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of ß-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.
Subject(s)
Drugs, Chinese Herbal , Serotonin , Humans , Drugs, Chinese Herbal/administration & dosage , Female , Middle Aged , Adult , Male , Serotonin/blood , Aged , Young Adult , Vasoactive Intestinal Peptide/blood , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/blood , beta-Endorphin/blood , Adolescent , Hemostatics/administration & dosage , Hemostasis/drug effectsABSTRACT
It has been widely recognized that electroacupuncture (EA) inducing the release of ß-endorphin represents a crucial mechanism of EA analgesia. The arcuate nucleus (ARC) in the hypothalamus is a vital component of the endogenous opioid peptide system. Serving as an integration center, the periaqueductal gray (PAG) receives neural fiber projections from the frontal cortex, insular cortex, and ARC. However, the specific mechanisms how EA facilitates the release of ß-endorphin within the ARC, eliciting analgesic effects are yet to be elucidated. In this study, we conducted in vivo and in vitro experiments by transcriptomics, microdialysis, photogenetics, chemical genetics, and calcium imaging, combined with transgenic animals. Firstly, we detected 2 Hz EA at the Zusanli (ST36) increased the level of ß-endorphin and transcriptional level of proopiomelanocortin (POMC). Our transcriptomics profiling demonstrated that 2 Hz EA at the ST36 modulates the expression of c-Fos and Jun B in ARC brain nuclear cluster, and the transcriptional regulation of 2 Hz EA mainly occur in POMC neurons by Immunofluorescence staining verification. Meaning while, 2 Hz EA specifically activated the cAMP-PKA-CREB signaling pathway in ARC which mediating the c-Fos and Jun B transcription, and 2 Hz EA analgesia is dependent on the activation of cAMP-PKA-CREB signaling pathway in ARC. In order to investigate how the ß-endorphin produced in ARC transfer to integration center PAG, transneuronal tracing technology was used to observe the 2 Hz EA promoted the neural projection from ARC to PAG compared to 100 Hz EA and sham mice. Inhibited PAGGABA neurons, the transfer of ß-endorphin from the ARC nucleus to the PAG nucleus through the ARCPOMC-PAGGABA neural circuit. Furthermore, by manipulating the excitability of POMC neurons from ARCPOMC to PAGGABA using inhibitory chemogenetics and optogenetics, we found that this inhibition significantly reduced transfer of ß-endorphin from the ARC nucleus to the PAG nucleus and the effectiveness of 2 Hz EA analgesia in neurological POMC cyclization recombination enzyme (Cre) mice and C57BL/6J mice, which indicates that the transfer of ß-endorphin depends on the activation of POMC neurons prefect from ARCPOMC to PAGGABA. These findings contribute to our understanding of the neural circuitry underlying the EA pain-relieving effects and maybe provide valuable insights for optimizing EA stimulation parameters in clinical pain treatment using the in vivo dynamic visual investigating the central analgesic mechanism.
Subject(s)
Arcuate Nucleus of Hypothalamus , Electroacupuncture , Periaqueductal Gray , Pro-Opiomelanocortin , beta-Endorphin , Animals , Pro-Opiomelanocortin/metabolism , Pro-Opiomelanocortin/genetics , Periaqueductal Gray/metabolism , Arcuate Nucleus of Hypothalamus/metabolism , Electroacupuncture/methods , beta-Endorphin/metabolism , Male , Mice, Transgenic , Mice, Inbred C57BL , Mice , Proto-Oncogene Proteins c-fos/metabolism , Neurons/metabolismABSTRACT
BACKGROUND: In recent years, the incidence of menopause insomnia has gradually increased, seriously affecting women's physical and mental health. METHODS: Total 82 climacteric insomnia patients received from January 2021 to January 2023 were divided into 2 groups at random. In control group, 41 cases received conventional Western medicine, and in study group, 41 cases received acupuncture combined with Ningshen mixture. Clinical effectiveness of both groups was compared, neurotransmitter levels, TCM syndrome integral and Pittsburgh Sleep Quality Index (PSQI) were assessed in both groups. Meanwhile, the recurrence rate and safety were evaluated in 2 groups. RESULTS: The curative effect in study group was better than that in control group (Pâ <â .05). After treatment, the expressions of 5-hydroxytryptamine and ß-endorphin (ß-EP) in study group were higher than control group (Pâ <â .05); TCM syndrome scores and PSQI scores in study group were lower than control group (Pâ <â .05). The total recurrence rate in study group was obviously lower than control group at 3 months after treatment (Pâ <â .05). There were no serious adverse reactions in both group, and no distinct difference between 2 groups was found (Pâ >â .05). CONCLUSION: Acupuncture united with Ningshen mixture has a significant therapeutic effect and high safety in climacteric insomnia patients. It can effectively improve the neurotransmitter levels, clinical symptoms and sleep quality, and reduce the recurrence rate of climacteric insomnia patients, which has high clinical application value and is worthy of clinical promotion.
Subject(s)
Acupuncture Therapy , Drugs, Chinese Herbal , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/therapy , Female , Acupuncture Therapy/methods , Middle Aged , Drugs, Chinese Herbal/therapeutic use , Combined Modality Therapy , Menopause , Treatment Outcome , Sleep Quality , beta-Endorphin/blood , beta-Endorphin/metabolism , Serotonin/metabolismABSTRACT
Hay evidencia parcial de que los niveles elevados de la β-endorfina sanguínea se asocian a la adicción suicida en los adultos, pero apenas hay datos sobre los adolescentes. La β-endorfina sanguínea, con un importante papel en los mecanismos de gestión de las adicciones, puede inducir euforia y felicidad, recompensar y reforzar el comportamiento suicida. Para probar si los grandes repetidores de intentos de suicidio (5 o más intentos de suicidio) y de conductas autolesivas (20 o más episodios de autolesiones) tienen unos niveles de biomarcadores más elevados, se selecciona una muestra de 43 pacientes de entre 12 y 17 años que acuden al Servicio de Urgencias Psiquiátricas en el Hospital Universitario Puerta de Hierro Majadahonda. Diez presentan 5 o más intentos de suicidio, 35 presentan 20 o más episodios autolesivos y 10 presentan ambas características, y la mayoría de los adolescentes cumplían criterios de adicción para autolesiones y suicidio. Los resultados sugieren que todos los pacientes que presentaban adicción al suicidio también presentaban adicción a la autolesión. Los niveles de ACTH, cortisol y β-endorfina sanguíneos y de cortisol en orina fueron muy elevados, pero no diferenciaban a los grandes repetidores del resto de adolescentes. (AU)
There is partial evidence that elevated levels of blood β-endorphin are associated with suicidal addiction in adults, but hardly any data on adolescents. Blood β-endorphin, with an important role in addiction management mechanisms, can induce euphoria and happiness, reward and reinforce suicidal behavior. To test whether high repeaters of suicide attempts (5 or more suicide attempts) and self-injurious behaviors (20 or more episodes of self-injury) have higher biomarker levels, a sample of 43 patients aged 12-17 years attending the Psychiatric Emergency Department at the Hospital Universitario Puerta de Hierro Majadahonda is recruited. Ten present 5 or more suicide attempts, 35 present 20 or more self-injurious episodes and 10 present both characteristics, and most of the adolescents meet addiction criteria for self-injury and suicide. The results suggest that all patients with addiction to suicide also had addiction to self-injury. Blood ACTH, cortisol and β-endorphin and urine cortisol levels were very elevated, but did not differentiate heavy repeaters from the rest of the adolescents. (AU)
Subject(s)
Humans , Male , Female , Adolescent , Biomarkers/blood , Biomarkers/urine , Self-Injurious Behavior , Suicide, Attempted , Suicidal Ideation , beta-EndorphinABSTRACT
Mutations that perturb leptin-melanocortin signaling are known to cause hyperphagia and obesity, but energy expenditure has not been well studied outside rodents. We report on a common canine mutation in pro-opiomelanocortin (POMC), which prevents production of ß-melanocyte-stimulating hormone (ß-MSH) and ß-endorphin but not α-MSH; humans, similar to dogs, produce α-MSH and ß-MSH from the POMC propeptide, but rodents produce only α-MSH. We show that energy expenditure is markedly lower in affected dogs, which also have increased motivational salience in response to a food cue, indicating increased wanting or hunger. There was no difference in satiety at a modified ad libitum meal or in their hedonic response to food, nor disruption of adrenocorticotropic hormone (ACTH) or thyroid axes. In vitro, we show that ß-MSH signals comparably to α-MSH at melanocortin receptors. These data implicate ß-MSH and ß-endorphin as important in determining hunger and moderating energy expenditure and suggest that this role is independent of the presence of α-MSH.
Subject(s)
beta-Endorphin , beta-MSH , Humans , Dogs , Animals , beta-Endorphin/genetics , Basal Metabolism , Pro-Opiomelanocortin/genetics , Hunger , alpha-MSH/geneticsABSTRACT
ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of ß-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.
Subject(s)
Analgesia , Naloxone , Transcranial Magnetic Stimulation , Humans , Transcranial Magnetic Stimulation/methods , Male , Female , Adult , Double-Blind Method , Analgesia/methods , Young Adult , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Dorsolateral Prefrontal Cortex/physiology , Motor Cortex/physiology , Motor Cortex/drug effects , Pain Management/methods , Pain Measurement/methods , beta-Endorphin/blood , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiology , Prefrontal Cortex/metabolismABSTRACT
OBJECTIVE: Based upon similarities between the urge to move and sensory discomfort of restless legs syndrome (RLS) and properties of melanocortin hormones, including their incitement of movement and hyperalgesia, we assessed plasma and cerebrospinal fluid (CSF) α-melanocyte-stimulating hormone (α-MSH) and ß-endorphin in RLS patients and controls. METHODS: Forty-two untreated moderate-to-severe RLS patients and 44 matched controls underwent venipuncture at 19:00, 20:30, and 22:00; 37 RLS and 36 controls had lumbar puncture at 21:30. CSF and plasma were analyzed for pro-opiomelanocortin (POMC), adrenocorticotropin hormone (ACTH), α-MSH, ß-MSH, and ß-endorphin by immunoassay. RLS severity was assessed by International RLS Study Group Severity Scale. RESULTS: RLS participants were 52.7 ± 12.0 years old, 61.9% were women, 21.4% had painful RLS, and RLS severity was 24.8 ± 9.0. Controls had similar age and sex. Plasma ACTH, α-MSH, and ß-endorphin were similar between groups. Plasma POMC was significantly greater in RLS than controls (17.0 ± 11.5 vs 12.7 ± 6.1fmol/ml, p = 0.048). CSF ACTH was similar between groups. CSF ß-MSH was significantly higher in painful than nonpainful RLS or controls (48.2 ± 24.8 vs 32.1 ± 14.8 vs 32.6 ± 15.2pg/ml, analysis of variance [ANOVA] p = 0.03). CSF α-MSH was higher in RLS than controls (34.2 ± 40.9 vs 20.3 ± 11.0pg/ml, p = 0.062). CSF ß-EDP was lowest in painful RLS, intermediate in nonpainful RLS, and highest in controls (8.0 ± 3.4 vs 10.8 ± 3.1 vs 12.3 ± 5.0pg/ml, ANOVA p = 0.049). The ratio of the sum of CSF α- and ß-MSH to CSF ß-endorphin was highest, intermediate, and lowest in painful RLS, nonpainful RLS, and controls (p = 0.007). INTERPRETATION: CSF ß-MSH is increased and CSF ß-endorphin decreased in RLS patients with painful symptoms. ANN NEUROL 2024;95:688-699.
Subject(s)
Endorphins , Neuropeptides , Restless Legs Syndrome , Humans , Female , Adult , Middle Aged , Male , Pro-Opiomelanocortin/analysis , alpha-MSH/analysis , beta-Endorphin/analysis , Melanocortins , beta-MSH , Adrenocorticotropic HormoneABSTRACT
Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions of ketamine and their molecular correlates in the medial prefrontal cortex (mPFC) are blocked by acute systemic administration of naltrexone, a competitive opioid receptor antagonist. Naltrexone delivered directly into the mPFC similarly disrupts the behavioral effects of ketamine. Ketamine treatment rapidly increases levels of ß-endorphin and the expression of the µ-opioid receptor gene (Oprm1) in the mPFC, and the expression of gene that encodes proopiomelanocortin, the precursor of ß-endorphin, in the hypothalamus, in vivo. Finally, neutralization of ß-endorphin in the mPFC using a specific antibody prior to ketamine treatment abolishes both behavioral and molecular effects. Together, these findings indicate that presence of ß-endorphin and activation of opioid receptors in the mPFC are required for the antidepressant-like actions of ketamine.
Subject(s)
Ketamine , Rats , Animals , Analgesics, Opioid/pharmacology , beta-Endorphin/metabolism , beta-Endorphin/pharmacology , Naltrexone/pharmacology , Naltrexone/metabolism , Antidepressive Agents , Prefrontal Cortex/metabolismABSTRACT
Although the involvement of ß-endorphin (ß-ERP) in vertebrate reproduction has been suggested, its role in testicular activity is not clear in fish. We describe the influence of ß-ERP on spermatogenesis in a cichlid fish in the present paper. In comparison to the control group, the administration of ß-ERP (3 µg) caused a significant increase in the number of spermatogonia-A and spermatids. Following treatment with ß-ERP (6 µg), a significant increase in the number of spermatogonia-A was observed, whereas the numbers of all the other germ cells, excluding spermatogonia-B, significantly decreased in comparison to those in the control group. In addition, treatment of fish with 6 µg ß-ERP resulted in a significant reduction in the dimensions of the lumen and seminiferous lobules, the level of immunopositive androgen receptor (AR) expression in Sertoli cells, and the percentage of luteinizing hormone (LH) immunolabeled in the pituitary compared to those in the control group or the group treated with 3 µg ß-ERP. In contrast, the intensity of AR immunoreactivity and the percentage of LH immunolabeling were substantially increased in fish treated with 3 µg ß-ERP compared to those in the control group. These findings reveal for the first time that a low dose of ß-ERP stimulates the recruitment of spermatogonia as well as spermateleosis, whereas a high concentration affects the recruitment of germ cells prior to meiotic division in tilapia. These results suggest that ß-ERP exerts modulatory effects at the testicular and hypophysial levels through alterations in AR expression and LH secretory activity, respectively, in teleosts.
Subject(s)
Testis , Tilapia , Male , Animals , Testis/metabolism , Tilapia/metabolism , beta-Endorphin/metabolism , beta-Endorphin/pharmacology , Opioid Peptides/metabolism , Opioid Peptides/pharmacology , Spermatogenesis , Luteinizing Hormone/metabolism , SpermatogoniaABSTRACT
Beta-endorphin (ß-E) is an opioid peptide linked to the behavioral effects of ethanol. For example, ß-E provides negative feedback to inhibit the hypothalamic-pituitary-adrenal (HPA) stress axis, and neuroadaptation of this system to ethanol may facilitate sex differences in disordered drinking. Locomotor sensitivity to ethanol may also influence the risk for addiction; however, the role of ß-E in psychomotor effects of ethanol is not fully understood. We examined the role of ß-E and sex on locomotor effects of ethanol using adult male and female wild-type C57BL/6J and ß-E deficient B6.129S2-Pomctm1Low/J mice in a parallel rod floor apparatus following 0.75 or 2.0 g/kg ethanol. Beginning 15 min after intraperitoneal injection, we recorded foot slips, distance traveled, slips per meter, first instance of immobility, and total time spent off-balance (lying on the floor) over 15 min, and collected blood for analysis of ethanol concentration 60 min after injection. Overall, ß-E deficient mice were more sedated and ataxic following ethanol; at the lower dose they slipped more frequently and had a higher rate of slips per meter traveled. At the higher dose, ß-E deficient mice were predominantly sedated, slipping less frequently, and traveling less, as well as spending more time off-balance and becoming immobile sooner. Genotype interacted with sex in that male ß-E deficient mice slipped more frequently than their female counterparts, suggesting that ß-E may elicit sex-dependent effects of ethanol-induced ataxia. Blood ethanol concentration did not differ between any group, suggesting that behavioral differences result from altered sensitivity to ethanol. Our data support the contention that ß-E modulates the locomotor effects of ethanol and may influence ataxia in a sex-dependent manner. These findings help elucidate the role of ß-E in diverging behavioral responses to ethanol and may aid the development of targeted treatments for alcohol use disorders.
Subject(s)
Alcoholism , Hypnotics and Sedatives , Female , Mice , Male , Animals , Hypnotics and Sedatives/pharmacology , beta-Endorphin , Alcoholism/genetics , Mice, Inbred C57BL , Ethanol , Ataxia/chemically inducedABSTRACT
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, ß-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 ß-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.
Subject(s)
Analgesics, Opioid , Restless Legs Syndrome , Humans , Rats , Mice , Animals , Analgesics, Opioid/pharmacology , Analgesics, Opioid/therapeutic use , Restless Legs Syndrome/diagnosis , Restless Legs Syndrome/drug therapy , Melanocortins/therapeutic use , beta-Endorphin/therapeutic use , Iron , DopamineABSTRACT
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 ß-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 ß-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100ß, 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, S100ß 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 .
Subject(s)
Aneurysm , Transcutaneous Electric Nerve Stimulation , Humans , Remifentanil , Analgesics, Opioid , Acupuncture Points , Prospective Studies , beta-Endorphin , Craniotomy , Superoxide DismutaseABSTRACT
Solar ultraviolet B (UVB) radiation triggers excessive inflammation, disrupting the epidermal barrier, and can eventually cause skin cancer. A previous study reported that under UVB irradiation, epidermal keratinocytes synthesize the proopiomelanocortin-derived peptide ß-endorphin, which is known for its analgesic effect. However, little is known about the role of ß-endorphin in UVB-exposed skin. Therefore, in this study, we aimed to explore the protective role of ß-endorphin against UVB irradiation-induced damage to the skin barrier in normal human keratinocytes (NHKs) and on a human skin equivalent model. Treatment with ß-endorphin reduced inflammatory responses in UVB-irradiated NHKs by inactivating the NF-κB signaling pathway. Additionally, we found that ß-endorphin treatment reversed UVB-induced abnormal epidermal proliferation and differentiation in NHKs and, thus, repaired the skin barrier in UVB-treated skin equivalents. The observed effects of ß-endorphin on UVB-irradiated NHKs were mediated via blockade of the Akt/mTOR signaling pathway. These results reveal that ß-endorphin might be useful against UVB-induced skin injury, including the disruption of the skin barrier function.
Subject(s)
Epidermis , beta-Endorphin , Humans , beta-Endorphin/metabolism , Epidermis/metabolism , Keratinocytes/metabolism , Signal Transduction , Inflammation/prevention & control , Inflammation/metabolism , Ultraviolet Rays/adverse effects , Mechanistic Target of Rapamycin Complex 1/metabolismABSTRACT
OBJECTIVES: To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (ß-EP) level in puerpera. METHODS: Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum ß-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups. RESULTS: At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), ß-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the ß-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05). CONCLUSIONS: Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum ß-EP level and the increase of pain threshold so that analgesia is obtained.