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International Journal of Molecular... Dec 2020β-Endorphins are peptides that exert a wide variety of effects throughout the body. Produced through the cleavage pro-opiomelanocortin (POMC), β-endorphins are the... (Review)
Review
β-Endorphins are peptides that exert a wide variety of effects throughout the body. Produced through the cleavage pro-opiomelanocortin (POMC), β-endorphins are the primarily agonist of mu opioid receptors, which can be found throughout the body, brain, and cells of the immune system that regulate a diverse set of systems. As an agonist of the body's opioid receptors, β-endorphins are most noted for their potent analgesic effects, but they also have their involvement in reward-centric and homeostasis-restoring behaviors, among other effects. These effects have implicated the peptide in psychiatric and neurodegenerative disorders, making it a research target of interest. This review briefly summarizes the basics of endorphin function, goes over the behaviors and regulatory pathways it governs, and examines the variability of β-endorphin levels observed between normal and disease/disorder affected individuals.
Topics: Animals; Behavior; Behavior, Animal; Brain; Energy Metabolism; Humans; Inflammation; Stress, Physiological; beta-Endorphin
PubMed: 33396962
DOI: 10.3390/ijms22010338 -
Neuroscience Letters Jan 2021We examined the association between endogenous opioid β-endorphin, cancer progression and pain in a transgenic mouse model of breast cancer, with a rat C3(1) simian...
We examined the association between endogenous opioid β-endorphin, cancer progression and pain in a transgenic mouse model of breast cancer, with a rat C3(1) simian virus 40 large tumor antigen fusion gene (C3TAg). C3TAg mice develop ductal epithelial atypia at 8 weeks, progression to intra-epithelial neoplasia at 12 weeks, and invasive carcinoma with palpable tumors at 16 weeks. Consistent with invasive carcinoma at 4 months of age, C3TAg mice demonstrate a significant increase in hyperalgesia compared to younger C3TAg or control FVBN mice without tumors. Our data show that the growing tumor contributes to circulating β-endorphin. As an endogenous ligand of mu opioid receptor, β-endorphin has analgesic activity. Paradoxically, we observed an increase in pain in transgenic breast cancer mice with significantly high circulating and tumor-associated β-endorphin. Increased circulating β-endorphin correlates with increasing tumor burden. β-endorphin induced the activation of mitogenic and survival-promoting signaling pathways, MAPK/ERK 1/2, STAT3 and Akt, observed by us in human MDA-MB-231 cells suggesting a role for β-endorphin in breast cancer progression and associated pain.
Topics: Animals; Biomarkers; Breast Neoplasms; Cancer Pain; Cell Line, Tumor; Disease Progression; Female; Humans; Mice; Mice, Transgenic; beta-Endorphin
PubMed: 33387660
DOI: 10.1016/j.neulet.2020.135601 -
Journal of Affective Disorders Jan 2021Beta-endorphin (BE) has been suggested to play a central role as to why people engage in NSSI. To our knowledge, no study has systematically assessed this potential...
BACKGROUND
Beta-endorphin (BE) has been suggested to play a central role as to why people engage in NSSI. To our knowledge, no study has systematically assessed this potential relationship in adolescents with NSSI.
METHODS
94 adolescents with NSSI (according to DSM-5 criteria) and 35 healthy controls (HC) were enrolled. All participants received heat pain stimulation, with pain threshold and tolerance measured in °C. Plasma BE levels were assessed. Sociodemographic and clinical characteristics were obtained via semi-structured interviews and self-report questionnaires.
RESULTS
Adolescents with NSSI showed increased pain thresholds (t=2.071, p=.040), lower pain intensity (t==2.122, p=.036) and lower plasma BE levels (t==3.182, p=.002) compared to HC. Groups did not differ on pain tolerance (t=0.911, p=.364). Greater pain threshold correlated positively with borderline personality disorder (BPD) symptoms (r=0.182, p=.039), while pain intensity (r=-0.206, p=.033) and BE levels (r=-0.246, p=.007) correlated negatively with depression severity. No significant relationship was found between pain threshold and plasma BE (r=-0.013, p=.882).
LIMITATIONS
Future studies should implement repeated plasma BE measures to assess BE release in association with pain in NSSI. Validity of plasma BE measures compared to central measures should be considered. Assessing the association between pain sensitivity (PS) and BE in a naturalistic setting presents a promising avenue for future research in NSSI.
CONCLUSIONS
Findings support both reduced PS and basal opioid deficiency as independent biological correlates and potential risk-factors for NSSI. Further longitudinal and experimental studies are needed to investigate the role of BE levels and PS as well as their potential association.
Topics: Adolescent; Borderline Personality Disorder; Humans; Pain; Pain Threshold; Plasma; Self-Injurious Behavior; beta-Endorphin
PubMed: 32961416
DOI: 10.1016/j.jad.2020.09.036 -
Anesthesia Progress 1991Beta-endorphin is a peptide with morphine-like effects produced primarily in the anterior lobe of the pituitary gland. After its cleavage from the parent molecule,... (Review)
Review
Beta-endorphin is a peptide with morphine-like effects produced primarily in the anterior lobe of the pituitary gland. After its cleavage from the parent molecule, proopiomelanocortin, beta-endorphin is circulated via the blood stream to interact with specific opioid receptors located throughout the body. The peptide produces analgesia by inhibiting the firing of peripheral somatosensory fibers. It also affects other senses, such as vision, hearing, and smell. Whereas the ability to increase beta-endorphin secretion during times of surgical stress is positively correlated with amelioration of pain, the administration of exogenous opioids, such as fentanyl, reduces plasma beta-endorphin. Decreased beta-endorphin concentrations may play a role in trigeminal neuralgia, migraine headache, and rheumatoid arthritis.
Topics: Humans; Nociceptors; Pain; beta-Endorphin
PubMed: 1814247
DOI: No ID Found -
Archives of Gynecology and Obstetrics Jul 2018To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta...
PURPOSE
To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters.
METHODS
Fifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol.
RESULTS
There was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels.
CONCLUSION
Beta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.
Topics: Adult; Female; Follicular Fluid; Humans; Polycystic Ovary Syndrome; Young Adult; beta-Endorphin
PubMed: 29808249
DOI: 10.1007/s00404-018-4793-6 -
Medical Science Monitor : International... Sep 2020BACKGROUND Increased levels of endogenous opioids have been observed in patients with schizophrenia; however, the influence of these endogenous opioids on the biology of...
BACKGROUND Increased levels of endogenous opioids have been observed in patients with schizophrenia; however, the influence of these endogenous opioids on the biology of schizophrenia remains unclear. The aim of this study was to evaluate the impact of beta-endorphin (BE) on the course of schizophrenia and risk of relapse. MATERIAL AND METHODS The study included 25 patients hospitalized with schizophrenia and 47 controls. Their symptoms were evaluated using Positive and Negative Syndrome Scale (PANSS) and composite index at five points: at the onset of hospitalization; after 4, 6 and 10 weeks of treatment; and after 12 months. ß-endorphin plasma concentrations were assessed in patients at study enrollment and after 6 weeks of treatment. Data regarding rehospitalization during follow-up were also collected. RESULTS Patients had higher BE concentration than controls at study enrollment (P=0.002) and after 6 weeks (P=0.000). BE levels increased during treatment (mean 0.538ng/mL vs. mean 0.624 ng/mL; P=0.007). No correlation was found between BE concentration and PANSS subscale score at any stage of the study. A higher BE level at study enrollment was related to a predominance of negative symptoms after 1 year, measured with composite index (R=-0.404; P=0.045). Patients who were later hospitalized again were significantly more likely to demonstrate an increase in BE levels over 6 weeks (P=0.001). CONCLUSIONS Individuals with schizophrenia demonstrated higher BE concentrations than healthy controls; this tendency was particularly apparent in those affected by negative symptoms. The imbalance in the endogenous opioid system might adversely alter the course of disease and predispose patients to persistence of negative symptoms, despite antipsychotic treatment.
Topics: Adult; Antipsychotic Agents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Schizophrenia; Treatment Outcome; beta-Endorphin
PubMed: 32892205
DOI: 10.12659/MSM.924307 -
Physiological Reports Mar 2021Anorexia nervosa (AN) has a lifetime prevalence of up to 4% and a high mortality rate (~5-10%), yet little is known regarding the etiology of this disease. In an...
Anorexia nervosa (AN) has a lifetime prevalence of up to 4% and a high mortality rate (~5-10%), yet little is known regarding the etiology of this disease. In an attempt to fill the gaps in knowledge, activity-based anorexia (ABA) in rodents has been a widely used model as it mimics several key features of AN including severely restricted food intake and excessive exercise. Using this model, a role for the hypothalamic proopiomelanocortin (POMC) system has been implicated in the development of ABA as Pomc mRNA is elevated in female rats undergoing the ABA paradigm. Since the Pomc gene product α-MSH potently inhibits food intake, it could be that elevated α-MSH might promote ABA. However, the α-MSH receptor antagonist SHU9119 does not protect against the development of ABA. Interestingly, it has also been shown that female mice lacking the mu opioid receptor (MOR), the primary receptor activated by the Pomc-gene-derived opioid β-endorphin, display blunted food anticipatory behavior (FAA), a key feature of ABA. Thus, we hypothesized that the elevation in Pomc mRNA observed during ABA may lead to increased β-endorphin concentrations and MOR activation to promote ABA. Further, given the known sex differences in AN and ABA, we hypothesized that MORs may contribute differentially in male and female mice. Using wild-type and MOR knockout mice of both sexes, a MOR antagonist and careful analysis of food anticipatory behavior and β-endorphin levels, we found 1) increased Pomc mRNA levels in both female and male mice that underwent ABA, 2) increased β-endorphin in female mice that underwent ABA, and 3) blunted FAA in both sexes in response to MOR genetic deletion yet blunted FAA only in males in response to MOR antagonism. The results presented provide support for both hypotheses and suggest that it may be the β-endorphin resulting from increased Pomc transcription that supports the development of some features of ABA.
Topics: Animals; Anorexia; Female; Hypothalamus; Male; Mice; Physical Conditioning, Animal; Pro-Opiomelanocortin; Receptors, Opioid, mu; beta-Endorphin
PubMed: 33661571
DOI: 10.14814/phy2.14788 -
CNS Neuroscience & Therapeutics Oct 2021This study aimed to investigate the regulation of pain hypersensitivity induced by the spinal synaptic transmission mechanisms underlying interleukin (IL)-10 and...
AIM
This study aimed to investigate the regulation of pain hypersensitivity induced by the spinal synaptic transmission mechanisms underlying interleukin (IL)-10 and glucagon-like peptide 1 receptor (GLP-1R) agonist exenatide-induced pain anti-hypersensitivity in neuropathic rats through spinal nerve ligations.
METHODS
Neuropathic pain model was established by spinal nerve ligation of L5/L6 and verified by electrophysiological recording and immunofluorescence staining. Microglial expression of β-endorphin through autocrine IL-10- and exenatide-induced inhibition of glutamatergic transmission were performed by behavioral tests coupled with whole-cell recording of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) through application of endogenous and exogenous IL-10 and β-endorphin.
RESULTS
Intrathecal injections of IL-10, exenatide, and the μ-opioid receptor (MOR) agonists β-endorphin and DAMGO inhibited thermal hyperalgesia and mechanical allodynia in neuropathic rats. Whole-cell recordings of bath application of exenatide, IL-10, and β-endorphin showed similarly suppressed enhanced frequency and amplitude of the mEPSCs in the spinal dorsal horn neurons of laminae II, but did not reduce the frequency and amplitude of mIPSCs in neuropathic rats. The inhibitory effects of IL-10 and exenatide on pain hypersensitive behaviors and spinal synaptic plasticity were totally blocked by pretreatment of IL-10 antibody, β-endorphin antiserum, and MOR antagonist CTAP. In addition, the microglial metabolic inhibitor minocycline blocked the inhibitory effects of IL-10 and exenatide but not β-endorphin on spinal synaptic plasticity.
CONCLUSION
This suggests that spinal microglial expression of β-endorphin mediates IL-10- and exenatide-induced inhibition of glutamatergic transmission and pain hypersensitivity via presynaptic and postsynaptic MORs in spinal dorsal horn.
Topics: Analgesics, Opioid; Animals; Behavior, Animal; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Excitatory Postsynaptic Potentials; Exenatide; Glutamic Acid; Injections, Spinal; Interleukin-10; Microglia; Neuralgia; Neuronal Plasticity; Patch-Clamp Techniques; Rats; Receptors, Opioid, mu; Signal Transduction; Spinal Nerves; Synaptic Transmission; beta-Endorphin
PubMed: 34111331
DOI: 10.1111/cns.13694 -
Molecular Pain 2020This cross-sectional study investigated whether the catechol-O-methyltransferase (COMT) gene acts as a significant regulator of pain signaling pathways, regulates... (Observational Study)
Observational Study
This cross-sectional study investigated whether the catechol-O-methyltransferase (COMT) gene acts as a significant regulator of pain signaling pathways, regulates β-endorphin, and contributes to ethnic differences in pain sensitivity. One-hundred-sixty healthy subjects were enrolled in this study, with Han and Uyghur groups each consisting of 80 participants. Subjects went through six pain threshold experiments. From venous blood, COMT polymorphisms were genotyped, and serum β-endorphin levels were measured. Bivariate correlation analysis and multiple linear regression were used to identify the relationships among genotypes or β-endorphin levels and different types of pain thresholds. Han and Uyghur ethnic differences were determined in terms of acute-pressure pain-perception thresholds, blunt-pressure pain-perception thresholds, blunt-pressure pain-tolerance thresholds, electric pain-tolerance thresholds, β-endorphin levels, and distributions of rs4680 and rs4633 COMT polymorphisms. β-endorphin levels did not correlate with COMT rs4680 or rs4633 genotypes in both Han and Uyghur. Statistical predictors for a lower pain-threshold performance included being young, Uyghur, female, and having a low body mass index, low β-endorphin level, and the rs4680 GA or GG allele. There is the significant difference in pain sensitivity between healthy Han and Uyghur. COMT gene variants and β-endorphin levels contribute to ethnic differences in pain sensitivity.
Topics: Adult; Catechol O-Methyltransferase; China; Cross-Sectional Studies; Ethnicity; Female; Gene Expression Regulation; Genetic Variation; Genotype; Haplotypes; Healthy Volunteers; Humans; Linear Models; Male; Middle Aged; Pain; Pain Measurement; Pain Threshold; Polymorphism, Genetic; Polymorphism, Single Nucleotide; beta-Endorphin
PubMed: 32024434
DOI: 10.1177/1744806920908474 -
Scientific Reports Jul 2023Asthma, a chronic respiratory disease is characterized by airway inflammation, remodelling, airflow limitation and hyperresponsiveness. At present, it is considered as...
Asthma, a chronic respiratory disease is characterized by airway inflammation, remodelling, airflow limitation and hyperresponsiveness. At present, it is considered as an umbrella diagnosis consisting several variable clinical presentations (phenotypes) and distinct pathophysiological mechanisms (endotypes). Recent evidence suggests that oxidative stress participates in airway inflammation and remodelling in chronic asthma. Opioids resembled by group of regulatory peptides have proven to act as an immunomodulator. β-Endorphin a natural and potent endogenous morphine produced in the anterior pituitary gland play role in pain modulation. Therapeutic strategy of many opioids including β-Endorphin as an anti‑inflammatory and antioxidative agent has not been yet explored despite its promising analgesic effects. This is the first study to reveal the role of β-Endorphin in regulating airway inflammation, cellular apoptosis, and oxidative stress via Nrf-2 in an experimental asthmatic model. Asthma was generated in balb/c mice by sensitizing with 1% Toulene Diisocyanate on day 0, 7, 14 and 21 and challenging with 2.5% Toulene Diisocyanate from day 22 to 51 (on every alternate day) through intranasal route. β-Endorphin (5 µg/kg) was administered through the nasal route 1 h prior to sensitization and challenge. The effect of β-Endorphin on pulmonary inflammation and redox status along with parameters of oxidative stress were evaluated. We found that pre-treatment of β-Endorphin significantly reduced inflammatory infiltration in lung tissue and cell counts in bronchoalveolar lavage fluid. Also, pre-treatment of β-Endorphin reduced reactive oxygen species, Myeloperoxidase, Nitric Oxide, Protein and protein carbonylation, Glutathione Reductase, Malondialdehyde, IFN-γ, and TNF-α. Reversely, β-Endorphin significantly increased Superoxide dismutase, Catalase, glutathione, Glutathione-S-Transferase, and activation of NF-E2-related factor 2 (Nrf-2) via Kelch-like ECH-associated protein 1 (Keap1), independent pathway in the lung restoring architectural alveolar and bronchial changes. The present findings reveal the therapeutic potency of β-END in regulating asthma by Keap-1 independent regulation of Nrf-2 activity. The present findings reveal the therapeutic potency of β-Endorphin in regulating asthma.
Topics: Mice; Animals; Analgesics, Opioid; beta-Endorphin; Kelch-Like ECH-Associated Protein 1; Disease Models, Animal; NF-E2-Related Factor 2; Asthma; Oxidative Stress; Inflammation; Bronchoalveolar Lavage Fluid; Glutathione; Apoptosis; Mice, Inbred BALB C
PubMed: 37524754
DOI: 10.1038/s41598-023-38366-5