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Biomedicines Jul 2023Caring for patients with Crohn's disease (CD) is a serious challenge in modern medicine. The increasing incidence of CD among adolescents and the severe course of the...
Caring for patients with Crohn's disease (CD) is a serious challenge in modern medicine. The increasing incidence of CD among adolescents and the severe course of the disease create the need for new methods of diagnosis and therapy. Endogenous opioids are a group of low molecular weight chemical compounds with analgesic and anti-inflammatory properties. Endorphins, enkephalins, and dynorphins may have potentially beneficial effects on the course of CD. Previous research data on this topic are inconsistent. Some authors have reported an increase in the concentration of leukocytes during the course of inflammatory bowel disease (IBD) while others have described a downward trend, explained by DPP-IV enzyme activity. Even fewer data are available on plasma endo-opioid level. There is also a lack of comprehensive studies that have assessed the endo-opioid system in patients with IBD. Therefore, the objective of this study was to measure the serum concentrations of human β-endorphin, human proenkephalin (A), and human big dynorphin in CD patients in the acute phase of the disease, during hospital treatment, and in the remission state. All determinations were performed using ELISA kits. The results of our study showed that the concentrations of all the tested endo-opioids, especially β-endorphin and proenkephalin (A), were reduced in adolescents with CD compared to those in the healthy control group, during the acute phase of the disease, and in the remission state. Modulation of the endogenous opioid system and the use of selective nonnarcotic agonists of opioid receptors seems to be promising goals in the future treatment of CD.
PubMed: 37509676
DOI: 10.3390/biomedicines11072037 -
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 -
Pain Sep 2023The efficacy of acupuncture in treating pain diseases has been recognized in clinical practice, and its mechanism of action has been a hot topic in academic acupuncture...
The efficacy of acupuncture in treating pain diseases has been recognized in clinical practice, and its mechanism of action has been a hot topic in academic acupuncture research. Previous basic research on acupuncture analgesia has focused mostly on the nervous system, with few studies addressing the immune system as a potential pathway of acupuncture analgesia. In this study, we investigated the effect of electroacupuncture (EA) on the β-endorphins (β-END) content, END-containing leukocyte type and number, sympathetic neurotransmitter norepinephrine (NE), and chemokine gene expression in inflamed tissues. To induce inflammatory pain, about 200 µL of complete Frester adjuvant (CFA) was injected into the unilateral medial femoral muscle of adult Wistar rats. Electroacupuncture treatment was performed for 3 days beginning on day 4 after CFA injection, with parameters of 2/100 Hz, 2 mA, and 30 minutes per treatment. The weight-bearing experiment and enzyme-linked immunosorbent assay showed that EA treatment significantly relieved spontaneous pain-like behaviors and increased the level of β-END in inflamed tissue. Injection of anti-END antibody in inflamed tissue blocked this analgesic effect. Flow cytometry and immunofluorescence staining revealed that the EA-induced increase in β-END was derived from opioid-containing ICAM-1 + /CD11b + immune cells in inflamed tissue. In addition, EA treatment increased the NE content and expression of β2 adrenergic receptor (ADR-β2) in inflammatory tissues and upregulated Cxcl1 and Cxcl6 gene expression levels. These findings provide new evidence for the peripheral analgesic effect of acupuncture treatment by recruiting β-END-containing ICAM-1 + /CD11b + immune cells and increasing the β-END content at the site of inflammation.
Topics: Rats; Animals; beta-Endorphin; Intercellular Adhesion Molecule-1; Electroacupuncture; Neutrophils; Rats, Wistar; Pain; Analgesics; Acupuncture Analgesia
PubMed: 37027145
DOI: 10.1097/j.pain.0000000000002892 -
Nature Communications Nov 2023Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying...
Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of β-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.
Topics: Animals; Humans; Rats; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Epigenesis, Genetic; MicroRNAs; Neuralgia; Neurons; Rodentia
PubMed: 37945654
DOI: 10.1038/s41467-023-43022-7 -
Scientific Reports Dec 2023Solar ultraviolet B (UVB) radiation triggers excessive inflammation, disrupting the epidermal barrier, and can eventually cause skin cancer. A previous study reported...
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 β-endorphin, which is known for its analgesic effect. However, little is known about the role of β-endorphin in UVB-exposed skin. Therefore, in this study, we aimed to explore the protective role of β-endorphin against UVB irradiation-induced damage to the skin barrier in normal human keratinocytes (NHKs) and on a human skin equivalent model. Treatment with β-endorphin reduced inflammatory responses in UVB-irradiated NHKs by inactivating the NF-κB signaling pathway. Additionally, we found that β-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 β-endorphin on UVB-irradiated NHKs were mediated via blockade of the Akt/mTOR signaling pathway. These results reveal that β-endorphin might be useful against UVB-induced skin injury, including the disruption of the skin barrier function.
Topics: Humans; beta-Endorphin; Epidermis; Keratinocytes; Signal Transduction; Inflammation; Ultraviolet Rays; Mechanistic Target of Rapamycin Complex 1
PubMed: 38102220
DOI: 10.1038/s41598-023-49886-5 -
Cureus Aug 2023Overall, there is a great need within sports medicine to ensure that athletes can return from injury in an efficient, yet thorough manner. It is crucial to not avoid... (Review)
Review
Overall, there is a great need within sports medicine to ensure that athletes can return from injury in an efficient, yet thorough manner. It is crucial to not avoid necessary difficulties in this process but also to ensure time-efficient rehabilitation. One of the more promising techniques to achieve timely recovery is blood flow restriction (BFR) training. BFR training is a growing and novel development that could be a vital tool to lighten the burden of recovery from injury in athletes. BFR utilizes a pneumatic tourniquet to limit blood flow in specific areas of the body. The use of BFR has been shown to potentially enhance the analgesic effects of exercise-induced hypoalgesia (EIH). By limiting pain, athletes will be less burdened by mobility and loading exercises required for them to effectively return to play. In a field where time away from sports can have massive implications, the need for tools to assist in the acceleration of the rehabilitation process is vital. Much of the work that has already been done in the field has been able to exploit the benefits of EIH and further enhance the body's capabilities through BFR. Studies have compared EIH at low- and high-intensity settings utilizing BFR with both resistance and aerobic exercise. The results of these studies show comparable beta-endorphin levels with high-intensity exercise without BFR and low-intensity exercise with BFR. Low-intensity training with BFR had greater local pain relief, perhaps indicating the promising effects of BFR in enhancing EIH. By reviewing the current literature on this topic, we hope that further progress can be made to better understand the mechanism behind BFR and its ability to enhance EIH. Currently, local metabolites are a major focus for the potential mechanism behind these effects. Mas-related G-protein-coupled receptors (Mrgprs) contribute to local pain pathways via mast cell degranulation. Similarly, chemokine receptor 2/chemokine ligand 2 (CCR2/CCL2) triggers mast cell degranulation and inflammation-induced pain. Finally, pain-reducing effects have been linked to anti-inflammatory IL-10 signaling and anaerobic metabolites via transient receptor potential vanilloid 1 (TRPV1). Through a better understanding of these metabolites and their mechanisms, it is possible to further exploit the use of BFR to not only serve athletes recovering from injury but also apply this information to better serve all patients.
PubMed: 37692724
DOI: 10.7759/cureus.43219 -
Translational Psychiatry Feb 2024Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a...
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 β-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 β-endorphin, in the hypothalamus, in vivo. Finally, neutralization of β-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 β-endorphin and activation of opioid receptors in the mPFC are required for the antidepressant-like actions of ketamine.
Topics: Rats; Animals; Ketamine; Analgesics, Opioid; beta-Endorphin; Naltrexone; Antidepressive Agents; Prefrontal Cortex
PubMed: 38346984
DOI: 10.1038/s41398-024-02796-0 -
Frontiers in Physiology 2023The present review considers the putative hormonal opioid peptides in birds. In birds and all other vertebrates, there are four opioid related genes encoding a series of... (Review)
Review
The present review considers the putative hormonal opioid peptides in birds. In birds and all other vertebrates, there are four opioid related genes encoding a series of peptides. These genes are, respectively, proenkephalin (PENK), prodynorphin (PDYN), pronociceptin (PNOC) and proopiomelanocortin (POMC). Proenkephalin (PENK) encodes Met- and Leu-enkephalin together with peptides containing met enkephalin motifs in birds, mammals and reptiles. Proopiomelanocortin (POMC) encodes β endorphin together with adrenocorticotropic hormone (ACTH), and melanocyte stimulating hormone (MSH). Prodynorphin (PDYN) encoding dynorphins A and B with α- and β-neoendorphins together intermediate polypeptides across the vertebrates. Pronociceptin (PNOC) encodes nociceptin together with possibly putative avian nocistatin and a non-opioid peptide derived from the C terminal of pronociceptin. There is a high degree of identity in the sequences of enkephalin peptides, dynorphin-A and B and nociceptin in birds and, to a less extent, across vertebrates. The opioid peptides exert effects related to pain together with other biological actions such as growth/development acting via a series of opioid receptors. What is unclear, particularly in birds, is the biological roles and interactions (additivity, antagonistic and synergistic) for the individual opioid peptides, the processing of the prohormones in different tissues and the physiological relevance of the different peptides and, particularly, of the circulating forms.
PubMed: 37346481
DOI: 10.3389/fphys.2023.1164031 -
American Journal of Translational... 2023To analyze the effect and safety of ultrasound-guided continuous stellate ganglion blockade (CSGB) on neurovascular headache.
OBJECTIVE
To analyze the effect and safety of ultrasound-guided continuous stellate ganglion blockade (CSGB) on neurovascular headache.
METHODS
The clinical data of 137 patients with neurovascular headache treated in the First Affiliated Hospital of Hebei North University from March 2019 to October 2021 were analyzed retrospectively. According to the treatment schemes, the patients were assigned to the control group (69 cases, treated with flunarizine combined with Oryzanol tablets), or the observation group (68 cases, treated with ultrasound-guided CSGB on the basis of the treatment to the control group). The efficacy, headache symptoms, negative emotions, cerebral artery blood flow velocity, vasoactive substance levels and adverse reactions of the two groups were compared. Univariate and logistic multivariate analyses were conducted to explore the risk factors for recurrence of neurovascular headache after treatment.
RESULTS
The observation group showed a notably higher total effective rate than the control group (95.59% 84.06%, <0.05). In contrast to the control group, the observation group had notably lower self-rating depression scale (SDS) and Self-Rating Anxiety Scale (SAS) scores and showed notably lower posterior cerebral artery (PCA), middle cerebral artery (MCA), basilar artery (BA) and anterior cerebral artery (ACA) levels (P<0.05). After the treatment, the observation group showed higher levels of serum 5-hydroxy tryptamine (5-HT) and Beta-Endorphin (β-EP) than the control group, but a lower serum neurotensin (NT) level than the control group. Moreover, the incidence of adverse reactions in the two groups was not greatly different (10.29% 5.80%). The observation group showed a lower recurrence rate within 6 months after treatment than the control group (5.88% 18.84%, P<0.05). Univariate and logistic multivariate analyses showed that occupation (physical labor), smoking history and sleep quality (poor) may be the risk factors for recurrence of neurovascular headache after treatment (>1, <0.05), while CSGB may be the protective factor (OR<1, P<0.05).
CONCLUSION
Ultrasound-guided CSGB has obvious analgesic effect on patients with neurovascular headache, which can shorten the duration of headache, improve the cerebral artery blood flow velocity, regulate the levels of vasoactive substances, relieve negative emotions, and lower the recurrence rate, with a high safety.
PubMed: 37434854
DOI: No ID Found -
Tobacco Use Insights 2023This study examined a supervised moderate-intensity aerobic exercise programme's effectiveness in regulating the Tobacco Withdrawal Symptoms (TWS) during temporary...
This study examined a supervised moderate-intensity aerobic exercise programme's effectiveness in regulating the Tobacco Withdrawal Symptoms (TWS) during temporary abstinence. This was a single group, pre and post-quasi intervention study. Thirty daily smokers participated in an 8-week supervised moderate-intensity aerobic exercise programme. We assessed the TWS, smoking urge, mood and stress-pleasure related hormonal variables after the aerobic exercise intervention. The measurements were conducted after overnight abstinence at baseline, post-intervention (at week-8) and post-detraining (at week-10). TWS components, smoking urge and mood were found to improve. For hormonal variables, cortisol and beta-endorphin except adrenaline showed insignificant changes at post-intervention and de-training. The findings suggest moderate-intensity exercise might help in reducing withdrawal symptoms and its adverse effects. Thus, exercise is an effective adjunct treatment in a smoking cessation programme.
PubMed: 37255578
DOI: 10.1177/1179173X231179811