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Brain and Behavior Apr 2017Cerebral malaria (CM) is the most lethal form of malaria, yet its pathogenesis is not fully understood. Cytoadherence, sequestration, alterations in cytokine expression,...
OBJECTIVES
Cerebral malaria (CM) is the most lethal form of malaria, yet its pathogenesis is not fully understood. Cytoadherence, sequestration, alterations in cytokine expression, inflammation, and microvascular obstruction are all hypothesized to be important in the aetio-pathogenesis of coma which characterizes cerebral malaria and the death which sometimes result. Beta (β)-endorphin has been postulated to be involved in the pathogenetic processes of inflammation and cytokine expression, although the exact role is unknown. The aim of this study was to determine the levels of β-endorphin in cerebrospinal fluid (CSF) and plasma of children with CM and compare the levels of β-endorphin in the plasma of children with CM with that of apparently healthy age- and sex-matched controls at Ile-Ife, Nigeria.
MATERIALS AND METHODS
Additional to the standard investigation for CM, CSF and venous blood samples were obtained from the subjects for the determination of β-endorphin levels.
RESULTS
Forty children with CM were studied along with forty age- and sex-matched controls. The mean CSF β-endorphin (± SD) level for the children with CM was 1.8 ± 0.9 pmol/L. The mean plasma β-endorphin levels at admission (3.1 ± 2.0 pmol/L) and discharge (4.1 ± 3.3 pmol/L) were higher in children with CM than in the control subjects (2.7 ± 0.7 pmol/L). However, only the mean plasma β-endorphin levels at discharge was significantly higher than that of controls (=.012).
CONCLUSION
Children with CM had higher mean plasma β-endorphin levels compared to the controls and there was increased production of β-endorphins in children with CM during the course of the illness.
Topics: Aging; Biomarkers; Blood Chemical Analysis; Body Temperature; Child; Child Development; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Malaria, Cerebral; Male; Sex Characteristics; Treatment Outcome; beta-Endorphin
PubMed: 28413714
DOI: 10.1002/brb3.673 -
PloS One Aug 2009Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and...
BACKGROUND
Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma beta-endorphin levels and their relationship in a large group of individuals with autism.
METHODOLOGY/PRINCIPAL FINDINGS
The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma beta-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Delta heart rate) was significantly greater than for controls (mean+/-SEM; 6.4+/-2.5 vs. 1.3+/-0.8 beats/min, P<0.05). Plasma beta-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity.
CONCLUSIONS/SIGNIFICANCE
The greater heart rate response to venepuncture and the elevated plasma beta-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain.
Topics: Adolescent; Autistic Disorder; Case-Control Studies; Child; Female; Humans; Male; Pain; beta-Endorphin
PubMed: 19707566
DOI: 10.1371/journal.pone.0005289 -
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 -
Endocrinology Sep 2012Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and...
Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake. In this study we examined the effects of intracerebroventricular (icv) β-EP on food intake and its ability to antagonize the negative effects of α-MSH on energy balance in male rats. A single icv injection of β-EP stimulated food intake over a 2- to 6-h period during both the light and dark cycles. This effect was, however, not sustained with chronic icv β-EP infusion. In the next study, a subthreshold dose of β-EP was injected together with Nle(4), d-Phe(7) (NDP)-MSH after a 16-h fast, and the negative effects of NDP-MSH on refeeding and body weight gain were partially reversed. Finally, peptide interactions were studied in a chronic icv infusion model. Weight gain and food intake were significantly suppressed in the NDP-MSH group during the entire study. A subthreshold dose of β-EP antagonized these suppressive effects on food intake and weight gain for the first 3 d. However on d 4-7, β-EP no longer blocked these effects. Of note, the stimulatory effect of β-EP on feeding and its ability to antagonize MSH were specific for β-EP(1-31) and were not observed with β-EP(1-27). This study highlights the importance of understanding how the balance between α-MSH and β-EP is maintained and the potential role of differential POMC processing in regulating energy balance.
Topics: Animals; Body Weight; Eating; Male; Rats; Rats, Sprague-Dawley; alpha-MSH; beta-Endorphin
PubMed: 22778225
DOI: 10.1210/en.2012-1166 -
Aging Clinical and Experimental Research Jul 2020The purpose of this exploratory study was to examine the effects of Tai Chi on blood levels of beta endorphin (β-endorphin) and inflammatory markers in older adults... (Randomized Controlled Trial)
Randomized Controlled Trial
The purpose of this exploratory study was to examine the effects of Tai Chi on blood levels of beta endorphin (β-endorphin) and inflammatory markers in older adults with chronic pain. Forty community-dwelling older adults with chronic pain were randomized to Tai Chi or light physical exercise, and each offered twice weekly for 12 weeks. Following the 12-week intervention, neither Tai Chi nor light physical exercise changed levels of β-endorphin and inflammatory markers. However, in older adults who completed 70% or more classes, Tai Chi significantly lowered levels of β-endorphin (p < 0.05), whereas light physical exercise did not change levels of β-endorphin. The results suggest that Tai Chi may reduce levels of β-endorphin in older adults with chronic pain. Future studies are needed to better understand the role of the opioid analgesic system and immune system in regulating pain with aging and the long-term effects of Tai Chi on pain-related biomarkers.
Topics: Aged; Aged, 80 and over; Biomarkers; Chronic Pain; Exercise; Female; Humans; Independent Living; Inflammation; Male; Tai Ji; beta-Endorphin
PubMed: 31432432
DOI: 10.1007/s40520-019-01316-1 -
Neuropsychopharmacology : Official... Aug 2015Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed....
Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable 'cafeteria diet'. When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wild types, even though the length of bouts was similar to that of wild types, a pattern that suggests diminished food motivation. Conversely, BEND KOs did not differ from wild types in the number of licking bouts, even though these bouts were shorter in length, suggesting that they experienced the sucrose as being less palatable. In addition, licking responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body weights compared with wild types on chow diet and attenuated weight gain when fed cafeteria diet. Based on this and related findings, we suggest endogenous enkephalins primarily set a background motivational tone regulating feeding behavior, whereas β-endorphin underlies orosensory reward in high need states or when the stimulus is especially valuable. Overall, these studies emphasize complex interplays between endogenous opioid peptides targeting μ-receptors, such as enkephalins and endorphins, underlying the regulation of feeding and body weight that might explain the poor efficacy of drugs that generally target μ-opioid receptors in the long-term control of appetite and body weight.
Topics: Animals; Appetite; Body Weight; Case-Control Studies; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking Behavior; Enkephalins; Feeding Behavior; Female; Food Deprivation; Male; Mice; Mice, Knockout; Obesity; Protein Precursors; Sucrose; beta-Endorphin
PubMed: 25754760
DOI: 10.1038/npp.2015.67 -
Frontiers in Immunology 2022Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates -aconitate to produce...
Inflammation plays an important role in the occurrence and development of neuropathic pain. Immune-responsive gene 1 (IRG1) decarboxylates -aconitate to produce itaconate in the mitochondria. Itaconate serves as an immunomodulator of macrophages and represses inflammation in infectious diseases. Recently, a study showed that an itaconate derivative inhibits neuroinflammation and reduces chronic pain in mice. However, the function and molecular mechanisms of endogenous itaconate in neuropathic pain have not been fullyelucidated. In this study, the content of itaconate in the ipsilateral spinal cord after nerve-injured mice was detected with mass spectrometry. The mouse was constructed to determine the role of endogenous itaconate in the chronic constriction nerve injury (CCI) model. The analgesic effect of exogenous itaconate was assessed with intraperitoneal and intrathecal administration in both male and female CCI mice. The spinal application of 4-OI also reduced the evoked responses of wide dynamic range neurons in CCI mice. The potential analgesic mechanism of itaconate was explored through molecular biology experiments and verified in Interleukin mice. We found the levels of itaconate and IRG1 in the spinal cord significantly increased after CCI. deficiency aggravated the mechanical and heat hypersensitivity, while the exogenous administration of the itaconate derivative 4-OI alleviated the neuropathic pain in male and female CCI mice. Mechanistically, the treatment of 4-OI increased the level of IL-10 and activates STAT3/β-endorphin pathway in the spinal cord, and the analgesia effect of itaconate was impaired in mice. Finally, we showed that the upregulation of IL-10 induced by 4-OI was mainly from spinal neurons through Nrf2 pathway. This study demonstrated the analgesic effect of endogenous and exogenous itaconate in the neuropathic pain model, suggesting that the spinal IL-10/STAT3/β-endorphin pathway might mediate the analgesia effect of itaconate.
Topics: Female; Mice; Male; Animals; Interleukin-10; beta-Endorphin; Neuralgia; Analgesics; Inflammation; Hydro-Lyases
PubMed: 36311727
DOI: 10.3389/fimmu.2022.1012442 -
International Journal of Molecular... Sep 2022Pain is a worldwide public health problem and its treatment is still a challenge since clinically available drugs do not completely reverse chronic painful states or...
Pain is a worldwide public health problem and its treatment is still a challenge since clinically available drugs do not completely reverse chronic painful states or induce undesirable effects. Crotalphine is a 14 amino acids synthetic peptide that induces a potent and long-lasting analgesic effect on acute and chronic pain models, peripherally mediated by the endogenous release of dynorphin A and the desensitization of the transient receptor potential ankyrin 1 (TRPA1) receptor. However, the effects of crotalphine on the central nervous system (CNS) and the signaling pathway have not been investigated. Thus, the central effect of crotalphine was evaluated on the partial sciatic nerve ligation (PSNL)-induced chronic neuropathic pain model. Crotalphine (100 µg/kg, p.o.)-induced analgesia on the 14th day after surgery lasting up to 24 h after administration. This effect was prevented by intrathecal administration of CB1 (AM251) or CB2 (AM630) cannabinoid receptor antagonists. Besides that, crotalphine-induced analgesia was reversed by CTOP, nor-BNI, and naltrindole, antagonists of , , and -opioid receptors, respectively, and also by the specific antibodies for β-endorphin, dynorphin-A, and met-enkephalin. Likewise, the analgesic effect of crotalphine was blocked by the intrathecal administration of minocycline, an inhibitor of microglial activation and proliferation. Additionally, crotalphine decreased the PSNL-induced IL-6 release in the spinal cord. Importantly, in vitro, crotalphine inhibited LPS-induced CD86 expression and upregulated CD206 expression in BV-2 cells, demonstrating a polarization of microglial cells towards the M2 phenotype. These results demonstrated that crotalphine, besides activating opioid and cannabinoid analgesic systems, impairs central neuroinflammation, confirming the neuromodulatory mechanism involved in the crotalphine analgesic effect.
Topics: Amino Acids; Analgesia; Analgesics; Analgesics, Opioid; Ankyrins; Cannabinoid Receptor Antagonists; Cannabinoids; Dynorphins; Enkephalin, Methionine; Humans; Interleukin-6; Lipopolysaccharides; Microglia; Minocycline; Neuralgia; Peptides; Phenotype; Receptors, Opioid; Spinal Cord; beta-Endorphin
PubMed: 36232883
DOI: 10.3390/ijms231911571 -
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 -
Fertility and Sterility Nov 1990beta-Endorphin has a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. We have reviewed the evidence pointing to an alteration... (Review)
Review
beta-Endorphin has a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. We have reviewed the evidence pointing to an alteration in this neuropeptide that may contribute to the pathogenesis of various reproductive dysfunctions. Elevated or high levels of beta-endorphin have been associated with exercise-associated amenorrhea, stress-associated amenorrhea, and polycystic ovarian syndrome. Depressed or low levels of beta-endorphin have been associated with PMS and menopause. Alterations in the levels of beta-endorphin may change the pulsatile release of GnRH via noradrenergic and/or dopaminergic pathways. We have primarily focused on beta-endorphin as representative of the endogenous opioid peptides, but other opioid peptides may also contribute to the pathogenesis of various types of reproductive dysfunction. Perhaps it will become possible to characterize and hone our understanding of the function of beta-endorphin and the other substances composing the endogenous opioid peptides. A better understanding of their role in physiological as well as pathophysiological processes may allow for the development of rational approaches to the treatment of specific disorders pertaining to reproduction. Many questions remain unanswered. Among the most relevant are: what is the precise mechanism of action by which beta-endorphin exerts its influence on pulsatile GnRH release? Is there a functional relationship between CNS and peripheral (serum) levels of beta-endorphin? Are the detected changes in beta-endorphin levels merely associated, or are they a cause of a particular disorder? Since it took almost 40 years between the time prostaglandins were first discovered and eventual realization of their clinical application, it may take some time before the beta-endorphin story is complete.
Topics: Female; Humans; Infertility, Female; Reproduction; beta-Endorphin
PubMed: 2226908
DOI: 10.1016/s0015-0282(16)53928-4