Plasma Β-endorphin Concentrations Research Articles

Characterizing the opioidergic mechanisms of repetitive transcranial magnetic stimulation-induced analgesia: a randomized controlled trial.

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 β-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.

The Effects of Androstenone on the Plasma Serotonin, β-Endorphin, and Cortisol Concentrations in Thoroughbred Horses.

Simple SummaryThe development of horse managing tools is needed to prevent accidents and to improve welfare for domestic horses because the safety hazards for people who are exposed to horses are well documented. Androstenone, a pheromone secreted from boars, changes the behavior of dogs to become less excited. In horses, a previous study showed that a specific receptor for androstenone was expressed in the vomeronasal organ and nasal cavity. Horses treated with androstenone also showed more compliant behaviors. Thus, this study was conducted to investigate the mechanism of androstenone for changing horse behaviors. The change in the plasma concentrations of serotonin, β-endorphin, and cortisol in response to the treatment of androstenone was evaluated using an immunoassay. The results of this study demonstrated that androstenone may control the neuroendocrine system of horses, resulting in behavioral changes. This is the first work that studies the mechanism of pheromone treatment in horses and can be applied for further study about the effect of pheromone therapy on horses.Androstenone influences the changing behaviors of animals. Previous studies discovered that an androstenone receptor was expressed in horses and treatment with androstenone induced horses to be more compliant. As changes in the level of neuroendocrine factors result in animal behavioral changes, the objective of the study was to monitor the changes in the concentrations of 5-HT, β-endorphin, and cortisol in response to androstenone. Eight thoroughbred horses (five mares and three geldings) were treated with androstenone diluted in jojoba oil (10 µg/mL) and only oil for a control cross-overly. A handler applied the treatments to the horses′ nostril and rubbed for 5 s. Blood samples were collected before, 15, 30, and 60 min after each treatment. The concentrations of each neurotransmitter were analyzed by enzyme-linked immunosorbent assay. The concentrations of each neurotransmitter after the treatment were compared to its baseline concentration. The concentration of 5-HT of the androstenone-treated horses remained consistent throughout the experiment, while the concentration of the control group significantly decreased over time. The plasma concentration of β-endorphin in the androstenone-treated group also remained constant, whereas the concentration increased in the control group. Cortisol levels did not change in either the treated or untreated groups. An androstenone treatment triggers changes in the secretion of 5-HT and β-endorphin in horses.

The Relationship Between Antipsychotic Treatment and Plasma β-Endorphin Concentration in Patients with Schizophrenia.

ObjectiveSome studies indicate the presence of elevated opioid levels in cases of schizophrenia and their relationship with negative symptoms. The pathogenesis of schizophrenia may be associated with an imbalance in the modulatory effect of opioids on the dopaminergic system. The aim of the study was to identify the association between β-endorphin (BE) concentration and the outcome of short-term schizophrenia treatment.MethodsWe examined 49 patients hospitalized due to exacerbation of schizophrenia symptoms and 47 controls without schizophrenia. The severity of psychopathological symptoms was evaluated using Positive and Negative Syndrome Scale (PANSS) at the onset of hospitalization, and after four, six and ten weeks of treatment. Patients were classified into negative (NEG) and mixed (M) psychopathological subtypes according to the PANSS composite index. Β-endorphin (BE) plasma concentrations were assessed in all participants; in patients on inclusion to the study and after six weeks of treatment.ResultsThe patients with schizophrenia demonstrated higher BE levels than controls. During six-week antipsychotic treatment, BE concentration significantly increased in both NEG (p=0.000) and M (p=0.007), and positive symptoms were effectively reduced. In the NEG group, the prevalence of negative symptoms decreased only transiently and returned to approximately baseline values after 10 weeks (p=0.268). In the M patients, the prevalence of negative symptoms increased gradually (p=0.001), with more severe positive and, notably, negative symptoms correlating with higher BE2 concentrations at the 10-week assessment (R= 0.47, p= 0.0135 vs R= 0.74, p=0.0000). In both NEG and M, a greater rise in BE2 level correlated with a lower composite index during treatment.ConclusionPatients with schizophrenia demonstrate higher BE levels compared to controls. These changes in BE concentration during antipsychotic treatment could reflect the interaction between dopaminergic transmission and endogenous opioids. A rise in BE level following effective antipsychotic therapy could be a potential predictor of persisting negative symptoms.

Plasma β-Endorphin Concentration and Antipsychotic Treatment Outcome in Schizophrenia: 1-Year Follow-Up.

BackgroundIncreased 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/MethodsThe 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. β-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.ResultsPatients 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).ConclusionsIndividuals 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.

Plasma B-endorphin and cortisol profiles around periparturient period in Friesian Cattle suffering from reproductive disorders in Egypt

The present study aimed to determine plasma β-endorphin and cortisol concentrations in cattle with reproductive disorders (dystocia and retained placenta) and weakness body condition score during periparturient period. Stress may cause an overproduction of beta-endorphins and free radicals. Twenty multiparous Friesian cows weighing 400–650 kg aged 6-10 years and between (3-8) parities at late pregnancy period was used for two months before parturition. From ten days before the expected birth date the birth canal of each animal was monitored by rectal and vaginal palpations, and the body temperature was checked daily to predict the probable time of parturition. Animals were divided into four groups according to parturition disorders’ five animals in each one. First group delivered spontaneously at term with no obstetrical assistance(A), second group delivery was at term but was accompanied by dystocia(B), third group delivery was at term but was accompanied by retained placenta(C), and fourth group delivery was at term but animals showed weakness body condition score (D). Results illustrated that Plasma β-endorphin level in Friesian cattle during pregnancy state increased gradually through gestation period. It reaches its highest level during the third trimester due to stressful state. Also, it reaches its peak at zero time of parturition by appearing its analgesic action. Meanwhile, it decreases gradually towards re-establishment of ovarian cycle. Generally, cows suffering reproductive disorders had a clear impact on blood plasma β-endorphin concentration around parturition process.

Plasma Β-Endorphin and Cortisol Profiles around Periparturient Period at Stressful Conditions in Egyptian Buffalo

<p>The study determined the level of plasma β-endorphin and cortisol concentrations in peripheral blood circulation of buffalo cows suffering from reproductive disorders (dystocia and retained placenta) and weakness body condition score during periparturient period. Twenty multi-parous Egyptian buffalo cows at late pregnancy period were used for two months before parturition. β-endorphin concentrations were higher in buffalo suffering from reproductive disorders groups. Whereas, β-endorphin concentrations were 134.9±4.8 for retained placenta, 121.3±4.9 for dystocia, 114.2±8.4 for weakness and 113.5±6.5 pg/ml for control. In the closer period around parturition both of plasma β-endorphin and cortisol followed the same trend toward a gradually increased values during -2,-1days and zero time in all groups. A concomitant trend was noticed in β-endorphin and cortisol concentrations in postpartum period with reduce values were observed in all groups after parturition continued for month or more. Buffalo suffering from reproductive disorders were showed a high relative values in β-endorphin and cortisol concentrations. A significant differences (P<0.01) were observed between the experimental groups. Generally, buffaloes suffering reproductive disorders had a clear impact on blood plasma β-endorphin concentration around parturition process.</p><p>The aim of this study was to determine the relationship between various reproductive disorders as a stress factors with plasma β–endorphin and cortisol in buffalo cows around parturition and changes in these parameters could be used as an objective measure of the stress associated labour. Stress has been hypothesized to be a cause of impaired reproductive efficiency. Stress may cause an overproduction of beta-endorphins and free radicals</p>

Perspectives on Endogenous Opioids in Birds.

The present review summarizes the state of knowledge of endogenous opioids in birds. Endogenous opioid peptides acts in a neuromodulatory, hormonal and paracrine manner to mediate analgesic and other physiological functions. These peptides act through specific G-protein coupled receptors. Opioid receptors consist of a family of four closely-related proteins. The three types of opioid receptors are the mu (MOR or μ), delta (DOR or δ), and kappa (KOR or κ) opioid receptor proteins. The role of the fourth member of the opioid receptor family, the nociceptin or orphanin FQ receptor (ORL), is not clear. The ligands for opioid receptors are: β –endorphin (MOR), Met- enkephalin, Leu-enkephalin (DOR) and dynorphin (KOR), together with probably endomorphins 1 and 2. In spite of long history of research on endogenous opioid peptides, there are no studies of endogenous opioids per se in wild birds and few in poultry species. β-endorphin is present in all birds investigated and there is close agreement between the structures of β-endorphin in different birds. Plasma concentrations of β-endorphin are increased by ether stress in geese. There is evidence that β-endorphin plays a role in the control of luteinizing hormone release in chickens. Met-enkephalin is present in tissues such as the retina, hypothalamus, pituitary gland, and adrenals together with circulation of birds. Stresses such as crowding and withholding water increase circulating concentrations of Met-enkephalin in chickens. The structures of chicken dynorphin A and B have been deduced from cDNA. What is missing are comprehensive studies of plasma concentrations and expression of the full array of endogenous opioids in multiple avian species under different situations. Also, what is not known is the extent to which circulating or locally released or intra-cellular Met-enkephalin influence physiological process in birds. Thus, there is considerable scope for investigation of the physiology of endogenous opioids in birds.

Relationships Between Self-Injurious Behaviors, Pain Reactivity, and β-Endorphin in Children and Adolescents With Autism.

Autism and certain associated behaviors including self-injurious behaviors (SIB) and atypical pain reactivity have been hypothesized to result from excessive opioid activity. The objective of this study was to examine the relationships between SIB, pain reactivity, and β-endorphin levels in autism. Study participants were recruited between 2007 and 2012 from day care centers and included 74 children and adolescents diagnosed with autism (according to DSM-IV-TR, ICD-10, and CFTMEA) and intellectual disability. Behavioral pain reactivity and SIB were assessed in 3 observational situations (parents at home, 2 caregivers at day care center, a nurse and child psychiatrist during blood drawing) using validated quantitative and qualitative scales. Plasma β-endorphin concentrations were measured in 57 participants using 2 different immunoassay methods. A high proportion of individuals with autism displayed SIB (50.0% and 70.3% according to parental and caregiver observation, respectively). The most frequent types of SIB were head banging and hand biting. An absence or decrease of overall behavioral pain reactivity was observed in 68.6% and 34.2% of individuals with autism according to parental and caregiver observation, respectively. Those individuals with hyporeactivity to daily life accidental painful stimuli displayed higher rates of self-biting (P < .01, parental evaluation). No significant correlations were observed between β-endorphin level and SIB or pain reactivity assessed in any of the 3 observational situations. The absence of any observed relationships between β-endorphin level and SIB or pain reactivity and the conflicting results of prior opioid studies in autism tend to undermine support for the opioid theory of autism. New perspectives are discussed regarding the relationships found in this study between SIB and hyporeactivity to pain.

Influence of training and competitive sessions on peripheral β-endorphin levels in training show jumping horses.

Aim:To investigate the effects of training sessions on circulating β-endorphin changes in sport horses before and after competition and to ascertain whether competition would affect this response.Materials and Methods:A total of 24 trained jumping horses were randomly assigned to one of two training groups: Group A (competing) and Group B (not competing). To determined plasma β-endorphin concentrations, two pre- and post-competition training weeks at aerobic workout and two competitive show jumping event days at anaerobic workout were measured before, 5 and 30 min after exercise. Exercise intensity is described using lactate concentrations and heart rate. The circuit design, intensity, and duration of training sessions were the same for both groups.Results:In Group A, one-way analysis of variance for repeated measures (RM-ANOVA) showed significant effects of exercise on β-endorphin changes (F=14.41; p<0.001), only in the post-competition training sessions, while in Group B showed no significant effects. Two-way RM-ANOVA showed, after post-competition training sessions, a significant difference between Group A and Group B (F=6.235; p=0.023), with higher β-endorphin changes in Group A, compared to Group B. During the competitive show jumping sessions, one-way RM ANOVA showed significant effects of exercise on β-endorphin changes (F=51.10; p<0.001). The statistical analysis, in Group A, showed a significant difference between post-competition training and competitive exercise (F=6.32; p=0.024) with higher β-endorphin values in competitive sessions compared to those of post-competition training.Conclusion:Lactate concentrations seem to be the main factors being correlated with the raise of β-endorphin during anaerobic exercise of competitive events. Exercise of low intensity, as well as that one of training sessions, does not appear to stimulate a significant increased release of β-endorphin and it may depend on the duration of the exercise program. Moreover, the responses during exercise in the course of post-competition training sessions seem to be significantly different from those the pre-competition training. These data show that the preliminary competitive stress induced additional significant changes of β-endorphin pattern. It would reflect the need of a long-lasting modulation of fatigue and pain perception related to the effect of an additional physical and mental effort for the consecutive competitive and training sessions.

Metformin increases pressure pain threshold in lean women with polycystic ovary syndrome.

BackgroundDespite the strong preclinical rationale, there are only very few data considering the utility of metformin as a potential pain therapeutic in humans. The aim of this study was to determine the association between metformin therapy and pressure pain threshold (PPT) in lean women with polycystic ovary syndrome (PCOS). We hypothesized that metformin therapy in lean PCOS women increases PPT.Materials and methodsTwenty-seven lean PCOS women with free androgen index phenotype >5 and 18 lean healthy controls were enrolled in the study. Fifteen of the PCOS women were randomly assigned to be treated with metformin 1,500 mg daily for 6 months. PPT and plasma β-endorphin levels were measured in all women at the beginning of the study and after 6 months of observation.ResultsWe observed an increase in PPT values measured on deltoid and trapezius muscle in the PCOS with metformin group after 6 months of metformin administration (4.81±0.88 kg/cm2, P<0.001 on deltoid muscle, and 5.71±1.16 kg/cm2 on trapezius muscle). We did not observe any significant changes in PPT values in the PCOS without treatment group and in controls. We did not observe any significant changes in serum β-endorphin levels in any studied groups during the 6-month observation.ConclusionWe conclude that metformin therapy increases PPT in lean PCOS women, without affecting plasma β-endorphin concentration. Our results may suggest the potential role of metformin in pain therapy. We propose that larger, randomized studies on metformin impact on pain perception should be performed.

Odors hedonic judgment in patients with schizophrenia. Influence of negative symptoms and β-endorphin levels

IntroductionThe relationship between olfactory and emotional processing is an area of increasing interest in schizophrenia research.ObjectivesOlfactory identification deficits are well described in schizophrenia while the results for pleasantness ratings remain unclear.AimsEvaluation of odor identification and hedonic judgment related to severity of negative symptoms and β-endorphin concentration.MethodsFifty outpatients with schizophrenia were included in the study: 25 with negative symptoms (PN) and 25 without predominant negative symptoms (P). They were compared with 23 healthy individuals. In all study groups University of Pennsylvania Smell Identification Test (UPSIT) and odor hedonic evaluation were performed. Clinical symptoms severity was evaluated using PANSS. Plasma concentrations of β-endorphin were assayed in all participants.ResultsPN made more odor identification errors than controls (P = 0.000) and P sample (P = 0.001). Hedonic judgments of unpleasant odors were significantly more pleasant in PN sample than in P (P = 0.03) and controls (P = 0.041). PN had significantly higher concentration of β-endorphin than P sample (P = 0.014) and controls (P = 0.009). No relationship between β-endorphin concentration and odors identification and odor hedonic judgment was found in both patient samples and controls.ConclusionsIncreased level of β-endorphin is related to predominance of negative symptoms but probably it is not involved in olfactory identification performance and hedonic judgment in schizophrenia. Patients with predominant negative symptoms revealed different pattern of pleasantness rating – they experience unpleasant odors as more pleasant. Alterations in smell identification and hedonic judgment could be differentially expressed in some subtypes of schizophrenia.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.

BackgroundOpioid receptors (OR) are involved in myocardial late preconditioning (LPC) induced by morphine and δ1-opioid receptor (δ1-OR) agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists.MethodsMale Wistar rats were randomly allocated to four groups (each group n = 8). Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal) 10 minutes prior to LPC (Nal-LPC; trigger phase) or 10 min prior to sustained ischemia (LPC-Nal; mediation phase).ResultsLPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001). Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC). 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas μ-opioid receptor (μ-OR) and κ-opioid receptor (κ-OR) were not. Plasma concentrations of β-endorphin and leu-enkephalin but not dynorphin were increased by LPC.ConclusionIschemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

Effect of intravenous general anaesthesia with epidural block on the expression of pre-endogenous opioid peptide genes.

To measure the plasma concentrations of three endogenous opioid peptides and the levels of preproenkephalin (PPE) and preprodynorphin (PPD) mRNA in peripheral blood lymphocytes of patients during scheduled surgery performed under intravenous general anaesthesia combined with an epidural block. Patients were anaesthetized and arterial blood was collected at 0 (baseline), 20, 40, 60, and 80 min during surgery. The plasma concentrations of β-endorphin, leucine-enkephalin and dynorphin A were measured using radioimmunoassay. Reverse transcription-polymerase chain reaction was used to measure the levels of PPD and PPE mRNA in peripheral blood lymphocytes collected during surgery. Fifteen patients participated in this prospective study. The plasma concentrations of β-endorphin were significantly lower at all time-points compared with the baseline value. The plasma concentrations of leucine-enkephalin and dynorphin A were significantly lower at 40, 60, and 80 min compared with baseline. The PPD/β-actin ratio was significantly lower at 80 min compared with baseline, while the PPE/β-actin ratio showed no significant change. The level of mRNA from two pre-endogenous opioid peptide genes either decreased or remained unchanged during surgery under intravenous general anaesthesia with epidural block, suggesting that patients remained pain free during surgery.

Changes in blood parameters and electroencephalogram of cattle as affected by different stunning and slaughter methods in cattle

The present study aimed to provide a comparative analysis of the effects of penetrative stunning, non-penetrative stunning and post-slaughter stunning on biochemical parameters and electroencephalogram (EEG) associated with stress in heifers and steers. Ten animals were assigned to each of the following four treatment groups: (1) animals were subjected to conventional halal slaughter (a clean incision through the structures on the ventral neck at the approximate level of vertebrae C2–C3 – the trachea, oesophagus, carotid arteries and jugular veins) and post-cut penetrating mechanical stun within 10–20 s of the halal cut (U); (2) high-power non-penetrating mechanical stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (HPNP); (3) low-power non-penetrating mechanical percussive stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (LPNP); and (4) penetrative stunning using a captive-bolt pistol humane killer, followed by conventional halal slaughter (P). For each animal, blood samples and electroencephalogram recordings were taken before stunning, post-stunning (if applicable) and post-slaughter, and plasma concentrations of cortisol, adrenocorticotrophic hormone (ACTH), adrenaline, noradrenaline and β-endorphin were determined. Irrespective of the stunning method, except for percentage change in plasma concentrations of noradrenaline, the values of blood parameters attained before and after stunning were not significantly different. The plasma noradrenaline concentration of the HPNP animals was significantly elevated following stunning. Following slaughter, the percentage change of plasma ACTH concentration in the P animals was significantly elevated. Neither stunning method nor sampling time had a significant effect on plasma β-endorphin concentration. On the basis of the EEG results, penetrative stunning seemed to be better in maximising the possibility of post-stunning insensibility, whereas U animals appeared to demonstrate an evident increase in EEG activity which is consistent with the presence of post-slaughter noxious stimuli associated with tissue cut and injury. The U animals had consistently higher, if not the highest, RMS values than did other stunned animals. This indicates a degree of EEG changes associated with stress and pain. On the basis of EEG data, our results suggested that penetrative stunning would be the most reliable method of ensuring insensibility and minimising pain. However, at slaughter, the P animals showed a dramatic elevation in the percentage change of circulating ACTH, suggesting physiological stress response. On a cautionary note, the results are not unequivocal, and it may be that the range of analyses available to researchers at this point of time are not sufficiently specific to allow definitive conclusions to be drawn.

β-endorphin degradation and the individual reactivity to traumatic stress

Reactivity to traumatic stress varies between individuals and only a minority of those exposed to trauma develops stress-induced psychopathologies. Currently extensive effort is made to unravel the specific mechanisms predisposing to vulnerability vs. resilience to stress. We investigated in rats the role of β-endorphin metabolism in vulnerability to acute traumatic stress. Responders (showing extreme anxiety; n=7) and resilient non-responders (not differing from the non-stressed individuals; n=8) to traumatic foot-shock stress were compared for their blood levels of stress hormones as well as brain levels and activity of two opioid-degrading enzymes. β-endorphin is a substrate to insulin degrading enzyme, which also degrades insulin. Therefore, the effects of insulin application on behavioral and hormonal responses and on β-endorphin degradation were tested. Pre- and post-stress levels of serum corticosterone, and post-stress plasma β-endorphin concentration differentiated between the responders and the non-responders. In brain, responders showed enhanced degradation rates of β-endorphin, assessed by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS), in hippocampal and amygdalar slices as compared to non-responders. Application of insulin to the amygdala, prior to exposure to traumatic stress, reduced post-stress anxiety and serum corticosterone levels only in the responders. In parallel, amygdalar β-endorphin degradation rate was also reduced by insulin. These results suggest that slowing down β-endorphin degradation rate may constitute an integral part of the normal stress-response, upon a failure of which an extreme anxiety develops. Modulation of opioid degradation may thus present a potential novel target for interference with extreme anxiety.

Effectiveness of electroacupuncture analgesia compared with opioid administration in a dog model: a pilot study

Although opioid analgesics are the usual drugs to treat post-surgical pain, acupuncture has also been demonstrated to relieve various pain syndromes. The present pilot study aims to investigate the efficacy of electroacupuncture compared with a conventional opioid compound, butorphanol, for postoperative pain treatment in dogs undergoing elective ovariohysterectomy. Twelve dogs were randomly allocated into two groups. Dogs received either electroacupuncture stimulation (16 and 43 Hz) at Shen Shu, Chang Shu, He Gu, Tai Yuan, Zu San Li, Yang Ling Quan, and Bai Hui acupoints, while control dogs were treated with butorphanol. Cardiovascular and respiratory parameters were recorded for both groups during operation. Plasma β-endorphin concentrations were evaluated before surgery (baseline) and up to 24 h later. For each dog, pain was measured according to a dedicated subjective pain scoring system. Plasma β-endorphin levels in dogs receiving electroacupuncture increased significantly against baseline values after 1 and 3 h after surgery. Moreover, the end-tidal isoflurane concentration needed for second ovary traction was significantly lower in acupuncture-treated dogs than control animals. All animals having electroacupuncture experienced prolonged analgesia, over 24 h at least, while four out of six dogs treated with butorphanol needed post-surgical ketorolac and tramadol supplementation to their pain relief. The results obtained from the present investigation showed some evidence for electroacupuncture as an alternative technique to provide postoperative analgesia in dogs.

Effects of competitive and noncompetitive showjumping on total and free iodothyronines, β‐endorphin, ACTH and cortisol levels of horses

Limited knowledge exists about the differentiated effects of competitive and noncompetitive showjumping on thyroid function and relationships with hypothalamic-hypophysis-corticoadrenal hormones. To obtain preliminary data about differentiated effects of competitive and noncompetitive showjumping on total and free iodothyronines, β-endorphin, ACTH and cortisol of horses. Five trained healthy jumper horses were studied during competitive and noncompetitive showjumping, performed in the same circuit design over 10 fences of 1.10 m. Hormone levels before, 5 and 30 min post exercise were recorded. Serum iodothyronines and cortisol concentrations were measured in duplicate utilising EIA kits. Serum ACTH and plasma β-endorphin concentrations were analysed in duplicate utilising RIA kits. Two-way RM ANOVA was applied to test for effects of interaction between different type of session and time. Significant differences between post exercise and basal values were established using Bonferroni's multiple comparison test. A linear correlation analysis (Pearson's method) was performed to analyse the relationships between total and free iodothyronines and between iodothyronines and β-endorphin, ACTH and cortisol. In sampling times adopted no statistical different effects of type of session were recorded on hormone variables. Sampling time affected ACTH (F = 4.25; P < 0.02) and T(4) (F = 4.43; P < 0.02) post exercise changes. During the noncompetitive session, significant correlations existed between T(4) and β-endorphin (r = -0.56), ACTH (r = -0.65), between β-endorphin and ACTH (r = 0.52) and between T(3) and fT(3) (r = 0.72); during competition between β-endorphin and T(3) (r = -0.67), fT(3) (r = -0.59). These preliminary results could demonstrate correlations between thyroid hormones and β-endorphin response to showjumping, although no definitive conclusion can be produced concerning the relationships between HPA and thyroid function during exercise.

Pain Reactivity and Plasma β-Endorphin in Children and Adolescents with Autistic Disorder

BackgroundReports 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 β-endorphin levels and their relationship in a large group of individuals with autism.Methodology/Principal FindingsThe 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 β-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 (Δ 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 β-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/SignificanceThe greater heart rate response to venepuncture and the elevated plasma β-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.

Endocrine changes after experimental showjumping

The study was designed in order to gain a better understanding of whether the lack of competition stress and/or sampling time had an influence on circulating β-endorphin, adrenocorticotrophin (ACTH) and cortisol modifications after experimental showjumping sessions and to study the effects of fence height on hormone changes. Hormone levels were recorded before exercise in basal conditions and after warm-up, then 5 and 30 min post-exercise. Using a randomized crossover study design, six horses were studied during three experimental showjumping sessions over fences of different heights: 1.00 m (session 1), 1.10 m (session 2) and 1.20 m (session 3). The showjumping exercise did not modify plasma β-endorphin and serum ACTH concentrations after session 1, and tended only to maintain higher values than basal after both session 2 and session 3. The interaction fence height/time was not statistically significant for either β-endorphin or ACTH changes. Sampling time significantly affected both β-endorphin (F = 2.88; P < 0.04) and ACTH (F = 3.84; P < 0.01) changes. Serum cortisol levels were always higher than basal 5 min post-exercise, with levels falling at 30 min. The interaction fence height/time was not statistically significant, while sampling time significantly affected the results (F = 7.96; P < 0.0002). This study demonstrated no significant effects of fence height on β-endorphin, ACTH and cortisol changes. The sampling times adopted affected post-exercise changes in plasma β-endorphin, ACTH and cortisol and could have masked the effects of fence height on hormone modifications.

Sex Differences in Brain and Plasma β-Endorphin Content following Testosterone, Dihydrotestosterone and Estradiol Administration to Gonadectomized Rats

Aims: The present study aims at evaluating the effect of a 2-week treatment with testosterone (T), dihydrotestosterone (DHT) and estradiol valerate (E₂V) on brain and plasma β-endorphin (β-END) concentrations in gonadectomized rats of both sexes. Methods: Eight groups of female and 8 groups of male Wistar rats were included. For each sex, 1 group of gonad-intact and 1 group of gonadectomized rats were employed as controls (placebo). The other groups received subcutaneous T at the doses of 10 and 100 μg/kg/day (female rats) or 1 and 5 mg/kg/day (male rats). Subcutaneous DHT was administered at the doses of 1, 10, 100 μg/kg/day (female rats) or 0.1, 1 and 5 mg/kg/day (male rats). E₂V was administered subcutaneously at 0.05 mg/kg/day. β-END levels were measured in different brain areas and plasma. Results: Ovariectomy (OVX) induced a significant decrease in β-END in all brain areas analyzed as well as in plasma. Orchidectomy (OCX) reduced opioid concentration in the hypothalamus, anterior pituitary and neurointermediate lobe. In OVX rats, T replacement as well as E₂V significantly increased β-END concentration in all brain areas and in plasma. In the OCX group, T and E₂V did not influence β-END concentrations in different hypothalamic areas. However, they produced a significant rise in β-END levels in the hypothalamus, neurointermediate lobe, anterior pituitary and plasma. Conversely, DHT replacement did not affect β-END levels at any dose administered, either in males or females. Conclusions: The sensitivity of the endogenous opiatergic system to T administration seems to be sex-related. This effect is particularly evident in the brains of female animals where this endogenous endorphin elicits a much greater response than it does in males that have undergone gonadal steroid depletion and subsequent T replacement.