Prolonged disruption of plasma beta-endorphin dynamics following surgery

The purpose of the present study was to examine the effects of surgery on plasma beta-endorphin dynamics. Plasma beta-endorphin levels were measured by liquid chromatography/radioimmunoassay in seven patients undergoing elective surgery. Blood samples were obtained every 4 hr for two 24-hr periods: one beginning 48 hr before surgery and the other beginning 48 hr after surgery. Computer analysis of beta-endorphin levels as a function of clock time demonstrated a true circadian rhythm preoperatively with a mean of 28.0 +/- 5.9 pg/ml. In the postoperative period mean beta-endorphin levels were significantly elevated (85.6 +/- 20.7 pg/ml, P less than 0.005). Surgical procedures caused significant phase shifting in the grouped mean circadian rhythm of plasma beta-endorphin (mean = 2.4 hr). When the data was analyzed individually, plasma circadian rhythms were found to be totally abolished in the three patients with the longest operative times (mean = 3.8 hr) and significantly displaced in time in the remaining four patients. These prolonged alterations in plasma endogenous opioid peptide levels following surgery have not been previously reported, and should be considered in the management of the postsurgical patient.     

Streptozocin diabetes alters immunoreactive beta-endorphin levels and pain perception after 8 wk in female rats

Plasma, pituitary, and hypothalamic levels of the endogenous opioid peptide beta-endorphin were measured by radioimmunoassay and column chromatography in female rats 8 wk after the induction of diabetes with streptozocin (STZ) and in control female rats. In addition, pain perception was determined by measuring the latency to paw lick or jump after being placed on a hot plate. Plasma levels of immunoreactive beta-endorphin (IR-BE) were significantly reduced in STZ-induced diabetic female rats, as were the content and concentration of IR-BE in the neurointermediate lobe of the pituitary (NIL) and the content of IR-BE in the hypothalamus. The concentration but not the content of IR-BE in the anterior pituitary (AP) of the STZ-induced diabetic rats was increased significantly. Streptozocin-induced diabetes also resulted in a significant reduction in the total protein content of the AP, NIL, and hypothalamus. Column chromatography indicated that the decrease in IR-BE in the plasma, NIL, and hypothalamus represented a decrease in beta-endorphin, whereas the increase in IR-BE in the AP represented an increase in both beta-endorphin and beta-lipotropin. Diabetic animals consistently showed decreased latencies to paw lick or jump when subjected to hot-plate testing after 7 wk. These findings suggest that in female rats, central and peripheral endogenous opiate levels and tolerance to nociceptive thermal stimulation were diminished by 8 wk of chemically induced diabetes.     

Diabetes induced by streptozocin results in a decrease in immunoreactive beta-endorphin levels in the pituitary and hypothalamus of female rats

Immunoreactive beta-endorphin (IR-BE) was measured by radioimmunoassay in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL), and hypothalamus of female rats 4 wk after being made diabetic by a single injection of streptozocin (STZ). STZ-induced diabetes resulted in a significant reduction in the content and concentration of IR-BE in the AP and the content of IR-BE in the hypothalamus. Total hypothalamic protein was also significantly diminished. IR-BE levels in the NIL were unchanged. Column chromatography indicated that the reduction in IR-BE in the AP of the diabetic female rats represented a decrease in peptides that co-eluted with beta-endorphin and beta-lipotropin. In the hypothalamus, the reduction in IR-BE was represented solely by a decrease in a peptide co-eluting with beta-endorphin. Beta-lipotropin was not detectable in the hypothalami of control or diabetic female rats. These results suggest that, in the rat, diabetes may produce alterations in the mechanism(s) that regulate endogenous opiate levels in the pituitary and hypothalamus.     

Elevation of circulating beta-endorphin levels with concomitant depression of immune parameters after traumatic injury

Immunosuppression is frequently observed after traumatic injury, and is associated with the subsequent development of sepsis. Although a number of factors such as age, nutritional status, and the degree of injury have been related to the severity of the immunosuppression that occurs, the physiologic alterations leading to immunosuppression are not well defined. We hypothesized that changes in the endogenous opiate peptides, such as beta-endorphin, might contribute to changes in the immune system following injury. Levels of circulating beta-endorphin, responsiveness to the mitogen PHA, and the frequency of circulating T11, T4, and T8 cells were measured in trauma patients hospitalized in a surgical intensive care unit. beta-endorphin levels were elevated during the first 4 days after trauma (134.1 +/- 22.5 vs. 49.3 +/- 4.3 pg/ml, mean +/- S.E., patient vs. control; p less than 0.001). During the same time period patient PHA response (10,852 +/- 3,775 vs. 28,147 +/- 12,078; p less than 0.05), and the per cent of T4 positive (31.2 +/- 2.6 vs. 47.0 +/- 1.4; p less than 0.001) cells were lower than controls. These parameters were not significantly different from control values when measured at later times. Thus we conclude there is a temporal association of depressed immune parameters and elevated beta-endorphin levels after traumatic injury.     

Opioid peptide-expressing leukocytes: identification, recruitment, and simultaneously increasing inhibition of inflammatory pain

BACKGROUND: Inflammatory pain can be effectively controlled by an interaction of opioid receptors on peripheral sensory nerve terminals with opioid peptides released from immune cells upon stressful stimulation. To define the source of opioid peptide production, we sought to identify and quantify populations of opioid-containing cells during the course of Freund's complete adjuvant-induced hind paw inflammation in the rat. In parallel, we examined the development of stress-induced local analgesia in the paw. METHODS: At 2, 6, and 96 h after Freund's complete adjuvant inoculation, cells were characterized by flow cytometry using a monoclonal pan-opioid antibody (3E7) and antibodies against cell surface antigens and by immunohistochemistry using a polyclonal antibody to beta-endorphin. After magnetic cell sorting, the beta-endorphin content was quantified by radioimmunoassay. Pain responses before and after cold water swim stress were evaluated by paw pressure thresholds. RESULTS: In early inflammation, 66% of opioid peptide-producing (3E7+) leukocytes were HIS48+ granulocytes. In contrast, at later stages (96 h), the majority of 3E7+ immune cells were ED1+ monocytes or macrophages (73%). During the 4 days after Freund's complete adjuvant inoculation, the number of 3E7+ cells increased 5.6-fold (P < 0.001, Kruskal-Wallis test) and the beta-endorphin content in the paw multiplied 3.9-fold (P < 0.05, Kruskal-Wallis test). In parallel, cold water swim stress-induced analgesia increased by 160% (P < 0.01, analysis of variance). CONCLUSIONS: The degree of endogenous pain inhibition is proportional to the number of opioid peptide-producing cells, and distinct leukocyte lineages contribute to this function at different stages of inflammation. These mechanisms may be important for understanding pain in immunosuppressed states such as cancer, diabetes, or AIDS and for the design of novel therapeutic strategies in inflammatory diseases.     

Correlation of beta-endorphin and prostaglandin E2 levels in prostatic fluid of patients with chronic prostatitis with diagnosis and treatment response

PURPOSE: The chronic pelvic pain syndrome is a clinically defined symptom complex of unclear etiology. We have noted increased oxidative stress in the prostatic fluid of these patients, implying an active inflammatory response. Immune cells can produce the natural opioid beta-endorphin at the site of injury, which may modulate pain. We measured beta-endorphin and the inflammatory marker prostaglandin E2 in the expressed prostatic secretions of men with prostatitis, and correlated the results with symptoms. MATERIALS AND METHODS: Expressed prostatic secretions samples from 70 patients and 8 asymptomatic controls were collected and frozen. beta-Endorphin and prostaglandin E2 were measured by enzyme-linked immunosorbent assay. Results were stratified according to prostatitis category and compared in individuals before and after therapy. RESULTS: In symptomatic patients beta-endorphin and prostaglandin E2 were not significantly different in categories II, IIIa and IIIb expressed prostatic secretions but they were higher than in controls. The mean beta-endorphin level plus or minus standard error of mean in symptomatic patients was significantly higher (23.8 +/- 11 ng./ml. versus 8.7 +/- 4.7, p = 0.0001) and mean prostaglandin E2 was lower (6.01 +/- 2.9 ng./ml. versus 3.01 +/- 2.9, p = 0.001) after successful therapy with antibiotics or antioxidant phytotherapy, Prosta-Q (Farr Laboratories, Santa Clarita, California). CONCLUSIONS: We observed a correlation of higher prostaglandin E2 and lower beta-endorphin in symptomatic men with chronic prostatitis. Increased oxidative stress and inflammation may induce prostaglandin E2 production that would inhibit beta-endorphin release. Treatment with therapeutic agents that decrease oxidative stress, such as antibiotics and antioxidant phytotherapy, may function at least partially by increasing beta-endorphin and decreasing prostaglandin E2.     

Specific receptors for beta-endorphin on mesangial cells.

beta-Endorphin is an endogenous opioid considered to be a modulator of immune injury. We studied the binding of [125I]beta-endorphin on cultured rat mesangial cells at 4 and 37 degrees C. The results were analyzed by computer program (Ligand). Incubation of rat mesangial cells with unlabeled beta-endorphin displaced [125I]beta-endorphin in a concentration-dependent manner. The binding of [125I]beta-endorphin was not affected by either opiate agonists or antagonists. Saturation studies at 37 degrees C revealed that beta-endorphin binding was time dependent. Binding studies revealed the presence of a single class of high-affinity binding sites with an apparent Kd of 15.3 nM. The number of receptor sites was calculated as 8.48 x 10(5) sites/cell. Mesangial cells exposed to beta-endorphin (10(-6) M) for 48 h showed enhanced incorporation of [3H]thymidine when compared to untreated cells (control, 23,228 +/- 2,778 cpm/well vs. beta-endorphin, 44,887 +/- 4,259 cpm/well; p less than 0.01). Our results show that mesangial cells carry a specific receptor for beta-endorphin which may be linked to proliferation of mesangial cells.     

Immunoreactive ACTH, beta-endorphin, and cortisol levels in plasma following spinal manipulative therapy

This study examines the possibility of a humorally mediated analgesic response to spinal manipulative therapy by determination of plasma levels of beta-endorphin, adrenocorticotropic hormone (ACTH), and cortisol before and after intervention. Forty male subjects (20 symptomatic, 20 asymptomatic) were allocated into four equal groups. Two treatment groups were given spinal manipulative therapy, and two groups underwent a sham procedure. Blood samples were taken via indwelling butterfly needles pre- and postintervention in all four groups, and levels of immunoreactive ACTH, immunoreactive beta-endorphin, and cortisol determined by radioimmunoassay. No differences in ACTH or beta-endorphin were found between sham and treated groups, or between pre- and postintervention in any group; cortisol levels fell over the course of the study in all groups. The findings thus appear to exclude a humoral role for beta-endorphin in mediating the analgesic response to spinal manipulative therapy; in addition, they suggest that such therapy is not a stressor that activates the hypothalamo-pituitary-adrenal axis.     

Immunohistochemical localization of beta-endorphin in hyperplastic interstitial tissue of the human testis

The immunohistochemical localization of beta-endorphin in the normal testis (two patients) and in the pathologic testis (two cases of Sertoli Cell Only Syndrome, two cases of Klinefelter Syndrome, two cases of post-orchitis tubular sclero-hialinosis) was investigated. No beta-endorphin immunostaining was detected in the normal testis, while positive beta-endorphin immunostaining has been observed in pathologic tissues. These results indicate that, as in animals, beta-endorphin is present in human Leydig cells and may play a local role in regulating male reproductive function.     

Changes in beta-endorphin receptor on T-lymphocytes in burned patients and their significance]

The changes in beta-endorphin receptor on the peripheral T lymphocytes were assayed in 30 burned patients (average burn area 38.1 +/- 30.0% of TBSA) and 20 healthy volunteers with radioactive ligand I-beta-endorphin. Results showed that the binding sites of beta-endorphin receptor on T lymphocytes were significantly decreased in various degrees, while kd values were increased, in patients major burns. In patients with smaller burns, the above parameters showed no significant difference from the normal. There were also decreased binding sites when complications such as infection occurred.     

Plasma levels of vasoactive regulatory peptides in patients receiving regular hemodialysis treatment.

The fasting plasma levels of 10 vasoactive regulatory peptides were measured by radioimmunoassay in 23 stable patients with chronic renal failure receiving regular hemodialysis treatment (RDT) and compared with those of healthy controls. The plasma concentrations of arginine vasopressin, atrial natriuretic peptide, beta-endorphin, methionine-enkephalin, motilin, neuropeptide Y, substance P, and vasoactive intestinal peptide were increased. The plasma level of calcitonin gene-related peptide was not statistically different from that of the controls. The plasma concentration of gamma 2-melanocyte-stimulating hormone was lowered in the RDT-patients. The arterial blood pressure correlated with the plasma levels of motilin and neuropeptide Y. We conclude that patients with chronic renal failure receiving RDT have increased concentrations of 8 out of 10 measured vasoactive regulatory peptides. The elevated levels of vasoactive peptides may contribute to the adaptation of the cardiovascular system to impaired renal function.     

Minimal immunoreactive plasma beta-endorphin and decrease of cortisol at standard analgesia or different acupuncture techniques

BACKGROUND AND OBJECTIVE: Acupuncture has been claimed to be associated with activation of the endogenous antinociceptive system. The analgesic effects of acupuncture have been ascribed to beta-endorphin interacting with opioid receptors. However, firstly, the release of beta-endorphin into the blood has been proven to be induced by stress, i.e. under dysphoric conditions, and, secondly, if released under stress, beta-endorphin has been shown not to be analgesic. Our aim was to test whether beta-endorphin immunoreactive material is released into the cardiovascular compartment during acupuncture comparing the most frequently used types of acupuncture with standard pain treatment under apparently low stress conditions. METHODS: This prospective study included 15 male patients suffering from chronic low back pain. beta-Endorphin immunoreactive material and cortisol were measured in the plasma of patients who underwent, in random order, therapy according to a standard pain treatment, traditional Chinese acupuncture, sham acupuncture, electro acupuncture and electro acupuncture at non-acupuncture points before, at and after the treatment. Statistical analysis was performed using two-way ANOVA with repeated measures. RESULTS: A decrease in plasma cortisol concentration measured over the five treatment protocols was highly significant (P < 0.001). The beta-endorphin immunoreactive material concentrations in plasma were minimal at all times and in all treatment conditions. The influence of treatments by various acupuncture procedures on cortisol and beta-endorphin immunoreactive material plasma concentrations over the three time points was not significantly different. CONCLUSIONS: beta-endorphin immunoreactive material in blood is not released by any type of acupuncture as tested under low stress conditions.     

Beta-endorphin in serum and seminal plasma in infertile men

Aim:To access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups.Methods:Beta-endorphin was estimated in the serum and seminal plasma by enzyme-linked immunosorbent assay(ELISA)method in 80 infertile men equally divided into four groups:non-obstructive azoospermia(NOA),obstructive azoosper-mia(OA),congenital bilateral absent vas deferens(CBVAD)and asthenozoospermia.The results were compared tothose of 20 normozoospermic proven fertile men.Results:There was a decrease in the mean levels of beta-endorphin in the seminal plasma of all successive infertile groups(mean±SD:NOA 51.30±27.37,OA 51.88±9.47,CBAVD 20.36±13.39,asthenozoospermia 49.26±12.49 pg/mL,respectively)compared to the normozoospermicfertile control(87.23±29.55 pg/mL).This relation was not present in mean serum level of beta-endorphin betweenfour infertile groups(51.09±14.71,49.76±12.4,33.96±7.2,69.1±16.57 pg/mL,respectively)and the fertilecontrol group(49.26±31.32 pg/mL).The CBVAD group showed the lowest seminal plasma mean level of beta-endorphin.Testicular contribution of seminal beta-endorphin was estimated to be approximately 40%.Seminal beta-endorphin showed significant correlation with the sperm concentration(r=0.699,P=0.0188)and nonsignificantcorrelation with its serum level(r=0.375,P=0.185)or with the sperm motility percentage(r=0.470,P=0.899).Conclusion:The estimation of beta-endorphin alone is not conclusive to evaluate male reproduction as there aremany other opiates acting at the hypothalamic pituitary gonadal axis.(Asian J Androl 2006 Nov;8:709-712)     

Opioids modulate human neutrophil and lymphocyte function: thermal injury alters plasma beta-endorphin levels

To investigate the role of opioids in the acquired immune dysfunctional state that occurs after burns or trauma, plasma beta-endorphin levels were measured serially in nine severely burned patients, and the effect of four different opioids on normal neutrophil and lymphocyte function was quantitated. The rationale for these studies is that the neuroendocrine system appears capable of interacting with and modulating immune function. The plasma levels of beta-endorphin increased to higher than normal during the first 36 hours after burn (15 versus 3.4 pmol/L, p less than 0.05) but quickly returned toward normal. Morphine had the most profound effect on in vitro neutrophil function; it decreased neutrophil chemotaxis but increased neutrophil bactericidal activity for Staphylococcus aureus, as well as resting and zymosan-stimulated oxygen consumption. Other opioids (naloxone, met-enkephalin, and beta-endorphin) had no direct effect on neutrophil chemotaxis or bactericidal activity. Both naloxone and met-enkephalin increased neutrophil oxygen consumption in a dose-dependent fashion, whereas beta-endorphin impaired neutrophil oxygen consumption. None of the opioids altered resting lymphocyte blastogenesis. The only opioid that impaired the ability of normal lymphocytes to respond to mitogen stimulation at physiologically relevant doses was beta-endorphin. These results, documenting that beta-endorphin levels are altered after thermal injury and that opioids can modulate normal neutrophil and lymphocyte function in vitro, support the concept that changes in neuroendocrine activity may occur and potentially alter immune function.     

Ketamine stimulates secretion of beta-endorphin from a mouse pituitary cell line

BACKGROUND AND OBJECTIVES: beta-endorphin is an endogenous opioid that mediates pain-induced analgesia. Propofol inhibits in vitro secretion of beta-endorphin from a mouse pituitary cell line (AtT-20). We hypothesized that ketamine would also alter secretion of beta-endorphin. METHODS: AtT-20 cells were exposed to the intravenous anesthetic ketamine (10 to 40 micromol/L). Secretion of beta-endorphin was determined by enzyme-linked immunosorbent assay. Long-term effects were determined by exposing the cells to ketamine, allowing the cells to recover overnight, then stimulating the secretion of beta-endorphin. AtT-20 cells were stimulated with secretagogues to induce secretion of beta-endorphin. The effect of ketamine on stimulated secretion was determined. Cultures of AtT-20 cells were grown for 5 days in the presence of ketamine. Cell numbers were determined on each day. RESULTS: Ketamine increased secretion of beta-endorphin to levels that were up to 3 times greater than baseline secretion. Stimulation of beta-endorphin secretion by ketamine persisted into the subsequent day. Ketamine caused increased secretion from cells stimulated with secretagogues. Ketamine was not toxic to these cells; AtT-20 cells grew normally for 5 days in the presence of up to 40 micromol/L ketamine. CONCLUSIONS: Clinically relevant concentrations of ketamine stimulated both immediate and delayed secretion of beta-endorphin. This suggests that the prolonged analgesia observed in some clinical situations with ketamine could be in part caused by increased release of an endogenous opioid.     

Effects of a low-phosphorus, low-nitrogen diet supplemented with essential amino acids and ketoanalogues on serum beta-endorphin in chronic renal failure

The effects of a vegetarian low-protein, low-phosphorus diet supplemented with essential amino acids and ketoanalogues, on the serum beta-endorphin, growth hormone, parathyroid hormone, thyroid hormones (T3 and T4), pituitary TSH and total cortisol were studied in 12 male chronic uremics. beta-Endorphin decreased, as well as growth hormone. Parathyroid hormone and T3 improved significantly, reaching almost normal values. It is hypothesized that the correction of the beta-endorphin excess may account in part for the improvement of some endocrinological and metabolic effects exerted by this dietary treatment. The possible pathophysiological mechanisms which could explain the antiendorphinic action of this treatment in uremic patients are discussed, as well as the possible beneficial endocrine and metabolic effects exerted by the fall in circulating beta-endorphin.     

Relationship between release of beta-endorphin, cortisol, and trauma severity in children with blunt torso and extremity trauma

PURPOSE: To determine the levels of beta-endorphin and cortisol in children with multiple injuries and to determine whether there is any difference between and compare the severity of trauma and beta-endorphin and cortisol release as calculated using Pediatric Trauma Score (PTS). METHODS: During a 10-month period, 80 children with multiple injuries admitted to a University Hospital's Pediatric Surgery Department were studied. Blood samples were obtained immediately at admission and a PTS of each patient was calculated. The correlation between PTS and hormonal values were searched. The children were classified into two groups according to their PTS. Group 1 had PTS >8 and group 2 had PTS < or =8. The two groups were also compared with respect to their beta-endorphin and cortisol values. RESULTS: There was a linear correlation between beta-endorphin and cortisol values and the injury severity. The levels were higher in the patients with more severe injuries. There were 60 patients in group 1 and 20 patients in group 2. Their ages were 9.2 +/- 4.1 and 9.7 +/- 4.2 years, respectively (p > 0.05). The mean PTS for group 1 patients was 11 +/- 0.8 and for group 2 patients was 7.4 +/- 1.2 (p < 0.001). The mean plasma beta-endorphin concentrations were 124.4 +/- 114.4 pg/mL in group 1 patients and 261.6 +/- 231.2 pg/mL in group 2 (p < 0.001). The respective plasma cortisol concentrations in the two groups were 22.5 +/- 10.3 microg/dL and 30.8 +/- 17.2 microg/dL (p < 0.05), respectively. CONCLUSIONS: The results of this study show that the plasma beta-endorphin and cortisol levels are elevated in children after blunt trauma and the degree of elevation is related to the injury severity.     

beta-Endorphin induces general anaesthesia by an interaction with opiate receptors

beta-endorphin, administered into the cerebral ventricles of rats, provokes a sequence of behavioural and electroencephalographic (EEG) responses similar to those observed with general anaesthetics used clinically. Initial behavioural and EEG excitation, motor incoordination and exaggerated responsiveness to sensory stimuli are followed by a stage of rigid immobility with maintenance of local reflexes (withdrawal, corneal) and EEG arousal in response to stimulation. Finally, there is immobility associated with both EEG and behavioural unresponsiveness to severely noxious stimuli. Such a state of unconsciousness with complete analgesia defines general anaesthesia. This state was completely and rapidly reversed by the specific opiate antagonist, naloxone. The induction of general anaesthesia by a water-soluble neurohormonal peptide acting at specific receptor sites has important implications for traditional theories of anaesthesia.     

Increase of beta-endorphin levels in cerebrospinal fluid but not in plasma in patients with cerebral infarction

beta-Endorphin was measured in cerebrospinal fluid (CSF) and plasma in patients with cerebral infarction at acute (4 to 48 hours) and chronic (1 month) stages. Only CSF samples obtained in the acute stage showed beta-endorphin values that were statistically higher than those measured in a control population. This finding suggests that infarction at its acute stage gives rise to an increased release of beta-endorphin. Such a mechanism is consistent with the possibility that the reported therapeutic effect of naloxone in cerebral ischemic lesions may result in part from the antagonism of the centrally released endorphin, beta-endorphin.     

The patterns of stress response in patients undergoing thyroid surgery under acupuncture anaesthesia in China

The patterns of catecholamines (adrenaline and noradrenaline), peptide hormones (adrenocorticotropic hormone, antidiuretic hormone, beta-endorphin, growth hormone and prolactin), hydrocortisone (cortisol) and those of immunoglobulins (IgA, IgG and IgM) and total and differential leucocyte counts in the peripheral blood were investigated during and for 6 days after thyroid surgery in 20 patients (F/M: 18/2) performed under acupuncture anaesthesia, supplemented by small doses of pethidine (mean: 45.0 mg, s.d. 8.9). Throughout surgery the patients remained conscious. During surgery a significant increase in the level of catecholamines and the above-mentioned circulating hormones and a decrease of immunoglobulins were observed, whereas the leucocyte and differential counts demonstrated leucocytosis due to lymphocytosis, a decreased percentage of eosinophils and a remarkably reduced percentage of neutrophils. In the postoperative phase, levels of noradrenaline and beta-endorphin remained elevated, whereas the other circulating hormones gradually returned to normal values. Immunoglobulin levels and eosinophil counts returned to the preinduction values within 24 h, and those of neutrophil and lymphocyte counts within 2 days. Changes in number of monocytes and basophils could not be detected peri- and postoperatively.