RESUMEN
The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and ß-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.
Asunto(s)
Hormona Adrenocorticotrópica/farmacología , Hormona del Crecimiento/farmacología , Adenohipófisis/metabolismo , Prolactina/farmacología , Timocitos/efectos de los fármacos , Tirotropina/farmacología , betaendorfina/farmacología , Hormona Adrenocorticotrópica/genética , Hormona Adrenocorticotrópica/inmunología , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación de la Expresión Génica , Hormona del Crecimiento/genética , Hormona del Crecimiento/inmunología , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Cultivo Primario de Células , Prolactina/genética , Prolactina/inmunología , Transducción de Señal , Timocitos/citología , Timocitos/inmunología , Tirotropina/genética , Tirotropina/inmunología , betaendorfina/genética , betaendorfina/inmunologíaRESUMEN
AIM: To compare immunochemical and clinical parameters in patients with chronic radicular and myofascial back pain. MATERIAL AND METHODS: A study included 92 patients (55 men and 37 women) with radicular pain syndrome and 97 patients (33 men and 64 women) with myofascial pain syndrome. Pain status was assessed with the differential visual analogous scale (at rest, on movement, at night and during spontaneous pain). Tensor algometry was used to measure pain intolerance thresholds at day and night. Levels of natural antibodies (nAB) to endogenous pain regulators (ß-endorphin, orphanin, serotonin, dopamine, histamine and angiotensin) were determined in the blood serum by ELISA. Patients were examined at admission to the hospital, on 10th and 21st days of treatment. RESULTS AND CONCLUSION: There was a significant decrease in pain syndrome in all patients to the 21st day. Pain intensity was higher in patients with radicular pain syndrome (Ñ<0.05) in all functional states. Pain intolerance thresholds were initially reduced in both groups. No significant between-group differences in the dynamics were not found either in men or women. Women had lower pain intolerance thresholds compared to men. An analysis of nAB profiles to pain regulators showed that they were correlated with higher and high indices, with the predominance of nAB to ß-endorphin, orphanin and histamine in both groups. The increased levels of antibodies circulate in the blood serum of patients with dorsalgia for a long time can further be a factor of pain chronification.
Asunto(s)
Dolor de Espalda/inmunología , Dolor de Espalda/fisiopatología , Síndromes del Dolor Miofascial/inmunología , Síndromes del Dolor Miofascial/fisiopatología , Percepción del Dolor , Radiculopatía/inmunología , Radiculopatía/fisiopatología , Adulto , Anticuerpos/sangre , Dolor de Espalda/sangre , Dopamina/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Histamina/inmunología , Humanos , Masculino , Persona de Mediana Edad , Síndromes del Dolor Miofascial/sangre , Dimensión del Dolor , Umbral del Dolor , Radiculopatía/sangre , Serotonina/inmunología , Factores Sexuales , Adulto Joven , betaendorfina/inmunologíaRESUMEN
INTRODUCTION: Testicular function in the sand rodent Psammomys obesus is subjected to seasonal alternations with a trigger of spermatogenesis in winter and a total quiescence which extends from late spring to summer. The aim of this study was to investigate the distribution of b-endorphin in the testis at the period of winter sexual activity and at its summer regression, and assess the effect of 17 ß-estradiol treatment on testicular morphology and b-endorphin expression. MATERIAL AND METHODS: The adult males were grouped into 4 groups (rest group, sexually active group, rest treated with 17ß-estradiol group and controls at sexual rest injected with olive oil, n = 5 in each group). Using anti-serum against b-endorphin, we studied its testicular expression by Western blot and cellular location by immunohistochemical (IHC) method, respectively. RESULTS: We detected by Western blot a peptide of 3.5 kDa molecular weight corresponding to b-endorphin only in sexually resting and control males. The 17ß-estradiol treatment induced a clear reduction in the b-endorphin band expression compared with the latter. These results were confirmed by the IHC analysis since b-endorphin was only observed in the testis at sexual rest and in controls, in majority of seminiferous tubules at the level of germ cells. The intensity of IHC labeling was significantly different between spermatogonia and spermatocytes I or round spermatids which revealed the strongest labeling. The intense immunoreactivity was also located in Leydig cells and highly significantly varied compared to the germ cells. The 17 ß-estradiol treatment decreased significantly the ß-endorphin signal in germ cells but not in Leydig cells. CONCLUSION: The 17ß-estradiol treatment induces a repressive effect on seasonal testicular endorphinergic system in P. obesus and this action targets exclusively the germ cells.
Asunto(s)
Estradiol/farmacología , Gerbillinae/metabolismo , Testículo/efectos de los fármacos , betaendorfina/biosíntesis , Animales , Células Germinativas/efectos de los fármacos , Células Germinativas/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Masculino , Aceite de Oliva/farmacología , Estaciones del Año , Túbulos Seminíferos/citología , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/metabolismo , Conducta Sexual/efectos de los fármacos , Espermatocitos/efectos de los fármacos , Espermatocitos/metabolismo , Espermatogénesis/efectos de los fármacos , Espermatogonias/efectos de los fármacos , Espermatogonias/metabolismo , Testículo/citología , Testículo/metabolismo , betaendorfina/química , betaendorfina/inmunologíaRESUMEN
Biomarker for prediction of development of low back pain, and disease progression in chronic conditions are virtually non-existent. In the present study, we examined evidence of inflammation in the peripheral blood and demonstrated significant changes in neuroinflammation markers in subjects with chronic low back pain in comparison with control subjects. The present study was performed using peripheral blood from subjects with chronic low back pain and age-matched control subjects. Western blotting, real-time RT-PCR, cell culture and in vitro assays were incorporated to perform the current study. We obtained evidence that the balance between proinflammatory and anti-inflammatory cytokines is misaligned, with decrease in interleukin-10 (IL-10) expression and increase in interleukin-6 (IL-6) expression. Furthermore, we demonstrated increase in CD16 monocyte expression. Cells were cultured under differential conditions to generate M1/M2 macrophages. In the macrophages, opioid secretory capacity was shown to be diminished. Finally, Dragon (repulsive guidance molecule b, RGMb) expression was shown diminished in M1 macrophages, which serves as a key transcriptional inhibitor of IL-6 expression. These biochemical and cellular alterations in chronic low back pain can serve as potential biomarkers for assessing disease initiation, intensity and progression.
Asunto(s)
Moléculas de Adhesión Celular Neuronal/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/diagnóstico , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Moléculas de Adhesión Celular Neuronal/inmunología , Diferenciación Celular , Enfermedad Crónica , Femenino , Humanos , Interleucina-10/inmunología , Interleucina-6/inmunología , Dolor de la Región Lumbar/genética , Dolor de la Región Lumbar/patología , Macrófagos/inmunología , Macrófagos/patología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/patología , Cultivo Primario de Células , Balance Th1 - Th2 , Transcripción Genética , betaendorfina/inmunología , betaendorfina/metabolismoRESUMEN
OBJECTIVE: Our aim was to study the possible markers of pain syndrome--indicators of pain sensitivity--pain pressure tolerance thresholds (PPTT), and immuno-indicators--natural antibodies against pain processing mediators (eAb) for evaluation the possibility of its using for a objective pain assessment at chronic low back pain. METHODS: Pain sensitivity was assessed daily and nightly, by measuring the PPTT The natural antibody levels (eAb), were determined in serum by ELISA. Measurement of all parameters were performed at 1st, 10th and 21 days. RESULTS: 173 patients (93 women and 80 men) with chronic low back pain were included in the study. At 1st day most patients had lowered PPTT: 55% of men and 74% during the day, 72% of men and 89% of women at night. Dynamic study has shown a tendency of PPTT normalization in men. The study of diurnal PPTT variations have shown that night PPTT lower than day PPTT on 15-17%. We found gender PPTT differences: PPTT values in women 17-26% lower than in men. Analysis of individual eAb profiles has showed that elevated and high levels of eAb to ß-endorphin, orphanin and histamine have 84%, 78%, 84% women and 82%, 85 and 95% men, respectively. These indicators higher than those for serotonin, dopamine and angiotensin (55%, 65%, 70% in women and 65%, 66%, 66% in men, respectively; p < 0.05). Dynamic study of eAb levels have shown a significant anti-histamine eAbs decrease (23%; p = 0.015) only. CONCLUSION: The pathological changes in pain sensitivity and levels of eAbs to pain-processing mediatos are evidenced. Further investigations are necessary to clarify to role of these variations in pain processing and for use these indicators for objective pain assessment.
Asunto(s)
Anticuerpos/sangre , Dolor de la Región Lumbar , Dimensión del Dolor/métodos , Umbral del Dolor , betaendorfina , Adulto , Femenino , Humanos , Inmunidad Humoral , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/inmunología , Dolor de la Región Lumbar/fisiopatología , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Percepción del Dolor , Reproducibilidad de los Resultados , Factores Sexuales , Factores de Tiempo , betaendorfina/sangre , betaendorfina/inmunologíaRESUMEN
OBJECTIVE: To observe the analgesic effect of electroacupuncture (EA) on collagen-induced arthritis (CIA) rats and its regulating effect on inflammation reaction and the endogenous opioid system of synovial tissues. Methods A total of 30 healthy male Wistar rats were randomly divided into a control group, a model group and an EA group, 10 rats in each one. The chronic pain model of CIA rats was made by cattle type-II collagen in the model group and EA group. Rats in the EA group were treated with EA at "Zusanli" (ST 36) and "Kunlun" (BL 60) for 30 min from 16th day after model establishment, once a day for consecutive 10 days. Rats in the control group did not receive any treatment. Rats in the model group were treated with fixation as the EA group. Threshold of pain, arthritis index, paw swelling were measured before model establishment and 16 d, 20 d, 23 d and 25 d after model establishment. The levels of beta-endorphin (ß-END), met-enkephalin (met-ENK), dynorphin A (Dyn A) were measured by radioimmunoassay; the mRNA expressions of mu opioid receptor (MOR), kappa opioid receptor (KOR) and delta opioid receptor (DOR) in synovial tissues of CIA rats were detected by I quantitative polymerase chain reaction (qPCR). RESULTS: Compared with the control group, threshold of pain was reduced (all P<0. 01), arthritis index was increased (all P<0. 01) and paw swelling was increased (all P<0. 01) in the model group on the 16th day, 20th day, 23rd day, 25th day after model establishment. Compared with the model group, the threshold of pain was increased in the EA group (all P<0. 01), arthritis index and paw swelling were reduced (all P<0. 01) on the 23rd day and 25th day after model establishment. Compared with the control group, the level of Dyn A in synovial tissues of CIA rats was increased in the model group (P<0. 01); the mRNA expressions of MOR, KOR and DOR were down-regulated lower than 0. 5 fold of normal level. Compared with the model group, the level of ß-END in synovial tissues of the knee joint was increased in the EA group (P<0. 05), and the mRNA expressions of MOR, KOR and DOR in synovial tissues of CIA rats were up-regulated more than 2 folds of normal level. CONCLUSION: The intervention of EA on chronic pain of CIA rats is superior, which is likely to be related with effects of EA on anti-inflammation and up-regulation of synovial tissue ß-END and MOR, KOR, DOR.
Asunto(s)
Analgésicos Opioides/inmunología , Artritis Reumatoide/terapia , Dolor Crónico/terapia , Electroacupuntura , Líquido Sinovial/inmunología , Analgesia por Acupuntura , Puntos de Acupuntura , Animales , Artritis Reumatoide/inmunología , Bovinos , Dolor Crónico/inmunología , Dinorfinas/genética , Dinorfinas/inmunología , Encefalina Metionina/genética , Encefalina Metionina/inmunología , Humanos , Masculino , Ratas , Ratas Wistar , Receptores Opioides mu/genética , Receptores Opioides mu/inmunología , betaendorfina/genética , betaendorfina/inmunologíaRESUMEN
Authors studied changes in the levels of antibodies to endogenous bioregulators (Ab) to Β-endorphin, orphanin, serotonin, dopamine and angiotensin in 36 healthy people and 109 patients with dorsopathy with chronic pain syndrome. The association of these immunological indicators with age and sex was found. It has been concluded that the levels of Ab to endogenous bioregulators may be considered as a marker of algic system pathology that does not depend on age and is sex-related.
Asunto(s)
Anticuerpos/sangre , Dolor Crónico/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Angiotensinas/inmunología , Anticuerpos/inmunología , Biomarcadores/sangre , Estudios de Casos y Controles , Dolor Crónico/sangre , Dopamina/inmunología , Femenino , Humanos , Vértebras Lumbares/patología , Masculino , Persona de Mediana Edad , Péptidos Opioides/inmunología , Serotonina/inmunología , Factores Sexuales , Enfermedades de la Médula Espinal/sangre , Enfermedades de la Médula Espinal/inmunología , betaendorfina/inmunología , NociceptinaRESUMEN
Traditional medical science has kept the mind separate from the body. Recently people realize the effect of mind on health and psychoneuroimmunology is the new evolved science that describes the interactions between psyche and soma. In this review through a typical psycho-neuro-endocrino-immune network the effects of psychological stress (acute, brief naturalistic and chronic) and relaxation on immune modulation has been shown. From this network Corticotrophin Releasing Factor (CRF), Adrenocorticotrophic Hormone (ACTH), Glucocorticoids (GC), alpha-endorphin and Met-enkephalin are found as important endocrine components and T cells, B cells, monocytes/macrophages, Natural Killer (NK) cells and their cytokines that is Tumor Necrosis Factor-alpha (TNF-alpha), Interferon Gamma (IFN-alpha) and interleukins such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12 etc. are found as important immune components. Finally, it has been shown that, acute, brief naturalistic and chronic stress have different immune modulatory activities which are harmful to one's homeostasis and relaxation can help to maintain that homeostasis.
Asunto(s)
Relajación/fisiología , Estrés Psicológico/inmunología , Hormona Liberadora de Corticotropina/inmunología , Encefalina Metionina/inmunología , Glucocorticoides/inmunología , Humanos , Modelos Inmunológicos , Modelos Neurológicos , Modelos Psicológicos , Neuroinmunomodulación/fisiología , Sistemas Neurosecretores/inmunología , betaendorfina/inmunologíaRESUMEN
Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of µ-opioid peptides, secreted by tumor cells, on anti-tumor immune responses. For this purpose, tumor growth was studied in wild-type and µ-opioid receptor-deficient (MOR-/-) mice injected with B16 melanoma cells. The ability of these cells to produce opioids was studied by Western blots in vitro. Finally, biopsy material from human melanomas was investigated by immunohistochemistry for ß endorphin expression. Injection of B16 melanoma cells, producing endogenous ß endorphin, in the flank of MOR-/- mice revealed a profound reduction in tumor growth, paralleled by a significantly higher infiltration of immune cells into the tumors, when compared to tumor growth after injection of B16 melanoma cells into wild-type mice. Opioids present in B16 cell supernatant significantly reduced the proliferation of normal but not MOR-/- leucocytes. Immunohistochemical analyses of biopsies from human melanoma tissues showed a positive correlation between expression of ß endorphin and tumor progression. Our data provide evidence that µ-opioid peptides may play a major role in cancer progression by modulating immune response. This finding may have implications for the future optimization of immunointerventions for cancer.
Asunto(s)
Melanoma/inmunología , Péptidos Opioides/inmunología , Neoplasias Cutáneas/inmunología , Animales , Progresión de la Enfermedad , Humanos , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Melanoma/metabolismo , Melanoma/patología , Melanoma Experimental/inmunología , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Noqueados , Péptidos Opioides/biosíntesis , Receptores Opioides mu/agonistas , Receptores Opioides mu/deficiencia , Receptores Opioides mu/genética , Receptores Opioides mu/inmunología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , betaendorfina/inmunología , betaendorfina/metabolismoRESUMEN
Endogenous opioid peptides represent the group of bioregulatory factors possessing a wide range of biologically active effects. One of most essential functions of endogenous opioids appears to be the realization of cellular interaction between nervous and immune systems. Beta-endorphin is a peptide hormone that is the most active and multi-functional representative of the opioid peptide family. This review summarizes current observations on the nature ofbeta-endorphin, its production by the immune system cells, opiate receptor structure and expression, as well as the peptide effect on the processes of cellular activation, proliferation, and differentiation in innate and adaptive immunity.
Asunto(s)
Inmunidad Adaptativa/fisiología , Inmunidad Innata/fisiología , Receptores Opioides/inmunología , betaendorfina/inmunología , Animales , Diferenciación Celular/inmunología , Proliferación Celular , Regulación de la Expresión Génica/inmunología , Humanos , Receptores Opioides/biosíntesis , betaendorfina/metabolismoRESUMEN
To pursue further the possible de novo biosynthetic pathway of endomorphins in rat brain we raised antibodies to endomorphin-2 conjugate in rabbits. Antiserum R1 recognized endomorphin-2 with good selectivity as compared to endomorphin-1 with a median detection value of 65.5+/-7.5 pg/tube (n=7), whereas R4 antiserum recognized both endomorphins with similar sensitivity. Neither antisera recognized YP-related di- or tripeptides or YGGF-related opioid sequences (enkephalins, beta-endorphin, dynorphin). Using the same rat brain extraction-RP-HPLC-gradient separation paradigm as previously, antisera detected 144.6+/-40.0 (n=3) pg/g wet brain weight endomorphin-2-like immunoreactivity in the fraction corresponding to standard endomorphin-2 retention time and also in the fraction matching endomorphin-2-OH standard retention time (179.1+/-30.1 pg/g). Since R1 failed to recognize authentic endomorphin-2-OH, the second immunoreactive species must be different from both endomorphin-2 and endomorphin-2-OH. Possible biosynthetic intermediates to endomorphins, synthetic YPFFG and YPWFG had retention times close to the parent endomorphin standards in RP-HPLC gradient separation profile. The former was a mu-opioid receptor agonist of medium potency in the in vitro assays (rat brain RBA>P gamma S binding and mouse vas deferens), whereas the latter was a weak mu-opioid receptor agonist with a significant delta-opioid receptorial action as well and a definite indication of partial agonism.
Asunto(s)
Encéfalo/inmunología , Oligopéptidos/inmunología , Péptidos/inmunología , Secuencia de Aminoácidos , Animales , Cromatografía Líquida de Alta Presión , Dinorfinas/inmunología , Encefalinas/inmunología , Sueros Inmunes/inmunología , Masculino , Ratones , Antagonistas de Narcóticos/inmunología , Péptidos/aislamiento & purificación , Conejos , Radioinmunoensayo/métodos , Ratas , Ratas Wistar , betaendorfina/inmunologíaRESUMEN
BACKGROUND: The primary aim of the study was to confirm the increase of plasmatic IR beta-endorphin material during the perioperative period in children. The second was to search for the factors responsible for this increment. METHODS: Seventy-two consecutive children undergoing a surgical procedure were recruited. Pre-anaesthesia and anaesthesia were standardised. Plasmatic IR beta-endorphin material was measured at three timepoints: at baseline (t (0)), before induction (t (1)), and at the end of anaesthesia (t (2)). Two general linear models were set up to analyse the influence of demographics and clinics on the IR beta-endorphin variation between t (0) and t (1). A third model was established to process the possible surgical factors contributing to the IR beta-endorphin variation between t (1) and t (2). RESULTS: ANOVA showed that IR beta-endorphin concentrations increased significantly across the three timepoints (p < 0.0001). Wilcoxon test proved that the difference was significant both for t (0) vs. t (1) and for t (1) vs. t (2). None of the factors taken into account in the pre-operative period influenced the increase in IR beta-endorphin between t (0) and t (1). Of the factors taken into account in the surgical period, only the type of procedure was significant (p = 0.005). The t-test showed that IR beta-endorphin significantly increased during spermatic and epigastric anastomosis (p = 0.000), orchidopexy (p = 0.02), Van der Meulen urethroplasty (p = 0.004), and Duckett urethroplasty (p = 0.003). CONCLUSION: Plasmatic beta-endorphin increases during the perioperative period in children. The site of surgery is responsible for this increment during intervention.
Asunto(s)
Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Atención Perioperativa/estadística & datos numéricos , Estrés Fisiológico/inmunología , betaendorfina/sangre , betaendorfina/inmunología , Adaptación Fisiológica/inmunología , Adolescente , Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Análisis de Varianza , Niño , Preescolar , Femenino , Humanos , Modelos Lineales , Masculino , Factores de TiempoRESUMEN
Atopic dermatitis (AD) is a disease of increasing incidence among paediatric patients. Among the factors involved in its pathogenesis is the alteration of the immune response, and so the objective of this study was to evaluate the involvement of certain neuroendocrine factors with immune properties in the development of the disease. Fifty-five subjects were selected and divided into the following three groups: healthy subjects, those diagnosed with symptomatic AD and those with asymptomatic AD. Plasma levels of melatonin and beta-endorphins were measured by radioimmunoassay, in serum samples obtained at 9 am and 9 pm, with two samples being obtained from each of the patients and controls. In the phases of AD outbreaks, there is a reduction in the serum levels of both melatonin and beta-endorphin. In the case of melatonin, the difference is statistically significant only during the day, although nocturnal levels are greater for both hormones. In AD, a central neuroendocrine dysfunction may be a primary pathogenic event. Our hypothesis is that the physiological nocturnal peak of melatonin due to pineal gland production may mask the decline of melatonin of possibly extrapineal (immunological) origin during episodes of dermatitis outbreaks. Further studies are required, particularly of neurovegetative and hormonal aspects, to better define this process. Such a definition would also be of therapeutic interest.
Asunto(s)
Ritmo Circadiano , Dermatitis Atópica/inmunología , Melatonina/sangre , Sistemas Neurosecretores/inmunología , betaendorfina/sangre , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Melatonina/inmunología , Persona de Mediana Edad , Glándula Pineal/metabolismo , betaendorfina/inmunologíaRESUMEN
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.
Asunto(s)
Analgesia por Acupuntura , Analgesia , Hidrocortisona/sangre , betaendorfina/sangre , Adulto , Electroacupuntura , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , betaendorfina/inmunologíaRESUMEN
Endogenous opioids released from leukocytes extravasating into injured tissue can interact with peripheral opioid receptors to inhibit nociception. Animal studies have shown that the homing of opioid-producing leukocytes to the injured site is modulated by spinal blockade of noxious input. This study investigated whether epidural analgesia (EDA) influences the migration of beta-endorphin (END) and/or met-enkephalin (ENK)-containing leukocytes into the subcutaneous wound tissue of patients undergoing abdominal surgery. In part I patients received general anesthesia combined either with intra- and postoperative EDA (with bupivacaine and fentanyl) or with postoperative patient controlled intravenous analgesia (PCIA; with the opioid piritramide). In part II patients received general anesthesia combined with either epidural fentanyl or bupivacaine which was continued postoperatively. Samples of cutanous and subcutanous tissue were taken from the wound site at the beginning, at the end and at various times after surgery, and were examined by immunohistochemistry for the presence of END and ENK. We found that (i) epidural bupivacaine, fentanyl and PCIA provided similar and clinically acceptable postoperative pain relief; (ii) compared to PCIA, epidural bupivacaine or fentanyl did not change the gross inflammatory reaction within the surgical wound; (iii) opioid-containing leukocytes were almost absent in normal subcutaneous tissue but migrated to the inflamed wound tissue in ascending numbers within a few hours, reaching a peak at about 24 h after surgery; (iv) compared to PCIA, EDA resulted in significantly decreased homing of END-containing leukocytes to the injured site at 24 h after surgery; and (v) the magnitude of this decrease was similar regardless of the epidural medication. These findings suggest that nociceptive but not sympathetic neurons are primarily involved in the attraction of opioid-containing leukocytes during early stages of inflammation.
Asunto(s)
Analgésicos Opioides/inmunología , Movimiento Celular/efectos de los fármacos , Encefalina Metionina/metabolismo , Leucocitos/efectos de los fármacos , Cicatrización de Heridas/inmunología , betaendorfina/metabolismo , Adyuvantes Anestésicos/inmunología , Adyuvantes Anestésicos/farmacología , Anciano , Analgesia Controlada por el Paciente , Analgésicos Opioides/uso terapéutico , Anestesia Epidural , Anestésicos Locales/inmunología , Anestésicos Locales/uso terapéutico , Bupivacaína/inmunología , Bupivacaína/uso terapéutico , Movimiento Celular/inmunología , Encefalina Metionina/efectos de los fármacos , Encefalina Metionina/inmunología , Femenino , Fentanilo/inmunología , Fentanilo/uso terapéutico , Humanos , Leucocitos/inmunología , Leucocitos/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Nociceptores/efectos de los fármacos , Nociceptores/inmunología , Dolor Postoperatorio/inmunología , Dolor Postoperatorio/prevención & control , Pirinitramida/uso terapéutico , Tejido Subcutáneo/inmunología , Fibras Simpáticas Posganglionares/efectos de los fármacos , Fibras Simpáticas Posganglionares/inmunología , Cicatrización de Heridas/efectos de los fármacos , betaendorfina/efectos de los fármacos , betaendorfina/inmunologíaRESUMEN
Beta-endorphin radioimmunoassays (RIAs) are widely performed following physical, emotional and environmental challenges in the rat. In the literature, a wide range of techniques have been described, but in the present study, we have focused on methodological aspects of beta-endorphin RIAs, investigating various characteristics of human and rat specific antibodies. Initial studies verified that the RIA outcome was not appropriate when using non-species compatible components. Novel rat beta-endorphin antibodies, r 4114 and r 4268, were raised in rabbits and characterised in terms of specificity, avidity and titer. Both of the new antisera showed 68.1% cross-reactivity with human beta-endorphin. The ED50 was 50+/-8 pmol/l, and the mean ED80 was 17 pmol/l for r 4268 but three-fold higher for r 4114. The intra-assay coefficient of variation (CV) was 7% at 100 pmol/l and the inter-assay CV was 10% at the same level for r 4268 and similar for r 4114. Using this novel rat beta-endorphin RIA for analyses of diurnal influence and removal from the Animal House cage, no significant changes were observed in either the hypothalamus or peri-aqueductal grey regions. These results suggest that rat beta-endorphin concentrations in these brain areas are not affected by order of removal or diurnal variation.
Asunto(s)
Anticuerpos/inmunología , Ritmo Circadiano , Hipotálamo/química , Radioinmunoensayo/métodos , betaendorfina/análisis , Secuencia de Aminoácidos , Animales , Reacciones Cruzadas , Humanos , Masculino , Datos de Secuencia Molecular , Ratas , Ratas Endogámicas Lew , Estrés Psicológico/metabolismo , betaendorfina/inmunologíaRESUMEN
OBJECTIVE: To observe the effects and mechanisms of beta-endorphin (beta-END) preventing collagen induced arthritis (CIA) by neuroimmuno-regulating pathway. METHODS: Female wistar (Ws) rats were used in this study. CIA was induced by Native bovine type II collagen emulsified with complete Freund's adjuvant (CFA). Beta-END was administered i.p. to CIA rats every other day from the 14th day (secondary immunization) to the 35th day after primary immunization. Clinical assessments were performed by two independent, blinded examiners every other day. Pathological and radiological observations were taken on the 35th day after the primary immunization. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), regulated upon activation, normal T-cell expressed and secreted (RANTES), inducible NO syntheses (iNOS), matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA expression of synovium tissues of CIA rats was estimated by quantitative RT-PCR. The frequency of spleen Th1 and Th2 cells were assessed by fluorescence activated cell sorter (FACS) assay. RESULTS: Clinical manifestation of rats with CIA were significantly abrogated or ameliorated by treatment with beta-END. Beta-END treatment in vivo could down-regulate mRNA expression of several pro-inflammatory cytokines, chemokines and MMPs in CIA synovial, and polarize Th1/Th2 balance to Th2. CONCLUSION: Beta-END alleviates CIA through both depressing Th1 responses and down-regulating proinflammatory and other rheumatic factors, suggesting beta-END is a promising anti-inflammatory and anti-rheumatic agent in treating CIA.
Asunto(s)
Artritis Experimental/inmunología , Artritis Experimental/prevención & control , Artritis Reumatoide/inmunología , Artritis Reumatoide/prevención & control , Citocinas/metabolismo , betaendorfina/inmunología , Análisis de Varianza , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/enzimología , Artritis Reumatoide/enzimología , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Colágeno , Citocinas/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Recuento de Linfocitos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Neuroinmunomodulación/inmunología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , ARN Mensajero/análisis , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Método Simple Ciego , Bazo/citología , Bazo/inmunología , Células TH1/citología , Células Th2/citología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Intrathecal (i.t.) pretreatment with a low dose (0.3 nmol) of morphine causes an attenuation of i.t. morphine-produced analgesia; the phenomenon has been defined as morphine-induced antianalgesia. The opioid-produced analgesia was measured with the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with low dose (0.3 nmol) of morphine time dependently attenuated i.t. morphine-produced (3.0 nmol) TF inhibition and reached a maximal effect at 45 min. Intrathecal pretreatment with morphine (0.009-0.3 nmol) for 45 min also dose dependently attenuated morphine-produced TF inhibition. The i.t. morphine-induced antianalgesia was dose dependently blocked by the nonselective mu-opioid receptor antagonist (-)-naloxone and by its nonopioid enantiomer (+)-naloxone, but not by endomorphin-2-sensitive mu-opioid receptor antagonist 3-methoxynaltrexone. Blockade of delta-opioid receptors, kappa-opioid receptors, and N-methyl-D-aspartate (NMDA) receptors by i.t. pretreatment with naltrindole, nor-binaltorphimine, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), respectively, did not affect the i.t. morphine-induced antianalgesia. Intrathecal pretreatment with antiserum against dynorphin A(1-17), [Leu]-enkephalin, [Met]-enkephalin, beta-endorphin, cholecystokinin, or substance P also did not affect the i.t. morphine-induced antianalgesia. The i.t. morphine pretreatment also attenuated the TF inhibition produced by opioid muagonist [D-Ala2, N-Me-Phe4,Gly-ol5]-enkephalin, delta-agonist deltorphin II, and kappa-agonist U50,488H. It is concluded that low doses (0.009-0.3 nmol) of morphine given i.t. activate an antianalgesic system to attenuate opioid mu-, delta-, and kappa-agonist-produced analgesia. The morphine-induced antianalgesia is not mediated by the stimulation of opioid mu-, delta-, or kappa-receptors or NMDA receptors. Neuropeptides such as dynorphin A(1-17), [Leu]-enkephalin, [Met]-enkephalin, beta-endorphin, cholecystokinin, and substance P are not involved in this low-dose morphine-induced antianalgesia.
Asunto(s)
Analgesia , Morfina/administración & dosificación , Naltrexona/análogos & derivados , Dolor/tratamiento farmacológico , Médula Espinal/efectos de los fármacos , Animales , Maleato de Dizocilpina/farmacología , Interacciones Farmacológicas , Tolerancia a Medicamentos , Dinorfinas/inmunología , Dinorfinas/metabolismo , Encefalinas/inmunología , Encefalinas/metabolismo , Masculino , Ratones , Morfina/uso terapéutico , Naloxona/farmacología , Naltrexona/farmacología , Oligopéptidos/metabolismo , Dimensión del Dolor/efectos de los fármacos , Receptores Opioides delta/agonistas , Receptores Opioides kappa/agonistas , Receptores Opioides mu/agonistas , Sustancia P/inmunología , Sustancia P/metabolismo , betaendorfina/inmunología , betaendorfina/metabolismoRESUMEN
Psychological, endocrine and immune parameters were measured over a 6-month period in 14 healthy subjects who underwent an unpredictable acute emotional stress (e.g. sudden death of a loved one) compared with 14 controls who did not. Probands were profoundly stressed as assessed 10 days after bereavement by their scores on the Hamilton Rating Scales of Anxiety and Depression, adrenocorticotropin and cortisol plasma concentrations, and non-suppression in response to dexamethasone. Functional alterations of immune parameters, such as responsiveness of peripheral blood lymphocytes to mitogens, were found 40 days after bereavement. Despite a normal number of circulating lymphocyte subsets, the functional activity of natural killer (NK) cells was markedly reduced at day 40. Changes in the intracellular concentration of beta-endorphin in peripheral blood mononuclear cells correlated with anxiety and depression scores. Controls showed no changes in psychometric, endocrine and immune measures during the 6-month study. Cluster analysis revealed two groups of bereaved subjects with different patterns of immune and endocrine changes: (1) Five subjects, characterized by harm-avoidant temperament and long-lasting dysphoric mood, showed reduced responsiveness of peripheral blood lymphocytes to mitogens, decreased NK cell activity and non-suppression in response to dexamethasone that persisted for 6 months. (2) Nine subjects showed significant changes only during the early phase after bereavement. Our data suggest that the immunological consequences of stress do not simply overlap with psychological and endocrine alterations, and are particularly severe and long-lasting in a subgroup of subjects, indicating the importance of individual variability in the capacity to cope with stress.