beta-endorphin and Arthritis--Rheumatoid

Proopiomelanocortin (POMC)-derived peptides such as melanocortins and β-endorphin (β-ED) exert their pleiotropic effects via binding to melanocortin receptors (MCR) and opioid receptors (OR). There is now compelling evidence for the existence of a functional POMC system within the osteoarticular system. Accordingly, distinct cell types of the synovial tissue and bone have been identified to generate POMC-derived peptides like β-ED, ACTH, or α-MSH. MCR subtypes, especially MC1R, MC2R (the ACTH receptor), MC3R, and MC4R, but also the μ-OR and δ-OR, have been detected in various cells of the synovium, cartilage, and bone. The respective ligands of these POMC-derived peptide receptors mediate an increasing number of newly recognized biological effects in the osteoarticular system. These include bone mineralization and longitudinal growth, cell proliferation and differentiation, extracellular matrix synthesis, osteoprotection, and immunomodulation. Importantly, bone formation is also regulated by the central melanocortin system via a complex hormonal interplay with other organs and tissues involved in energy metabolism. Among the POMC-derived peptides examined in cell culture systems from osteoarticular tissue and in animal models of experimentally induced arthritis, α-MSH, ACTH, and MC3R-specific agonists appear to have the most promising antiinflammatory actions. The effects of these melanocortin peptides may be exploited in future for the treatment of patients with inflammatory and degenerative joint diseases.

Topics: Animals; Arthritis, Rheumatoid; beta-Endorphin; Bone and Bones; Cartilage; Humans; Joints; Melanocortins; Osteoarthritis; Pro-Opiomelanocortin; Signal Transduction

This study aimed at evaluating the effects of a dynamic physical training programme on circulating levels of corticotropin-releasing hormone (CRH), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EP) after high-intensity training for 6 weeks (60 min twice a week) and after low-intensity training (home-training) for another 6 months in patients with rheumatoid arthritis (RA) and in healthy subjects. Additionally, differences in neuropeptide levels between the two groups were studied. A total of 30 patients with RA were randomly allocated to the study, 15 in the training group (TG) and 15 in the control group (CG). In addition, 20 healthy subjects (10 in TG; 10 in CG) participated. In addition to the biochemical analyses, the following variables were assessed for the RA group: pain and disability (Stanford health assessment questionnaire), joint tenderness (Ritchie articular index), disease activity, muscle function, aerobic capacity, sociodemographic data and attitudes. The results obtained at the start revealed significant differences (p < 0.05) between RA patients and healthy subjects concerning CRH levels, RA patients showing the lower levels (RA-group Md = 24 pmol/L, healthy group Md = 29 pmol/L). No significant differences concerning beta-LPH and beta-EP were found here. After the high-intensity training period, a significant increase of the CRH levels were found for the RA-TG (pretest Md = 24 pmol/L, after 6 weeks Md = 27 pmol/L, p < 0.05). No such results were found for the healthy-TG or the control groups. Concerning beta-EP, significant differences between the RA-TG and healthy-TG were found after the training. RA patients generally showing higher levels as compared with the healthy (RA-group Md = 42 pmol/L, healthy group Md = 36 pmol/L, p < 0.05). The same pattern was found for the beta-LPH levels. In conclusion, the effects of physical training on circulating neuropeptides remain still incompletely examined, and there is no definite answer to the question whether increased beta-EP levels are good or bad.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; beta-Lipotropin; Corticotropin-Releasing Hormone; Female; Humans; Male; Middle Aged; Neuropeptides; Pain; Physical Education and Training

This study was designed to examine the effects of aspirin, naloxone and placebo treatment on serum beta-endorphin concentration and joint pain in patients with rheumatoid arthritis (RA). Ten patients with definite or classical RA were studied. All treatments were administered in a randomized sequence. On each study day, the following measurements were carried out at specified time intervals: serum beta-endorphin concentration, serum salicylate concentration and joint pain score on a visual analogue horizontal scale. We conclude that in patients with rheumatoid arthritis suffering from chronic joint pain, serum beta-endorphin does not appear to play a role in pain relief.

Topics: Arthritis, Rheumatoid; Aspirin; beta-Endorphin; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Humans; Naloxone; Pain; Pain Measurement; Placebos; Random Allocation

Co-encapsulation of drugs provides a convenient means for treating different symptoms of a disease. Celastrol (Cel) shows potent anti-arthritic activity and Indomethacin (Indo) is effective in relieving inflammatory pain. Nanostructured lipid carriers loaded with Celastrol and Indomethacin (Cel-Indo-NLCs) were prepared by emulsification evaporation-solidification method, optimized by the Box-Behnken design and characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and powder X-ray diffraction analysis (PXRD). Visualization of transdermal translocation of Cel-Indo-NLCs was achieved by confocal laser scanning microscope (CLSM). Further, Cel-Indo-NLCs were incorporated into Carbopol 940 for transdermal delivery. The in vitro studies were evaluated by using the Franz diffusion cells. Cel-Indo-NLCs depicted small particle size (26.92 ± 0.62 nm) and PDI (0.201 ± 0.01), high entrapment efficiency (96.56 ± 1.41%) and drug load (3.65 ± 0.05%). Moreover, Cel-Indo-NLCs showed prominent effect of decreasing paw oedema, inhibiting inflammation and pain by regulating the levels of IL-1β, TNF-α, β-endorphin and Substance P. After the administration of Cel-Indo-NLCs-gel, no skin irritation was observed in rats. There was no difference of gastrointestinal tract between different groups of rats when they were sacrificed. The histological analysis showed no renal and reproductive toxicity. Therefore, it can be concluded that co-encapsulation strategy based NLCs have the potential to provide safe transdermal delivery and are promising in treatment of pain and inflammation associated with rheumatoid arthritis.

Topics: Administration, Cutaneous; Animals; Arthritis, Rheumatoid; beta-Endorphin; Drug Carriers; Drug Liberation; Indomethacin; Interleukin-1beta; Pentacyclic Triterpenes; Rats; Rats, Sprague-Dawley; Skin Absorption; Substance P; Triterpenes; Tumor Necrosis Factor-alpha

To observe the analgesic effect of acupuncture and to explore its central analgesic mechanism in rheumatoid arthritis rabbits.
 Methods: A total of 60 flap-eared white rabbits were randomly assigned into a normal control group (n=6), a model group (n=6), a body-acupuncture group (n=24), and a buccal acupuncture group (n=24). The later 2 groups were further randomly assigned into 0, 0.5, 1, and 2 h subgroups, with 6 cases in each group. The rheumatoid arthritis model was established by induction of egg-albumin. In the body acupuncture group, bilateral "Xiyan" and "Zusanli" were punctured for 15 s while in the buccal acupuncture group, acupuncture was applied to "Xi" for 15 s, with the needle retaining for 30 min. The pain threshold was detected with PL-200, taking struggle movements of rabbits as a measurement index, response latency from irradiation to struggling movements as the rabbit's pain threshold. The contents of β-endorplhin (β-EP) and cholecystokinin-8 (CCK-8) in cerebrospinal fluid were examined by radioimmunoassay.
 Results: Compared with the control group, pain threshold and CCK-8 levels decreased significantly (P<0.01) and the concentration of β-EP significantly increased (P<0.05) in the model group. The pain threshold in the body-acupuncture group and the buccal acupuncture group at 0 and 
1 h (P<0.05 or P<0.01) increased significantly, while the β-EP and CCK-8 contents in the body-acupuncture group and the buccal acupuncture group were significantly higher than those in the model group (P<0.01 or P<0.05). Both β-EP and CCK-8 contents in the buccal acupuncture group at 0 h were significantly higher than those in the body-acupuncture group (P<0.05).
 Conclusion: The analgesic effect of buccal acupuncture is superior to that of body-acupuncture. Both buccal acupuncture and body-acupuncture can effectively raise the pain threshold in acute arthritis rabbits, which is closely associated with their effects in the up-regulation of β-EP and CCK-8 contents in cerebrospinal fluid.. 目的：探究针刺对患有类风湿性关节炎大耳白兔的镇痛时效及其中枢作用机制。方法：将60只大耳白兔随机分为正常组(n=6)、模型组(n=6)、体针组(n=24)和颊针组(n=24)，再将后两组分为针后即时(0 h)、针后0.5，1，2 h 4个亚组，每组各6只。白兔类风湿性关节炎模型采用卵蛋白诱导建立。体针组针刺双侧“膝眼”和“足三里”
1次，颊针组双侧颊针针刺“膝”1次，行针15 s，留针30 min。采用PL-200热刺痛仪检测痛阈，以兔出现缩耳挣扎动作为疼痛反应指标，自照射开始至兔出现反应的潜伏期时间作为该兔的痛阈值；使用放射免疫法检测兔脑脊液中β-内啡肽(β-endorplhin，β-EP)及八肽胆囊收缩素(cholecystokinin-8，CCK-8)含量。结果：与正常组相比，模型组痛阈和CCK-8含量显著降低(P<0.01)，β-EP含量显著升高(P<0.05)；与模型组相比，体针组和颊针组的痛阈在0和1 h(P<0.05或P<0.01)显著升高；体针组和颊针组兔脑脊液中CCK-8和β-EP含量均显著高于模型组(P<0.01或P<0.05)；颊针组的即时(0 h)CCK-8和β-EP含量显著高于体针组(P<0.05)，其他时间无明显变化。结论：针刺治疗可以有效缓解类风湿性关节炎的疼痛，颊针疗法的即时镇痛效应优于体针治疗，且这种即时镇痛效应与脑脊液中β-EP和CCK-8含量变化相关。.

Topics: Acupuncture Analgesia; Acupuncture Points; Animals; Arthritis, Rheumatoid; beta-Endorphin; Mouth; Movement; Pain Threshold; Rabbits; Random Allocation; Sincalide; Time Factors

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 (β-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).. 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 β-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.. 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 β-END and MOR, KOR, DOR.

Topics: Acupuncture Analgesia; Acupuncture Points; Analgesics, Opioid; Animals; Arthritis, Rheumatoid; beta-Endorphin; Cattle; Chronic Pain; Dynorphins; Electroacupuncture; Enkephalin, Methionine; Humans; Male; Rats; Rats, Wistar; Receptors, Opioid, mu; Synovial Fluid

To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin (POMC) and prodynorphin (PDYN) mRNA expressions and plasma beta-endorphin (beta-EP) content in rheumatoid arthritis (RA) rats, to understand the mechanism of moxibustion analgesia and its dose-effect relationship.. Twelve male Wistar rats were randomly selected from 48 male Wistar rats as a normal control group. The RA model was created by raising rats in a windy (blowing with electric fan), cold (6 degrees C +/- 2 degrees C), and wet (80%-90% humidity) environment for 20 days, 12 h each day. This was followed by injection of Freund's complete adjuvant (0.15 mL) into the ankle. Then, rats were randomly divided into a model group, moxibustion group I, and moxibustion group II, with 12 rats in each group. In moxibustion groups I and II, moxibustion was given at Shenshu (BL 23) and Zusanli (ST 36) for 20 and 40 min, respectively, once daily for 15 days. Hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content were determined.. Compared with the normal group, the pressure pain threshold decreased, while the hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content increased in the moxibustion groups (P < 0.01). Compared with the model group, the pressure pain threshold, hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in the moxibustion groups increased significantly (P < 0.01). Compared the moxibustion group I, the pain threshold, hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in moxibustion group II significantly increased (P < 0.01).. Moxibustion has an analgesic effect and increases hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in RA rats.The analgesic effect in moxibustion group II is betterthan that in moxibustion group I.

Topics: Acupuncture Points; Analgesia; Animals; Arthralgia; Arthritis, Rheumatoid; beta-Endorphin; Disease Models, Animal; Enkephalins; Humans; Hypothalamus; Male; Moxibustion; Pain Threshold; Pro-Opiomelanocortin; Protein Precursors; Rats; Rats, Wistar

The goal of this study is to determine and compare the β-endorphin levels in the synovial fluid of patients with different joint disorders (avascular necrosis, AVN; osteoarthritis, OA; and rheumatoid arthritis, RA of the hip or knee). Eighty-seven patients were involved in our study with an average age of 62 years. Thirty-three patients had AVN (18 hips, 15 knees). Twenty-three patients were diagnosed with OA (14 hips, 9 knees), and 31 patients suffered from RA (12 hips, 19 knees). We measured the β-endorphin levels of the synovial fluids -harvested from surgery-with radioimmunoassay. No significant difference was found in the β-endorphin levels of the synovial fluid from AVN comparing to OA and RA, however β-endorphin level was significantly higher in RA group than among patients with OA (p = 0.01). Synovial β-endorphin level was slightly lower in knee comparing to hip joint p = (0.06). When examining the different joints separately in compliance with diagnoses, we concluded that the synovial β-endorphin level from AVN was between the values of OA and RA without significant difference, whereas it was significantly higher in the knee of RA, than of OA groups (p = 0.05 knee, p = 0.2 hip). Our results confirmed those experiments which stated that there is a significant increase in synovial β-endorphin level in patients with inflammatory autoimmune diseases (e.g., RA), comparing to the level measured in degenerative conditions (e.g., OA).

Topics: Aged; Arthritis, Rheumatoid; beta-Endorphin; Female; Femur Head; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Osteonecrosis; Pilot Projects; Synovial Fluid

Intra-articularly applied opioid agonists or antagonists modulate pain after knee surgery and in chronic arthritis. Therefore, the expression of beta-endorphin (END), Met-enkephalin (ENK), and mu and delta opioid receptors (ORs) within synovium of patients with joint trauma (JT), osteoarthritis (OA) and rheumatoid arthritis (RA) were examined.. Synovial samples were subjected to double immunohistochemical analysis of opioid peptides with immune cell markers, and of ORs with the neuronal markers calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH).. END and ENK were expressed by macrophage-like (CD68(+)) and fibroblast-like (CD68(-)) cells within synovial lining layers of all disorders. In the sublining layers, END and ENK were mostly expressed by granulocytes in patients with JT, and by macrophages/monocytes, lymphocytes and plasma cells in those with OA and RA. Overall, END- and ENK-immunoreactive (IR) cells were more abundant in patients with RA than in those with OA and JT. ORs were found on nerve fibres and immune cells in all patients. OR-IR nerve fibres were significantly more abundant in patients with RA than in those with OA and JT. muORs and deltaORs were coexpressed with CGRP but not with TH.. Parallel to the severity of inflammation, END and ENK in immune cells and their receptors on sensory nerve terminals are more abundant in patients with RA than in those with JT and OA. These findings are consistent with the notion that, with prolonged and enhanced inflammation, the immune and peripheral nervous systems upregulate sensory nerves expressing ORs and their ligands to counterbalance pain and inflammation.

Topics: Adult; Aged; Aged, 80 and over; Arthritis; Arthritis, Rheumatoid; beta-Endorphin; Biomarkers; Enkephalin, Methionine; Female; Humans; Immunohistochemistry; Joints; Leukocytes; Male; Middle Aged; Osteoarthritis; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu; Synovial Membrane

To observe the effects and mechanisms of beta-endorphin (beta-END) preventing collagen induced arthritis (CIA) by neuroimmuno-regulating pathway.. 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.. 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.. 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.

Topics: Analysis of Variance; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; beta-Endorphin; Chemokine CCL5; Collagen; Cytokines; Disease Models, Animal; Down-Regulation; Female; Interleukin-1; Interleukin-6; Lymphocyte Count; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neuroimmunomodulation; Nitric Oxide Synthase Type II; Rats; Rats, Wistar; RNA, Messenger; Severity of Illness Index; Single-Blind Method; Spleen; Th1 Cells; Th2 Cells; Tumor Necrosis Factor-alpha

To determine whether endorphin (END) and enkephalin (ENK) modulate excessive synovial cell functions in patients with rheumatoid arthritis (RA).. Effects of leucine-enkephalin (leu-ENK), methionine-enkephalin (met-ENK), and beta-endorphin (END) on proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells were analyzed by immunoblotting, and their mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilution of complementary DNA. Expression of opioid receptors on RA synovial cells was assessed by immunohistochemical staining, radioreceptor assay, and RT-PCR.. Leu-ENK, met-ENK, and END inhibited tumor necrosis factor-alpha and interleukin 1beta production at the level of mRNA expression. ENK and END inhibited MMP-9 production and its enzymatic activity by RA synovial cells. The mu-subtype opioid receptor was expressed in the RA synovial lining and sublining cells. Radioreceptor assay suggested expression of high affinity receptor for END on RA synovial cells. The mu-subtype opioid receptor-specific antagonist, naloxone, reversed the inhibitory effect of the opioid peptides. The opioid peptides inhibited nuclear translocation and phosphorylation of the transcription factor, cyclic AMP responsive element binding protein (CREB) in RA synovial cells.. Leu-ENK, met-ENK, and END inhibited excessive RA synovial cell functions in vitro. The opioid hormones may have not only antinociceptive action, but also antiinflammatory effects on synovitis itself in RA.

Topics: Aged; Arthritis, Rheumatoid; beta-Endorphin; Cell Division; Cell Nucleus; Cells, Cultured; Cyclic AMP Response Element-Binding Protein; Enkephalin, Leucine; Enkephalin, Methionine; Female; Gene Expression; Humans; Interleukin-1; Male; Matrix Metalloproteinase 9; Middle Aged; Neuroimmunomodulation; Opioid Peptides; Receptors, Opioid; Synovial Membrane; Synovitis; Tumor Necrosis Factor-alpha

Topics: Acupuncture Therapy; Adrenocorticotropic Hormone; Arthritis, Rheumatoid; beta-Endorphin; Electric Stimulation Therapy; Humans; Osteoarthritis; Transcutaneous Electric Nerve Stimulation

Beta-endorphin is a neuroendocrine peptide, with morphine-like effects, produced by anterior pituitary, cells of the immune system, and synovial cells. The clinical significance of Plasma Beta-endorphin was investigated in a well characterized cohort of 20 RA patients and 10 healthy controls. Beta-endorphin extraction and concentration were carried out according to Wardlaw. Plasma Beta-endorphin assay was measured as described by Naber. Plasma Beta-endorphin levels in severe RA patients were significantly lower (16.1 +/- 6.2 pg/ml) than in mild RA patients (45.4 +/- 2.8 pg/ml), P < 0.0001. The mean serum levels of Beta-endorphin were also significantly lower in both RA groups than those in normal controls (62.1 +/- 5.7 pg/ml), P < 0.001. The results indicate that there is an inverse correlation with the plasma Beta-endorphin levels, the rheumatoid disease activity score, and the duration of RA. The depressed plasma Beta-endorphin in patients with RA may be used as an indicator of the disease activity.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Biomarkers; Female; Humans; Male; Middle Aged

To study the dynamic response of the hypothalamo-pituitary- adrenal axis and of prolactin (PRL) pituitary secretion in rheumatoid arthritis (RA).. We performed a cortisol releasing hormone (CRH) provocation test followed by determination of adrenocorticotropin hormone (ACTH), beta-endorphin, and cortisol concentration, and then a thyrotropin releasing hormone (TRH) provocation test followed by assessment of PRL pituitary secretion in 10 patients with RA and 5 control subjects. All were women under 40 years of age. Hormone concentrations were assessed by radioimmunoassay.. Basal PRL cortisol, and ACTH concentrations were similar in patients with RA and controls. We observed a dissociation between the pituitary secretion of beta-endorphin and of ACTH in response to CRH in RA. The ACTH peak and total ACTH production (area under the curve, AUC) were similar in the 2 groups. In contrast, basal beta-endorphin was increased in RA (12.6 +/- 1.41 vs 8.29 +/- 0.144 pg/ml), and the response upregulated (AUC: 83,080 +/- 12,000 vs 54,200 +/- 2400) after CRH compared to controls (p < 0.05). Cortisol adrenal response curve was blunted, but did not reach statistical significance. In contrast, the PRL response to TRH was increased at 120 and 150 min (3461 +/- 303 vs 1897 +/- 520 muIU/ml)(p < 0.01) in patients with RA, independent of disease activity.. We observed upregulated pituitary PRL secretion in RA, and a dissociation of ACTH stress. The implication concerning the neuroendocrine system in the chronic immune response in RA is discussed.

Topics: Adrenocorticotropic Hormone; Adult; Animals; Arthritis, Rheumatoid; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Prolactin; Radioimmunoassay; Reference Values; Sheep; Thyrotropin-Releasing Hormone

The presence of beta-endorphin (beta-end) was immunohistologically identified in synovial tissue samples biopsied from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The amount of beta-end in culture supernatants of synovial tissue explants was also determined by RIA. beta-end was strongly detected in mainly superficial synovial cells, vascular endothelial cells and a few synovial interstitial cells in RA patients, but not in OA patients. In RA patients the beta-end concentration was significantly higher in the supernatants of tissue explants (26.4 +/- 8.3 pg/ml) than in the plasma of the same patients (15.3 +/- 2.5 pg/ml) (p < 0.01). Using isolated synovial cells, the beta-end concentration in the culture supernatants of non-adherent cells (19.4 pg/ml) was higher than that of adherent cells (4.0 pg/ml). It is suggested that beta-end is produced by non-adherent cells such as lymphocytes and neutrophils in addition to synovial lining cells and endothelial cells and may play some role in the pathology of RA synovial inflammation.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Endorphins; Female; Humans; Immunohistochemistry; Male; Middle Aged; Osteoarthritis; Synovial Membrane

Authors have often experienced that psychological stress influences rheumatoid arthritis (RA). In addition, recent reports show a modulatory role for neuropeptide such as substance P in arthritis. These findings prompted us to study endogenous opioid peptides in RA, which are found mainly in the brain and have an effect on the central nervous system. We examined methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk) and beta-endorphin (beta-end) in opioid peptides. We measured these peptides in plasma and synovial fluid samples obtained from 28 knees of 24 RA patients and the quantity in the synovial tissue of 13 knees. We also measured plasma and synovial fluid samples from patients with osteoarthritis of the knee and plasma samples from healthy candidates. Leu-enk and beta-end levels in synovial fluid were significantly higher than plasma levels only in RA. Larger quantity of Leu-end and beta-end were contained apparently in the synovial tissue than Met-enk. The synovial tissue with proliferative change tends to contain larger quantity of opioid peptides. These results indicate that the synovial tissue produces or secretes Leu-enk and beta-end and that opioid peptides are related to the degree of inflammation in RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Enkephalin, Leucine; Enkephalin, Methionine; Female; Humans; Male; Middle Aged; Stress, Psychological; Synovial Fluid; Synovial Membrane

Previous research has suggested that a short-term (6 week) high-intensity and a subsequent long-term (1 year) low-intensity dynamic training programme in 8 patients with rheumatoid arthritis (RA) increased circulating levels of beta-endorphin (beta-EP) during the high-intensity training and of corticotropin-releasing factor (CRF) and beta-lipotropin (beta-LPH) levels during the low-intensity training, without an increase of pain experience. The present follow-up study of the patients, using the data obtained after an additional 1-year period of no standardized training as reference values, indicated that CRF levels decreased significantly (P less than 0.01) in relation to those obtained 1 year earlier. For beta-LPH and beta-EP, no corresponding decreases were noted. No significant difference concerning experience of pain over time was found. High-performance liquid chromatography demonstrated a complex elution pattern with low basal concentration of beta-LPH, which increased after 60 min of training.

Topics: Arthritis, Rheumatoid; beta-Endorphin; beta-Lipotropin; Corticotropin-Releasing Hormone; Follow-Up Studies; Humans; Physical Education and Training; Time Factors

A limited number of experiments have shown that treatment of rheumatoid arthritis by means of cooling the entire body in cryogenic chamber reduces the pain in joints affected by inflammatory process and increases their mobility. The aim of the present thesis was to try explain the mechanisms responsible for the observed improvement of the patients' condition, and an investigation of the treatment's effect on selected hemodynamic indices. Tests were carried out on 63 patients with rheumatoid arthritis mainly in the 3rd and 4th stage of illness, all of whom had been treated for 14 days, once daily, by cooling the body for two-minute periods in cryogenic chamber with temperatures ranging from -110 degrees C to -160 degrees C, followed by kinesitherapy. It was demonstrated that after a single session in the cryogenic chamber, after 7 and 14 days the level of ACTH, cortisol and beta-endorphins in blood serum rises. The level of TSH, T4, T3, GH and 6-keto-PGF1 alpha+, however, remains unchanged. The cryogenic chamber treatment does not affect the heart rate, arterial blood pressure nor the value of the left ventricle fractional shortening index and its ejection, neither does it cause of arrhythmias and ischemic changes of the heart.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Female; Hemodynamics; Humans; Hydrocortisone; Hypothermia, Induced; Male; Middle Aged; Pituitary Hormones, Anterior; Thyroid Hormones; Time Factors

Rheumatoid arthritis (RA) patients were investigated for relationships between the concentrations of various plasma opioid peptides (beta-endorphin (beta-end), methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk) and the lymphocyte subsets, serum immunoglobulins, the patient's mood or emotion, and the RA activity. A mental state and patient mood were assessed by the Cornell Medical Index (CMI) and the Face Scale. RA activity was expressed by Lansbury's index. The plasma Met-enk concentration was correlated significantly with the %Leu11+ and %Leu11+Leu7+ cells. The plasma Leu-enk concentration also correlated significantly with the %Leu2a+Leu15- cells. The plasma Leu-enk concentration and pain score were higher while the %Leu11+Leu7- cells was lower in proportion of the degree of neurosis of the RA patient as indicated by the CMI. The plasma Met-enk concentration, the %Leu2a+Leu15-, IgG, pain score and Lansbury's index were significantly higher in the group of RA patients whose facial expression was more severe. These findings suggest that enkephalins have some relationship with the patient's mood and immunologic functions, and that enkephalins have a possibility of exerting indirect effects on RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Emotions; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Facial Expression; Female; Humans; Immunoglobulins; Leukocyte Count; Lymphocytes; Male; Middle Aged

Topics: Arthritis, Rheumatoid; beta-Endorphin; Dermatitis; Humans; Immunity, Innate; Interleukin 1 Receptor Antagonist Protein; Killer Cells, Natural; Pain; Sialoglycoproteins; Stress, Physiological; Superoxide Dismutase

The relationship among therapeutically induced affective arousal, depressive symptoms, pain and beta-endorphin levels were explored on 6 patients with chronic, active rheumatoid arthritis. An ABA, n of 1 study methodology was utilized, replicated 5 times. This procedure allowed the analysis of individualized changes across time in response to the therapeutic regimen. The results indicated that the treatment regimen activated the beta-endorphin system, particularly during the early and late phases of treatment. However, beta-endorphin response had little effect on reports of subjective pain. Depressive symptoms were affected positively by the treatment but were not strongly correlated to the beta-endorphin response. The results suggest that pain and depression represent independent systems and that beta-endorphin levels serve more as stress markers than analgesics in chronic, organic pain.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Defense Mechanisms; Depression; Endorphins; Female; Gestalt Therapy; Humans; Middle Aged; Neurotic Disorders; Pain; Pain Management; Psychotherapy

In 120 patients with rheumatic disorders concomitant assays of serum and synovial fluid were done for acute phase reactants, immunoglobulins and the neuropeptide beta-endorphin. One-third of the patients with rheumatoid disease demonstrated synovial fluid levels of endorphin to be several-fold higher than serum levels, while in two-thirds the opposite results were found. These changes are discussed as adaptive or defense mechanisms. The synovial membrane is postulated to synthesize beta-endorphin.

Topics: Aged; Arthritis, Rheumatoid; beta-Endorphin; Blood Proteins; Endorphins; Female; Humans; Immunoglobulins; Male; Middle Aged; Osteoarthritis; Rheumatic Diseases; Rheumatoid Factor; Synovial Fluid

Serum beta-endorphin was assayed without knowledge of study subject category in 44 consecutive patients with primary fibromyalgia syndrome, 3 patients with rheumatoid arthritis (RA), and 30 normal controls, all females. Mean serum beta-endorphin levels were 81 +/- 28 pg/ml in patients with fibromyalgia, whereas those in normal controls and patients with RA were 73 +/- 17 pg/mg and 73 +/- 18 pg/ml, respectively. These differences were not statistically significant. Serum beta-endorphin levels did not correlate with relevant clinical variables in either fibromyalgia or RA groups.

Topics: Adolescent; Adult; Arthritis, Rheumatoid; beta-Endorphin; Circadian Rhythm; Endorphins; Female; Humans; Middle Aged; Pain; Rheumatic Diseases; Seasons; Syndrome

Topics: Arthritis, Rheumatoid; beta-Endorphin; Endorphins; Female; Flurbiprofen; Humans; Male; Osteoarthritis; Propionates