beta-endorphin and Osteoarthritis

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

The major clinical guidelines recommend the use of acetaminophen (acetyl-para-aminophenol [APAP]) for the treatment of mild-to-moderate symptoms of osteoarthritis (OA) and only recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs) after APAP failure. This recommendation is based on the efficacy of APAP in treating OA and its relatively benign side-effect profile compared with NSAIDs. NSAIDs are associated with a high risk of adverse events, particularly those of the gastrointestinal (GI) tract. A large number of studies in OA have compared APAP with a variety of selective and nonselective NSAIDs and typically found greater efficacy with NSAIDs. This advantage, however, is mainly the result of increased efficacy in patients with more severe disease, and is viewed as a relatively small analgesic advantage in some studies and meta-analyses. Many of these same studies have reported little or no difference in safety between APAP and NSAIDs, but these results are typically based on short-term studies. Results from meta-analyses on the safety of NSAIDs almost unanimously confirm elevated risk of GI complications. The analgesic mechanism of APAP is still not well understood. However, the notion that APAP has no anti-inflammatory effect has been challenged in recent years with increasing data that suggest it may have an effect on inflammation distinct from that seen with NSAIDs. A variety of mechanistic hypotheses have been proposed.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; beta-Endorphin; Humans; Nitric Oxide; Osteoarthritis; Substance P

Radon therapy uses radon (222Rn) gas, which mainly emits alpha-rays and induces a small amount of active oxygen in the body. We first examined the temporal changes in antioxidants, immune, vasoactive, and pain-associated substances in human blood by therapy to elucidate the mechanism of osteoarthritis in which radon therapy is used as a treatment. Results showed that radon inhalation enhanced the antioxidation and immune function, and the findings suggest that radon therapy contributes to the prevention of osteoarthritis related to peroxidation reactions and immune depression. Moreover, the changes in vasoactive and pain-associated substances indicated increases in tissue perfusion brought about by radon therapy, suggesting that radon inhalation plays a role in alleviating pain.. The findings suggest that an appropriate amount of active oxygen is produced in the body after radon inhalation, and this contributes to the alleviation of the symptoms of active oxygen diseases such as osteoarthritis.

Topics: Aged; Air Pollutants, Radioactive; Antioxidants; Atrial Natriuretic Factor; beta-Endorphin; Female; Humans; Hyperthermia, Induced; Immunologic Factors; Male; Middle Aged; Osteoarthritis; Pilot Projects; Radon; Time Factors

Chronic pain conditions, especially osteoarthritis (OA), are as common in individuals with Alzheimer's disease (AD) as in the general elderly population, which results in detrimental impact on patient's quality of life. However, alteration in perception of pain in AD coupled with deteriorating ability to communicate pain sensations often result in under-diagnosis and inappropriate management of pain. Therefore, a better understanding of mechanisms in chronic pain processing in AD is needed. Here, we explored the development and progression of OA pain and the effect of analgesics in a transgenic mouse model of AD.. Unilateral OA pain was induced chemically, via an intra-articular injection of monosodium iodoacetate (MIA) in the left knee joint of AD-mice (TASTPM) and age- and gender-matched C57BL/6J (WT). Pharmacological and biochemical assessments were conducted in plasma and spinal cord tissue.. MIA resulted in hind paw mechanical hypersensitivity (allodynia), initiating on day 3, in TASTPM and WT controls. However, from 14 to 28 days, TASTPM displayed partial attenuation of allodynia and diminished spinal microglial response compared to WT controls. Naloxone, an opioid antagonist, re-established allodynia levels as observed in the WT group. Morphine, an opioid agonist, induced heightened analgesia in AD-mice whilst gabapentin was devoid of efficacy. TASTPM exhibited elevated plasma level of β-endorphin post-MIA which correlated with impaired allodynia.. These results indicate an alteration of the opioidergic system in TASTPM as possible mechanisms underlying impaired persistent pain sensitivity in AD. This work provides basis for re-evaluation of opioid analgesic use for management of pain in AD.. This study shows attenuated pain-like behaviour in a transgenic mouse model of Alzheimer's disease due to alterations in the opioidergic system and central plasticity mechanisms of persistent pain.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Analgesics; Analgesics, Opioid; Animals; Arthralgia; Behavior, Animal; beta-Endorphin; Chronic Pain; Disease Models, Animal; Enzyme Inhibitors; Gabapentin; Humans; Hyperalgesia; Injections, Intra-Articular; Iodoacetic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Morphine; Naloxone; Narcotic Antagonists; Osteoarthritis; Pain Measurement; Pain Threshold; Quality of Life; Spinal Cord

Analgesia with opioids such as morphine is an effective clinical strategy for the treatment of cancer pain and chronic inflammatory pain. However, long-term use of morphine can cause morphine tolerance (MT), which limits the clinical application of opioids. Polysaccharopeptide from Trametes versicolor (TPSP) is a biologically active macromolecule that exerts anti-tumor, immune-enhancing and pain-relieving effects. In order to address the clinical problem of MT, herein, we investigated the inhibitory effect and mechanism of TPSP in rats with inflammatory pain-morphine tolerance. A chronic inflammatory osteoarthritis pain-morphine tolerance model was simulated by injection of complete Freund's adjuvant (CFA) through the ankle joint cavity and continuous intrathecal administration of morphine. Different doses of TPSP (50 μg/kg, 100 μg/kg and 200 μg/kg) were intrathecally administered for consecutive 3 weeks. Our results indicate that TPSP can significantly inhibit the development of morphine dependence and acute withdrawal in rats, alleviate the decrease of paw withdrawal mechanical threshold and heat stimulation retraction latency. In addition, mechanistically at the molecular level, these effects are elicited via up-regulation of the cannabinoid type 2 receptor, up-regulating the level of β-endorphin, and reducing the levels of IL-1, NO and PGE

Topics: Animals; Behavior, Animal; beta-Endorphin; Dinoprostone; Down-Regulation; Inflammation; Interleukin-1; Male; Morphine; Nitric Oxide; Osteoarthritis; Pain; PC12 Cells; Proteoglycans; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Recombinant Proteins; Trametes

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

Topics: Acetaminophen; Analgesics, Non-Narcotic; beta-Endorphin; Humans; Osteoarthritis

Thermal mud is a therapeutic agent widely used in the treatment of painful arthritic processes. The mechanism by which mud therapy works is still not well known. Its effect continues for months after completion of treatment. In order to verify whether thermal mud treatment brings about changes in the production of hormone peptides from proopiomelanocortin, the levels of plasma beta-endorphin and some hormones of the pituitary-adrenal glands (ACTH and cortisol) were determined in patients affected by osteoarthritis undergoing thermal mud therapy.. The levels of plasma beta-endorphin and some hormones of the pituitary-adrenal glands (ACTH and cortisol) were assessed by radiometric methods in seventeen males affected by osteoarthritis. The patients underwent a cycle of twelve sessions of thermal mud therapy. The tests were carried out immediately before thermal treatment, immediately after the first session, twelve days after the start of treatment, and again one month after completion of the treatment.. beta-endorphin levels decreased significantly twelve days after the start of treatment. The level was still lower, although not significantly, even thirty days after completion of the treatment. Plasma ACTH also decreased during treatment. The decrease of this hormone was progressive and persisted after completion of treatment. Significant variations compared to baseline were found only thirty days after completion of treatment. Plasma cortisol decreased significantly after only one session of mud therapy. This hormone did not decrease any further during treatment, however, after twelve days it was still significantly lower than baseline. After completion of treatment, cortisol slightly increased, but thirty days later it was still lower, although not significantly, than baseline.. It may be suggested that thermal treatment, by reducing inflammation, reduced pain and therefore diminished the cause of stress.

Topics: Adrenocorticotropic Hormone; Aged; beta-Endorphin; Humans; Hydrocortisone; Male; Middle Aged; Mud Therapy; Osteoarthritis; Pituitary-Adrenal System; Treatment Outcome

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

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

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

Plasma levels of the endogenous opioid peptides beta-endorphin and [Met]enkephalin were estimated in 10 osteoarthritic patients during treatment with a sustained-release indomethacin preparation (Osmosin). Significant diurnal variation of beta-endorphin levels was evident both on and off treatment (p less than 0.05, respectively), but the therapy was nevertheless accompanied by decreased morning levels of this peptide; no such changes were recorded for [Met)enkephalin. Whilst the treatment was associated with a reduction of pain, particularly in the evening (p less than 0.02), no correlation was evident between pain and beta-endorphin levels, nor between the patients' perception of pain relief and changes in beta-endorphin levels. The results suggest either that prostaglandins may be involved in the synthesis/release of beta-endorphin, or that the alleviation of stress may in turn reduce the need for continued beta-endorphin production in these patients.

Topics: Aged; Anti-Inflammatory Agents; beta-Endorphin; Delayed-Action Preparations; Endorphins; Enkephalin, Methionine; Female; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Pain

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