beta-endorphin and Synovitis

Opioids produce analgesia by interacting with local opioid receptors in peripheral inflamed tissue. This study investigated whether endogenous ligands of these receptors are present in synovia and whether such opioid peptides can inhibit pain by activation of intra-articular opioid receptors. Samples of synovium from 8 patients undergoing arthroscopic knee surgery were examined by immunohistochemistry for the presence of beta-endorphin, met-enkephalin, and dynorphin. All tissue samples showed synovitis. Inflammatory cells stained strongly for beta-endorphin and met-enkephalin but not for dynorphin. To find out whether blockade of intra-articular opioid receptors affected pain, we randomly assigned 22 patients undergoing arthroscopic knee surgery to receive naloxone (0.04 mg) intra-articularly (n = 10) or intravenously (n = 12); each patient received a placebo injection into the other site. Postoperative pain was assessed by visual analogue scale, a numerical rating scale, the McGill pain questionnaire, and supplementary analgesic consumption during the next 24 h. All pain scores were higher in the intra-articular naloxone group than in the intravenous naloxone group. The differences were significant (p < 0.05) during the first 4 h. Supplementary analgesic consumption was significantly higher in the intra-articular group (52.5 [14.0] vs 15.6 [8.0] mg diclofenac, p < 0.05). Opioid peptides are present in inflamed synovial tissue and can inhibit pain after knee surgery through an action specific to intra-articular opioid receptors. These findings expand the gate control theory of pain and suggest new approaches such as the development of peripherally acting opioid analgesics without central side-effects.

Topics: Adult; Aged; Arthroscopy; beta-Endorphin; Double-Blind Method; Dynorphins; Endorphins; Enkephalin, Methionine; Humans; Immunohistochemistry; Injections, Intra-Articular; Injections, Intravenous; Knee Joint; Middle Aged; Naloxone; Pain, Postoperative; Receptors, Opioid; Synovial Membrane; Synovitis

To investigate the presence of endogenous beta-endorphin, an opioid, in the synovial lavage fluid of the temporomandibular joint (TMJ), and to compare the concentration of 3-endorphin in patients with closed lock with that in symptom-free subjects.. Thirty-eight patients (38 joints) with closed lock diagnosed on the basis of the results of clinical examination and magnetic resonance imaging (MRI) and 11 healthy volunteers (19 joints) were examined. Samples of lavage fluid were obtained prior to arthrocentesis by washing the joint with saline. Samples were assayed for beta-endorphin by an enzyme immunoassay, and concentrations of protein were measured by a bicinchoninic acid assay. Subjective pain was assessed by patients using a visual analog scale. Bone changes in the condyle were assessed by MRI, and synovitis was assessed on the basis of arthroscopic findings.. beta-endorphin was present in the synovial fluid of the TMJ, and the concentration was significantly higher in patients with closed lock of the TMJ compared to symptom-free volunteers. The beta-endorphin levels were not, however, significantly correlated with clinical parameters in the patients.. The study results support recent findings that some opioids and their receptors exist not only within the central nervous system but also in the TMJ region, and that opioid concentrations are higher in patients with pain and dysfunction of the TMJ.

Topics: Adolescent; Adult; Aged; beta-Endorphin; Case-Control Studies; Facial Pain; Female; Humans; Immunoenzyme Techniques; Indicators and Reagents; Joint Dislocations; Male; Mandibular Condyle; Middle Aged; Pain Measurement; Quinolines; Sex Factors; Statistics, Nonparametric; Synovial Fluid; Synovitis; Temporomandibular Joint Disorders

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