Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis
Female; Humans; Male; Adult; Aged; Middle Aged; 80 and over; Arthritis; Biomarkers of Pain; Opioid; Receptors; Biological Markers/analysis; beta-Endorphin/analysis; Enkephalin; Methionine/analysis; Immunohistochemistry/methods; Arthritis/immunology/metabolism; delta/analysis; Joints/immunology/injuries; Leukocytes/immunology; mu/analysis; Opioid/analysis; Osteoarthritis/immunology/metabolism; Rheumatoid/immunology/metabolism; Synovial Membrane/chemistry/immunology
OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
2007
Mousa SA; Straub RH; Schafer M; Stein C
Annals Of The Rheumatic Diseases
2007
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1136/ard.2006.067066" target="_blank" rel="noreferrer">10.1136/ard.2006.067066</a>
Control of inflammatory pain by chemokine-mediated recruitment of opioid-containing polymorphonuclear cells
Male; Pain Measurement; Analysis of Variance; Animals; Rats; Non-U.S. Gov't; Research Support; Comparative Study; Dose-Response Relationship; Drug; Receptors; Naloxone/pharmacology; Freund's Adjuvant; Wistar; Flow Cytometry/methods; Antibodies/pharmacology; Cell Count/methods; Cell Movement/physiology; Chemokines; Chemokines/immunology/physiology; Corticotropin-Releasing Hormone/therapeutic use; CXC/immunology/metabolism; Drug Administration Routes; Enzyme-Linked Immunosorbent Assay/methods; Gene Expression Regulation/physiology; Immunohistochemistry/methods; Intercellular Signaling Peptides and Proteins/immunology/metabolism; Interleukin-8B/metabolism; Narcotics/metabolism; Neurogenic Inflammation/chemically induced/complications/therapy; Neutrophils/metabolism; Pain Threshold/drug effects; Pain/etiology/therapy
Opioid-containing leukocytes can counteract inflammatory hyperalgesia. Under stress or after local injection of corticotropin releasing factor (CRF), opioid peptides are released from leukocytes, bind to opioid receptors on peripheral sensory neurons and mediate antinociception. Since polymorphonuclear cells (PMN) are the predominant opioid-containing leukocyte subpopulation in early inflammation, we hypothesized that PMN and their recruitment by chemokines are important for peripheral opioid-mediated antinociception at this stage. Rats were intraplantarly injected with complete Freund's adjuvant (CFA). Using flow cytometry, immunohistochemistry, and ELISA, leukocyte subpopulations, chemokine receptor (CXCR2) expression on opioid-containing leukocytes and the CXCR2 ligands keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant-2 (CINC-2) were quantified. Paw pressure threshold (PPT) was determined before and after intraplantar and subcutaneous injection of CRF with or without naloxone. PMN depletion was achieved by intravenous injection of an antiserum. Chemokines were blocked by intraplantar injection of anti-MIP-2 and/or anti-KC antiserum. We found that at 2 h post CFA (i) intraplantar but not subcutaneous injection of CRF produced dose-dependent and naloxone-reversible antinociception (P0.05, ANOVA). In summary, in early inflammation peripheral opioid-mediated antinociception is critically dependent on PMN and their recruitment by CXCR2 chemokines.
2004
Brack A; Rittner HL; Machelska H; Leder K; Mousa SA; Schafer M; Stein C
Pain
2004
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/j.pain.2004.08.029" target="_blank" rel="noreferrer">10.1016/j.pain.2004.08.029</a>