Mousa Shaaban A, Straub Rainer H, Schäfer Michael, Stein Christoph
Klinik für Anaesthesiologie und Operative Intensivmedizin, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Ann Rheum Dis. 2007 Jul;66(7):871-9. doi: 10.1136/ard.2006.067066. Epub 2007 Feb 26.
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.
关节腔内应用阿片类激动剂或拮抗剂可调节膝关节手术后及慢性关节炎患者的疼痛。因此，对关节创伤（JT）、骨关节炎（OA）和类风湿关节炎（RA）患者滑膜内β-内啡肽（END）、甲硫氨酸脑啡肽（ENK）以及μ和δ阿片受体（ORs）的表达进行了检测。
对滑膜样本进行阿片肽与免疫细胞标志物的双重免疫组化分析，以及ORs与神经元标志物降钙素基因相关肽（CGRP）和酪氨酸羟化酶（TH）的双重免疫组化分析。
在所有疾病的滑膜衬里层中，巨噬细胞样（CD68(+)）和成纤维细胞样（CD68(-)）细胞表达END和ENK。在滑膜下层，JT患者中END和ENK主要由粒细胞表达，而OA和RA患者中则由巨噬细胞/单核细胞、淋巴细胞和浆细胞表达。总体而言，RA患者中END和ENK免疫反应性（IR）细胞比OA和JT患者更为丰富。在所有患者的神经纤维和免疫细胞上均发现了ORs。RA患者中OR-IR神经纤维明显比OA和JT患者更为丰富。μORs和δORs与CGRP共表达，但不与TH共表达。
与炎症严重程度平行，RA患者免疫细胞中的END和ENK及其感觉神经末梢上的受体比JT和OA患者更为丰富。这些发现与以下观点一致，即随着炎症的持续和加重，免疫和外周神经系统上调表达ORs及其配体的感觉神经，以平衡疼痛和炎症。
