Abstract
Objective
Pain sensitization and the related secretion of neuropeptides from sensory nerve terminals are proinflammatory in osteoarthritis (OA), rheumatoid arthritis (RA), and adjuvant‐induced polyarthritis. In contrast, endogenous opioids such as the recently discovered endomorphins (EMs) are antiinflammatory. However, the role of endogenous EMs such as EM‐1 and EM‐2 has never been investigated in OA and RA.
Methods
We established a highly sensitive radioimmunoassay to detect EM‐1 and EM‐2. In patients with RA and patients with OA, immunohistochemistry for EM‐1 and EM‐2 was performed, and double‐staining was used to identify EM‐positive cells. The effects of EM‐1 and EM‐2 on the secretion of interleukin‐6 (IL‐6) and IL‐8 from human synovial tissue were studied by tissue superfusion, and the therapeutic effects of EM‐1 were tested in a rat model of adjuvant‐induced polyarthritis.
Results
EM‐positive cells were located in the sublining area and vessel walls but were particularly evident in the highly inflamed lining area. Human macrophages, T cells, and fibroblasts stained positive for EMs. The synovial density of EM‐positive cells was higher in patients with OA than in those with RA. EM‐1 inhibited synovial secretion of IL‐6 in patients with RA and secretion of IL‐8 in patients with RA and those with OA (maximum 10^−10^M). EM‐2 inhibited IL‐8 secretion only from RA tissue (maximum 10^−10^M). In rats with adjuvant‐induced polyarthritis, thymus, spleen, and synovial tissue contained significantly more EM‐1 than was observed in controls. Rats with adjuvant‐induced polyarthritis benefited from EM‐1 treatment.
Conclusion
EM‐1 had antiinflammatory effects in patients with OA or RA and in a model of adjuvant‐induced polyarthritis. Local enhancement of EM‐1 might be an interesting therapeutic option in different forms of arthritis.