B-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis

Shaaban A Mousa Ph.D.^1*, Rainer H Straub MD², Michael Schäfer MD¹ and Christoph Stein MD¹

¹ Freie Universität Berlin, Charité Campus Benjamin Franklin, Germany
² Lab. NeuroEndocrinoImmunology, Germany

^* To whom correspondence should be addressed. E-mail: shaaban.mousa{at}charite.de.

Accepted 19 February 2007

Abstract

Objective: Intraarticularly applied opioid agonists or antagonists modulate pain after knee surgery and in chronic arthritis. Therefore, we examined the expression of b-endorphin (END), Met-enkephalin (ENK), mu- (m) and delta- (d) opioid receptors (OR) within synovium of patients with joint trauma (JT), osteoarthritis (OA) and rheumatoid arthritis (RA).

Methods: Synovial samples were subjected to double immunohistochemical analysis of opioid peptides with immune cell markers, and of OR 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 JT, and by macrophages/monocytes, lymphocytes and plasma cells in OA and RA. Overall, END- and ENK-immunoreactive (ir) cells were more abundant in RA than in OA and JT. OR were found on nerve fibers and immune cells in all patients. OR-ir nerve fibers were significantly more abundant in RA than in OA and JT. mOR and dOR were co-expressed with CGRP but not with TH.

Conclusions: Parallel to the severity of inflammation, END, ENK in immune cells and their receptors on sensory nerve terminals are more abundant in RA than in JT and OA. These findings are consistent with the notion that, with prolonged and enhanced inflammation, the immune and peripheral nervous systems up-regulate sensory nerves expressing OR and their ligands to counterbalance pain and inflammation.

Keywords: arthritis, human synovium, immunohistochemistry, opioid peptides, opioid receptor

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