Endomorphin-1 causes synovial hypoaemia in rat knee joints via a capsaicin-sensitive neural pathway

In joints, synthetic mu-opioids reduce inflammatory changes such as protein extravasation and associated oedema formation. However, the effect of endogenous opioid peptides on other inflammatory processes such as altered tissue blood flow has not been investigated. The present study examined the peripheral effects of the endogenous mu-opioid ligand endomorphin-1 (EM-1) on rat knee joint blood flow using laser Doppler perfusion imaging. Topical application of EM-1 (10(-16)-10(-9) mol) to exposed rat knee joints resulted in a dose-dependent increase in synovial vascular resistance with a maximum rise of 56% occurring with the 10(-9) mol dose. Destruction of unmyelinated articular afferents by capsaicin treatment completely abolished the hypoaemic effects of EM-1. These findings suggest that EM-1 acts peripherally in knee joints to decrease synovial blood flow, and this hypoaemic response is dependent on the presence of capsaicin-sensitive nerves.