Effect of orexin-A (hypocretin-1) on hyperalgesic and cachectic manifestations of experimentally induced rheumatoid arthritis in rats.

Orexin-A has been shown to modulate pain sensation and increase appetite. Rheumatoid arthritis (RA) is characterized by joint destruction, deformity, hyperalgesia, and weight reduction. Evaluate the possible effect of orexin-A on hyperalgesic and cachectic manifestations in an adjuvant-induced arthritis (AIA) rat model. Forty adult male Wistar rats were distributed among 4 groups; I, normal controls; II, rats with AIA induced by intradermal injection of Mycobacterium butyricum, but with no other treatment; III, AIA rats treated daily with an intravenous injection of orexin-A for 8 days; and IV, AIA rats treated orally with dexamethasone for 8 days. The parameters we assessed were pain-associated behavior, body mass, hind paw volume, serum levels of nerve growth factor (NGF) and neuropeptide Y (NPY). Orexin-A caused a significant reduction in pain sensation and NGF levels, and increased body mass and the levels of NPY, whereas treatment with dexamethasone led to significant reductions in paw swelling and pain sensation. Orexin-A has hypoalgesic properties and increases body mass, whereas dexamethasone has a potent anti-inflammatory effect. Therefore, the combination of orexin-A and dexamethasone should have a greater effect with respect to attenuating the manifestations and complications associated with RA.