Abstract
BackgroundOsteoarthritis (OA) is a degenerative joint disease produced by a cascade of events that can ultimately lead to joint damage. The aim of this study was to evaluate the effect of adelmidrol, a synthetic palmitoylethanolamide analogue, combined with hyaluronic acid on pain severity and modulation of the inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis.MethodsOA was induced by intra-articular injection of MIA in the knee joint. On day 21 post-MIA administration, the knee joint was analyzed. Rats subjected to OA were treated by intra-articular injection of adelmidrol in combination with sodium hyaluronate at different doses and time points after MIA induction. Limb nociception was assessed by the paw withdrawal latency and threshold measurement. Samples were examined macroscopically, histologically, and by immunohistochemistry.ResultsAt day 21 post-MIA injection, the MIA + solvent and MIA + 1.0% sodium hyaluronate groups showed irregularities and fibrillation in the surface layer, a decrease in blood cells and multilayering in transition and radial zones, no pannus formation, and modified Mankin scores significantly higher than sham knees. The combination of hyaluronic acid and adelmidrol dose-dependently (adelmidrol 0.6% + 1.0% sodium hyaluronate and adelmidrol 2% + 1.0% sodium hyaluronate) reduced the histological alterations induced by MIA. Moreover, degeneration of articular cartilage, mast cell infiltration, and pro-inflammatory cytokine and chemokine plasma levels were significantly downregulated by treatment with a combination of hyaluronic acid and adelmidrol at the above doses.ConclusionsOur results clearly demonstrate that the combination of hyaluronic acid and adelmidrol improves the signs of OA induced by MIA.
Highlights
Osteoarthritis (OA) is a degenerative joint disease produced by a cascade of events that can lead to joint damage
In the von Frey hair assessment test, the paw withdrawal latency (PWL) (Fig. 1b) and the paw withdrawal threshold (PWT) (Fig. 1a) were significantly prolonged in the inflamed hind paw of the rats given 0.6% adelmidrol + 1.0% sodium hyaluronate and 2% adelmidrol + 1.0% sodium hyaluronate compared with the monosodium iodoacetate (MIA)
Our results clearly demonstrated that a combination of hyaluronic acid (HA) and adelmidrol dose-dependently produced a significant reduction in: 1) pain severity; 2) OA histopathology; 3) articular cartilage degeneration; 4) mast cell infiltration; 5) pro-inflammatory cytokines, matrix metalloproteinase (MMP), and nerve growth factor (NGF) production; and 6) the degree of motor function
Summary
Osteoarthritis (OA) is a degenerative joint disease produced by a cascade of events that can lead to joint damage. The aim of this study was to evaluate the effect of adelmidrol, a synthetic palmitoylethanolamide analogue, combined with hyaluronic acid on pain severity and modulation of the inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. Osteoarthritis (OA) is one of the most common joint disabling disorders in adults [1] It occurs when the protective cartilage on the ends of bones breaks down, causing pain, swelling, and problems in joint articulation [2]. Nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids reduce the OA symptoms of joint pain and swelling [9]. Important evidence shows that GCs are used in association with hyaluronic acid (HA) and partially show an ability to reduce pain as well as the progression of disease [14]. A number of studies suggest that HA associated with GCs might have a beneficial effect partially related to a viscoelastic lubricant effect [15, 16]
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