title: Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats.
abstract: Osteoarthritis (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.
  
  
  
  OA 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.
  
  
  
  At 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.
  
  
  
  Our results clearly demonstrate that the combination of hyaluronic acid and adelmidrol improves the signs of OA induced by MIA.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, n 31, Messina, 98166, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, n 31, Messina, 98166, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fusco
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, n 31, Messina, 98166, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, n 31, Messina, 98166, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Health Science, University of Catanzaro, Viale Europa, Campus S. Venuta, Germaneto, Catanzaro, 88100, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.affiliation: Department of Health Science, University of Catanzaro, Viale Europa, Campus S. Venuta, Germaneto, Catanzaro, 88100, Italy.
authors.forename: Valeria Maria
authors.initials: VM
authors.lastname: Morittu
authors.affiliation: Institute of Anaesthesiology and Reanimation, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Evangelista
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, n 31, Messina, 98166, Italy. salvator@unime.it.|Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St. Louis, MO, 63104, USA. salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000473:pathology*; D003998:Dicarboxylic Acids / Q000008:administration & dosage*; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D019807:Iodoacetic Acid / Q000633:toxicity; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000473:pathology*; D010169:Palmitic Acids / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D003998:Dicarboxylic Acids; D010169:Palmitic Acids; C552602:adelmidrol; D006820:Hyaluronic Acid; D019807:Iodoacetic Acid
keywords: Adelmidrol; Cartilage degeneration; Inflammation; Osteoarthritis; Sodium hyaluronate