A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models

BMC Veterinary Research

Research Article

Daniela Impellizzeri¹  Rosalia Crupi¹  Enrico Gugliandolo¹  Roberta Fusco¹  Rosanna Di Paola¹  Salvatore Cuzzocrea²  Valeria Maria Morittu³  Domenico Britti³  Carlo Schievano⁴  Maurizio Evangelista⁵ 

[1] Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31-, I-98166, Messina, Italy;Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31-, I-98166, Messina, Italy;Manchester Biomedical Research Centre, Manchester Royal Infirmary, School of Medicine, University of Manchester, Manchester, UK;Department of Health Sciences V. le Europa, Campus S. Venuta, Germaneto, 88100, Catanzaro, Italy;Innovative Statistical Research SRL, Prato Della Valle 24, I-35123, Padova, Italy;Institute of Anaesthesiology and Reanimation, Catholic University of Sacred Heart, Rome, Italy;

关键词: Osteoarthritis;    Disease models;    Pain;    Inflammation;    Drug combinations;    Palmitoylethanolamide;    Quercetin;    Co-ultra micronization;    N-acylethanolamines;   

DOI  :  10.1186/s12917-017-1151-z

 received in 2017-01-18, accepted in 2017-07-27,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundOsteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark.ResultsPEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam.ConclusionThe present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

【 授权许可】

CC BY   
© The Author(s). 2017