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

Abstract

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.

The Antioxidant and Anti-Inflammatory Properties of Anacardium occidentale L. Cashew Nuts in a Mouse Model of Colitis

“…CAR -induced paw edema was performed as previously indicated by a subplantar injection of CAR (0.1 mL/rat of a 1% suspension in saline) (Sigma-Aldrich, Milan, Italy) into the right hind paw [30]. Increase in paw volume (mL) was measured using a plethysmometer (Ugo Basile, Varese, Italy) immediately prior to the CAR injection and at 30 min and each hour for 6 h.…”

Utilizing Liposomal Quercetin and Gallic Acid in Localized Treatment of Vaginal Candida Infections

“…In addition, its inhibitory effects on cytokine production (i.e., TNF-α and IL-8) and histamine release [15] lead to a reduction of the inflammation state. Moreover, several groups [16,17] have also suggested that quercetin may be an antinociceptive in animal models, thus relieving the pain associated with inflammation. Interestingly, Maramaldi et al [18] demonstrated that phytosomes containing quercetin were able to exert a lenitive and anti-itch effect in a group of volunteers with skin damage.…”

<p>Validation of the Key Active Ingredients and Anti-Inflammatory and Analgesic Effects of Shenjin Huoxue Mixture Against Osteoarthritis by Integrating Network Pharmacology Approach and Thin-Layer Chromatography Analysis</p>

“…According to several studies, quercetin had protective effects on anti-inflammation and relieved the accompanying symptoms such as pain related to OA. 27,28 What's more, paeoniflorin has been reported as protective effects against OAwith anti-apoptosis and anti-inflammation effects on chondrocyte. 29,30 As for other key active ingredients, formononetin existing in HL and RG has been proved the anti-catabolic effects on rat chondrocytes and articular cartilage, 31 and it dose-dependently decreased IL-6 in OA subchondral osteoblasts.…”