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Background: Osteoarthritis (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. Results: PEA-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. Conclusion: The 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. [ABSTRACT FROM AUTHOR]

Background: Chronic widespread pain conditions (CWP) such as the pain associated with fibromyalgia syndrome (FMS) are significant health problems with unclear aetiology. Although CWP and FMS can alter both central and peripheral pain mechanisms, there are no validated markers for such alterations. Pro- and anti-inflammatory components of the immune system such as cytokines and endogenous lipid mediators could serve as systemic markers of alterations in chronic pain. Lipid mediators associated with anti-inflammatory qualities - e.g., oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) - belong to N-acylethanolamines (NAEs). Previous studies have concluded that these lipid mediators may modulate pain and inflammation via the activation of peroxisome proliferator activating receptors (PPARs) and the activation of PPARs may regulate gene transcriptional factors that control the expression of distinct cytokines. Methods: This study investigates NAEs and cytokines in 17 women with CWP and 21 healthy controls. Plasma levels of the anti-inflammatory lipids OEA, PEA, and SEA, the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 were investigated. T-test of independent samples was used for group comparisons. Bivariate correlation analyses, and multivariate regression analysis were performed between lipids, cytokines, and pain intensity of the participants. Results: Significantly higher levels of OEA and PEA in plasma were found in CWP. No alterations in the levels of cytokines existed and no correlations between levels of lipids and cytokines were found. Conclusions: We conclude that altered levels of OEA and PEA might indicate the presence of systemic inflammation in CWP. In addition, we believe our findings contribute to the understanding of the biochemical mechanisms involved in chronic musculoskeletal pain. [ABSTRACT FROM AUTHOR]

Background: Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and anti-nociceptive compounds, and such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women.Methods: Blood samples from 35 women with NP, 15 with CWP and 27 age-matched controls were analysed for the lipids using ultra performance liquid chromatography coupled to tandem mass spectrometry. Current pain ("NRSday") and the average pain during the last week ("NRSweek") were rated by the participants using a numerical rating scale.Results: There were no significant differences in the plasma concentrations of the fifteen lipids investigated between the women with pain and the controls. However, significant correlations were seen for the NP group between the NRSday scores and the plasma concentrations of the linoleic acid derivatives 9- and 13-hydroxy-octadecadienoic acid (Spearman's rho values 0.51 [P = 0.0016]) and 0.53 [P = 0.0011], respectively).Conclusions: The data obtained in this exploratory study indicate that although no group differences are seen in plasma lipid concentrations, there is an association between the NRSday scores and the 9- and 13-hydroxy-octadecadienoic acid levels. Whether or not the association reflects a causality (i.e. that the circulating lipids contribute to the perceived pain of the pain participants), requires further investigation. [ABSTRACT FROM AUTHOR]

We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m2, age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. [ABSTRACT FROM AUTHOR]