RESUMEN
OBJECTIVES: In the current study, we have evaluated the intermittent cold stress (ICS) induction in mice, in order to validate and optimize its utility as a fibromyalgia-like model. METHODS: Twenty-four mice of 5-week old, female Swiss, weighing 18-22 g were used for the experiments. These mice were divided into three groups of eight animals per group [health control group (control), ICS group (ICS), and Gabapentin group (GBP)]. When in-vivo tests were completed, we proceeded to isolation and culture of peritoneal macrophages in order to determine the effects of the ICS on the release of proinflammatory mediators. RESULTS: The results showed that this model is suitable to induce mechanical allodynia, thermal allodynia, and hyperalgesia. It is also able to reproduce behavioral changes related to cognitive disturbances, anxiety, and depression. Besides, ICS model might increase the inflammatory response in LPS-macrophages stimulated from stressed mice. CONCLUSIONS: Our results show that ICS is a useful animal model to assess hypothesis about underlying mechanisms involved in the development of fibromyalgia as well as to evaluate possible future therapies.
Asunto(s)
Modelos Animales de Enfermedad , Fibromialgia/fisiopatología , Hiperalgesia/fisiopatología , Macrófagos Peritoneales/metabolismo , Aminas , Animales , Ácidos Ciclohexanocarboxílicos , Dinoprostona/metabolismo , Femenino , Fibromialgia/etiología , Fibromialgia/metabolismo , Gabapentina , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Ratones , Óxido Nítrico/metabolismo , Ácido gamma-AminobutíricoRESUMEN
Hempseed (Cannabis sativa L.) has beneficial impact on human health mainly because of its wide variability of bioactive compounds. However, many of them are not fully characterized yet. In this work, hempseed was defatted and through a bio-guided studied, two fractions (F03 and F05) with the highest content of phenols, flavonoids and antioxidant capacity were selected. Fractions were chemically analyzed by UHPLC HRMS/MS. The anti-inflammatory capacities of these compounds were evaluated on human monocytes using flow cytometry, RT-qPCR and Elisa procedures. A high amount of phenolic compounds were identified, with the major compound being: N-trans-caffeoyltyramine (6.36 mg g-1 in F05 and 1.28 mg g-1 in F03). Both, F03 and F05 significantly reduced the inflammatory competence of LPS-treated human primary monocytes, decreasing TNF-α and IL-6 gene expression and secretion. These findings indicate that in the defatted fraction of the hempseed there are a wide number of compounds with beneficial potential to prevent and treat inflammatory disorders, as well as other processes caused by oxidative stress.