Our laboratory has previously demonstrated that 1,25-dihydroxyvitamin D 3 (1,25[OH] 2 D 3 ) rapidly stimulated polyphosphoinositide (PI) hydrolysis, raised intracellular Ca 2 ϩ , and activated two Ca 2 ϩ -dependent protein kinase C (PKC) isoforms, PKC-␣ and - II in the rat large intestine. We also showed that the direct addition of 1,25(OH) 2 D 3 to isolated colonic membranes failed to stimulate PI hydrolysis, but required secosteroid treatment of intact colonocytes, suggesting the involvement of a soluble factor. Furthermore, this PI hydrolysis was restricted to the basal lateral plasma membrane of these cells. In the present studies, therefore, we examined whether polyphosphoinositide-phospholipase C-␥ (PI-PLC-␥ ), a predominantly cytosolic isoform of PI-PLC, was involved in the hydrolysis of colonic membrane PI by 1,25(OH) 2 D 3 . This isoform has been shown to be activated and membrane-associated by tyrosine phosphorylation. We found that 1,25 (
P2X3 receptors are involved with several pain conditions. Muscle pain induced by static contraction has an important socioeconomic impact. Here, we evaluated the involvement of P2X3 receptors on mechanical muscle hyperalgesia and neutrophil migration induced by static contraction in rats. Also, we evaluated whether static contraction would be able to increase muscle levels of TNF-α and IL-1β. Male Wistar rats were pretreated with the selective P2X3 receptor antagonist, A-317491, by intramuscular or intrathecal injection and the static contraction-induced mechanical muscle hyperalgesia was evaluated using the Randall-Selitto test. Neutrophil migration was evaluated by measurement of myeloperoxidase (MPO) kinetic-colorimetric assay and the cytokines TNF-α and IL-1β by enzyme-linked immunosorbent assay. Intramuscular or intrathecal pretreatment with A-317491 prevented static contraction-induced mechanical muscle hyperalgesia. In addition, A-317491 reduced static contraction-induced mechanical muscle hyperalgesia when administered 30 and 60 min of the beginning of static contraction, but not after 30 and 60 min of the end of static contraction. Intramuscular A-317491 also prevented static contraction-induced neutrophil migration. In a period of 24 h, static contraction did not increase muscle levels of TNF-α and IL-1β. These findings demonstrated that mechanical muscle hyperalgesia and neutrophil migration induced by static contraction are modulated by P2X3 receptors expressed on the gastrocnemius muscle and spinal cord dorsal horn. Also, we suggest that P2X3 receptors are important to the development but not to maintenance of muscle hyperalgesia. Therefore, P2X3 receptors can be pointed out as a target to musculoskeletal pain conditions induced by daily or work-related activities.
Resumo A obesidade e a dor apresentam grande prevalência na população mundial. Quando associadas, as complicações são impactantes e resultam em importantes prejuízos socioeconômicos. Apesar das suas relevâncias clínicas, não está claro se a obesidade aumenta ou diminui a sensibilidade dolorosa. Portanto, o objetivo do presente estudo foi analisar o perfil doloroso de animais submetidos a dieta hiperlipídica e o possível envolvimento do sistema opióide periférico na modulação da resposta dolorosa. Os resultados demonstraram que animais submetidos ao consumo de dieta hiperlipídica apresentam diminuição da sensibilidade dolorosa a estímulos inflamatórios, e que essa hipoalgesia não é modulada pelo sistema opióide periférico.
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