Involvement of p38MAPK on the antinociceptive action of myricitrin in mice |
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Authors: | Meotti Flavia Carla Posser Thaís Missau Fabiana Cristina Pizzolatti Moacir Geraldo Leal Rodrigo Bainy Santos Adair R S |
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Affiliation: | Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil. |
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Abstract: | Previous studies from our group investigated the analgesic and anti-inflammatory properties of the flavonoid myricitrin. Here, we demonstrated the role of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and mitogen-activated protein kinases (MAPKs) on the antinociceptive action of myricitrin. The nociceptive response was evaluated by monitoring biting behaviour following intratecal (i.t.) administration of IL-1beta and TNF-alpha in mice. Western blot analyses of total and phosphorylated MAPKs: p38(MAPK), extracellular-signal regulated kinase (ERK1/2) and c-Jun amino-terminal kinases (JNK1/2) from the spinal cord of mice injected with cytokines were measured. Myricitrin (0.03-30mg/kg) or vehicle (control) was administered 30 min beforehand by intraperitoneal (i.p.) injection. Myricitrin pre-treatment prevented cytokine-induced biting behaviour. The calculated ID(50) of myricitrin were 6.8 (4.6-9.0) and 2.6 (0.3-4.9) mg/kg and maximal inhibition of 83+/-9 and 100+/-0% for IL-1beta and TNF-alpha, respectively. Intrathecal injection of IL-1beta and TNF-alpha significantly increased p38(MAPK) phosphorylation and this was inhibited by myricitrin treatment. Cytokines administration did not alter ERK1/2 and JNK1/2 phosphorylation. Myricitrin prevented cytokine-induced biting behaviour and inhibited p38(MAPK) phosphorylation in response to cytokines stimulation. Taken together, it suggests that the mechanism for antinociceptive action of myricitrin in response to cytokines may involve a blockage on p38(MAPK) pathway. This finding could explain, at least in part, the antinociceptive action of this flavonoid in process like neuropathic and inflammatory chronic pain. |
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Keywords: | Myricitrin Nociception Interleukin-1β Tumor necrosis factor-α Extracellular-signal regulated kinase c-Jun amino-terminal kinases p38MAPK |
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