Involvement of p38MAPK on the antinociceptive action of myricitrin in mice.
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.
Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Flavia Carla
FC
Meotti
Thaís
T
Posser
Fabiana Cristina
FC
Missau
Moacir Geraldo
MG
Pizzolatti
Rodrigo Bainy
RB
Leal
Adair R S
AR
Santos
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C008577:myricitrin; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases