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-1β (IL-1β), tumor necrosis factor-α (TNF-α) 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-1β and TNF-α in mice. Western blot analyses of total and phosphorylated MAPKs: p38MAPK, 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 (0.03–30 mg/kg) or vehicle (control) was administered 30 min beforehand by intraperitoneal (i.p.) injection. Myricitrin pre-treatment prevented cytokine-induced biting behaviour. The calculated ID50 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-1β and TNF-α, respectively. Intrathecal injection of IL-1β and TNF-α significantly increased p38MAPK 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 p38MAPK 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 p38MAPK pathway. This finding could explain, at least in part, the antinociceptive action of this flavonoid in process like neuropathic and inflammatory chronic pain.