PI3K activation occurs in neurons Hedgehog Signaling Pathwy of the spinal cord, which seems to be a first step, and is responsible for the activation of ERK, perhaps inneurons. It is not clear to what Cells in the spinal cord JNK is activated after injection of formalin into the paw, w Occurs during the activation of p38 Haupts Chlich in the microglia, when the activation is also detected, to a lesser Ausma In astrocytes and neurons. In view of the same pharmacological sensitivity of kinase inhibitors and microglia in formaldehyde, acetic Acid and models of PBQ, it is m Possible that these peripheral stimuli to induce cracking and twisting through the activation Similar mechanisms vertebra Column, confinement Lich cells and kinases, to warrant further investigation. Term best, In a model of visceral pain induced by intrarectal administration H2 Receptors of formalin, there is the activation of p38 and c spinal Fos expression. Thus, visceral formalin administration activate Similar mechanisms of the vertebra Molecules that injection of formalin into the paw as well as acetic Acid or intraperitoneal administration PBQ on Similar mechanisms such as injection of formalin into the paw or activate appears intrarectal. It is important, we have shown that no intrathecal treatment indicates with kinase inhibitors tested here, Ver Changes of mechanical hyperalgesia to the lateral G-CSF stimulation that PD98059, SB600125, SB202190 and wortmannin MODIFIED Not alter the basic mechanical threshold from normal tissue. Thus, it is unlikely that these inhibitors would affect basal visceral reaction at the doses tested. MAP kinase and / or inhibitors of PI3K inhibitors and microglia used here reduced to 60% and 35% vinegar Acid and to induce 80% and 48% of the reaction of PBQ writhing, respectively. It is m Possible that lead h Higher doses of inhibitors k Nnte the abolition of nociception, we k But can not h To use higher doses than those in the literature in order not to lose their selectivity T. The result shows that the combined treatment with doses that are ineffective as a single treatment abolished vinegar Acid acidand PBQ induced writhing and formalin-induced flinch response L Sst an r The sequential and / or synergistic vertebra Molecules p38, ERK, JNK and PI3K in these nociceptive responses. Substantiate a sequential order and the interaction of PI3K and MAP kinase, PI3K activates ERK in primary Ren sensory neurons induced Warmth and mechanical hyperalgesia and spinal cord mediation of formalin nociception. MAP kinases another interaction between them can in terms of relationship PI3K/MAP kinases, since they act in a mutually dependent Ngigen k To transcription factors such as activating protein 1, to activate JNK and ERK as. On the other hand, p38, JNK and ERK, generally do not activate each other. Best Term inhibitors has, ERK and p38 not on G-CSF induces the activation of JNK in a model of cell proliferation. Sun nnte k The combined treatment with MAP kinase and PI3K inhibitors Dienogest allow reduced doses of these inhibitors compared to medication alone. The peripheral administration of cytokines such as G-CSF and other mediators of inflammation-induced mechanical hyperalgesia depends h Of the vertebra Column and MAP kinase, PI3K. Therefore, it is conceivable that peripheral nociceptive mediators in response to acetic Acid produced, and formaldehyde PBQ w.