Lture responsive to an increased HTES level Hedgehog Pathway of TGF an intracellular Other proteins in cells. These data are consistent with the results of the ELISA and RT-PCR analysis. HG increased Mpft hte ERK1 / 2, but steamed STAT3 phosphorylation in MAPC Western blot analysis was performed, determine the total and phosphorylated ERK1 / 2 and STAT3 in MAPC. Detectable concentrations of two ERK1 / 2 and STAT3 phosphorylation in cells were grown in normal conditions were observed. The phosphorylation of ERK1 / 2 remained in cells which changed without 20 mM glucose as L in a normal state. Interestingly, the phosphorylation of ERK1 / 2 fa erh Ht Is clearly more than 3 times in contr MAPC after 36 h of culture in the medium compared to HG L. In contrast, STAT3 phosphorylation was raised slightly to 30% in cells in high osmolarity medium T erh Ht with 20 mM glucose L. However, phospho STAT3 level was significantly decreased by about 90% after 36 h of N MAPC Culture media in HG compared to contr One, which was consistent with our previous observations. Interestingly, the effect of HG on ERK1 / 2 and STAT3 was Transient Dependent. As shown in Fig. 2C and D, supply changes In the ERK1 / 2 and STAT3 induced by HG are no longer present in the cells after 48 h culture in HG media. Both ERK1 / 2 and STAT3 also MAPCs in normal or in the press or media HG were activated grown. Interestingly, the phosphorylation of STAT3 level was slightly increased in HG-cells after 36 h of culture Ht, then back to normal after 48 h, suggesting that the effect of HG on STAT3 phosphorylation was specific residue. To determine whether a Hnlicher effect of HG was on ERK1 / 2 and STAT3 in other cells, human endothelial cells were cultured in HG media. It was found that HG fa ht obtained STAT3 phosphorylation is significantly more than 2-fold after 36 h of contr culture compared HAECs L, w While no Ver Change of ERK1 / 2 and the activation of Akt were observed. These data suggest that HG-induced inhibition of STAT3 phosphorylation and the improvement of the ERK1 / 2 signaling pathway was specific to MAPC. Improvement of ERK1 / 2 signaling pathway leads to inhibition of STAT3 phosphorylation in a state of HG as in Figure 2A and B, which activates both ERK1 / 2 and STAT3 in MAPC under normal conditions. However, HG significantly enhanced ERK1 / 2 phosphorylation, w While STAT3 phosphorylationTNF acting IL-1 and chemokines synergistically to induce the writhing response. These cytokines act synergistically in the injection of a pool of cytokines t satisfied that the injection of a cytokine induced wall insulated, w While it decreases the response of these cytokines vinegar Acid-induced reaction wall. However, the size is E / Number winds through the injection of a pool of cytokines significantly lower than that in vinegar Acid-induced, suggesting the involvement of other nociceptive pathways. Actually act, and cyclooxygenase products cysteinyl leukotrienes and nociception in this model. The wall reaction of acetic acid in the model Reduced by treatment with opio Of the cyclooxygenase inhibitors, and a plurality of natural products. The model has a pharmacological profile PBQ although there are some differences in the mechanisms. For example, the PBQ, but not the acetic Acid wall dependent Independent cytokines such as IL.