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Figure 5 | Molecular Pain

Figure 5

From: Ret-dependent and Ret-independent mechanisms of Gfl-induced sensitization

Figure 5

GDNF-activates the MAPK pathway and not the PI-3K pathway and sensitizes sensory neurons through the MAPK pathway. A) This representative Western blot demonstrates changes in levels of p-Erk 1/2, Erk 1/2, p-Akt, Akt, and α-tubulin in DRG in response to a 10 minute incubation with 10 ng/mL GDNF and the subsequent prevention of these changes by inhibitors of the MAPK pathway (10 μM PD98059 and 1 μM U0126) and the PI-3K pathway (10 μM LY294002). B and C) Densitometric analysis of three separate Western blots like that in A probing for B) MAPK pathway components and C) PI-3K pathway components. D) Peptide release elicited by a 10 minute exposure to Hepes buffer alone (open bar) or Hepes buffer containing 50 nM capsaicin (Cap; dark bars) is expressed as mean percent total peptide content of cells in each well ± SEM (n = 12-18 wells per condition). GDNF and inhibitors.were included in the 10 minutes prior to and throughout capsaicin exposure. Asterisks (*) indicate statistically significant differences in band density and iCGRP release between treatment groups and the no GDNF condition using an ANOVA with Dunnett's post-hoc test (p < 0.05). Ampersands (@) indicate statistically significant differences between the 10 ng/mL treatment condition and the condition containing the inhibitor listed below the graph using t-tests (p < 0.05). In all cases, release stimulated by capsaicin was significantly higher than basal release.

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