Figure 6.

Role of VEGFR1 in Pain Associated with PDAC

(A and B) Examples (A) and quantitative analyses (B) of nerves (arrows) showing anti-VEGFR1 immunoreactivity in PDAC biopsies from patients. Arrowheads indicate blood vessels. n = 21 sections analyzed from 13 biopsies.

(C and D) Typical examples (C) and quantitative summary (D) of VEGFR1 expression in PGP9.5-positive nerves in human PDAC and pancreas of healthy donors (n = 95 sections from 30 patients and 7 donors).

(E and F) Typical examples (E) and quantitative summary (F) of the relation between VEGFR1 immunoreactivity in human PDAC biopsies and subjective pain rating reported by the patients (n = 79 sections from 30 patients).

(G) Western blot analysis of VEGFR1 expression in DRGs of mice with Advillin-Cre-mediated pan-DRG VEGFR1 deletion (Adv-Vegfr1^−/−) and controls (Vegfr1^fl/fl).

(H) VEGF-A-induced mechanical hypersensitivity (left) and thermal hyperalgesia (right) in Adv-Vegfr1^−/− and Vegfr1^fl/fl mice (n = at least 4 mice/group).

(I and J) Comparison of early post-operative pain (red arrow), tumor-associated hypersensitivity (blue arrow) to 0.008 g of abdominal von Frey application (I) and integral of responses to all von Frey forces tested (right) and tumor mass (J) between Adv-Vegfr1^−/− mice, SNS-Vegfr1^−/− mice, and Vegfr1^fl/fl mice (n = at least 8 mice/group).

^∗p < 0.05, t test in (D) and (F). ^∗p < 0.05 as compared with basal in (H) and (I); ANOVA for repeated-measures followed post hoc Fisher’s test; ^†p < 0.05 as compared with corresponding control group, ANOVA for random measures followed by post hoc Fisher’s test. Scale bar represents 100 μm in (A) and (C) and 50 μm in (E). Data are presented as mean ± SEM. See also Figure S5.