Figure 8.

Effects of Local or Systemic Immunological Blockade of VEGFR1 or VEGFR2 on Cancer Pain

(A and B) Effects of a regime of local, intraplantar injections of either IgG or anti-VEGFR1 or anti-VEGFR2 antibodies (5 μg/dose) on tumor-induced mechanical hypersensitivity (A) and tumor-induced hypertrophy and sprouting of PGP9.5-immunoreactive epidermal sensory nerves (B) in the calcaneus osteolytic sarcoma implantation model (n = at least 6 mice/group).

(C–E) Analysis of tumor-induced mechanical hypersensitivity in the ipsilateral mouse paw (C), spontaneous pain (D), and sprouting of the femur periosteal peptidergic nociceptive fibers (E) induced by implantation of mammary cancer cells in the mouse femur bone in mice receiving a regime of systemic injections of either control IgG or the VEGFR1-neutralizing MF-1 clone or the VEGFR2-neutralizing DC101 clone (40 mg/kg body weight per injection, n = 8 mice/group).

In all panels, ^∗p < 0.05 as compared with basal; ANOVA of repeated-measures, ^†p < 0.05 as compared with control IgG, ^#p < 0.01 as compared with sham; only in (D), p < 0.05 between MF-1 and DC101 groups is indicated by $ sign; ANOVA followed by post hoc Fisher’s test. Scale bars represent 50 μm and 25 μm in (B) and (E), respectively. Data are presented as mean ± SEM. See also Figure S7 and Movies S1, S2, S3, and S4.