A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain.
Bottom Line: Cancer pain is a debilitating disorder and a primary determinant of the poor quality of life.Here, we report a non-vascular role for ligands of the Vascular Endothelial Growth Factor (VEGF) family in cancer pain.These findings identify a therapeutic potential for VEGFR1-modifying drugs in cancer pain and suggest a palliative effect for VEGF/VEGFR1-targeting anti-angiogenic tumor therapies.
Affiliation: Pharmacology Institute, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.Show MeSH
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Mentions: To further obtain evidence from genetic models and to specifically delineate the contribution of VEGFR1 expressed in nociceptive neurons of the DRG, we generated a line of transgenic mice conditionally lacking VEGFR1 in nociceptive neurons by mating Vegfr1fl/fl mice (Ambati et al., 2006) with SNS-Cre mice (Agarwal et al., 2004) (SNS-Vegfr1−/− mice). Western blot analysis (Figure 5A) confirmed a decrease in DRG expression of VEGFR1 (55% ± 2.8% of the value in Vegfr1fl/fl mice). Intraplantar VEGF-A-induced mechanical and thermal hypersensitivity was nearly entirely lost in SNS-Vegfr1−/− mice as compared with their WT littermates, indicating a requirement for VEGFR1 expressed in peripheral nociceptors (Figures 5B and 5C).
Affiliation: Pharmacology Institute, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.