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A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain.

ABSTRACT: 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. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented tumor-induced nerve remodeling and attenuated cancer pain in diverse mouse models in vivo. 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.

SUBMITTER: Selvaraj D

PROVIDER: S-EPMC4469373 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain.

Selvaraj Deepitha D Gangadharan Vijayan V Michalski Christoph W CW Kurejova Martina M Stösser Sebastian S Srivastava Kshitij K Schweizerhof Matthias M Waltenberger Johannes J Ferrara Napoleone N Heppenstall Paul P Shibuya Masabumi M Augustin Hellmut G HG Kuner Rohini R

Cancer cell 20150601 6

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. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented ...[more]

PMID: 26058077

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2022-11-17 | GSE187345 | GEO

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Selective conversion of fibroblasts into peripheral sensory neurons.

Project description:Humans and mice detect pain, itch, temperature, pressure, stretch and limb position via signaling from peripheral sensory neurons. These neurons are divided into three functional classes (nociceptors/pruritoceptors, mechanoreceptors and proprioceptors) that are distinguished by their selective expression of TrkA, TrkB or TrkC receptors, respectively. We found that transiently coexpressing Brn3a with either Ngn1 or Ngn2 selectively reprogrammed human and mouse fibroblasts to acquire key properties of these three classes of sensory neurons. These induced sensory neurons (iSNs) were electrically active, exhibited distinct sensory neuron morphologies and matched the characteristic gene expression patterns of endogenous sensory neurons, including selective expression of Trk receptors. In addition, we found that calcium-imaging assays could identify subsets of iSNs that selectively responded to diverse ligands known to activate itch- and pain-sensing neurons. These results offer a simple and rapid means for producing genetically diverse human sensory neurons suitable for drug screening and mechanistic studies.

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Peripheral glia have a pivotal role in the initial response to axon degeneration of peripheral sensory neurons in zebrafish.

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