A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain
نویسندگان
چکیده
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.
منابع مشابه
miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels
Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs (miRNAs) are a class of noncoding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for miRNAs regulated in dorsal root ganglia (DRG) neurons in a mouse model of bone metastatic pain, we identified miR-34c-5p as a functionally important pronociceptive miRNA. Desp...
متن کاملO-28: Role of HOX Family Related Genes in Pain Generation of Endometriosis Patients
Background Endometriosis is a common gynecological disease, can cause severe pelvic pain. Studies demonstrated the presence of sensory nerve fibers in endometrium of endometriosis patient. Nevertheless, no information is available on mechanisms of sensory nerve formation in eutopic or ectopic lesions. Since HOX genes have important roles in both reproductive tract and nerve growth, we decided t...
متن کاملWnt-Fzd Signaling Sensitizes Peripheral Sensory Neurons via Distinct Noncanonical Pathways
Wnt signaling represents a highly versatile signaling system, which plays diverse and critical roles in various aspects of neural development. Sensory neurons of the dorsal root ganglia require Wnt signaling for initial cell-fate determination as well as patterning and synapse formation. Here we report that Wnt signaling pathways persist in adult sensory neurons and play a functional role in th...
متن کاملMorphological Identification of Cell Death in Dorsal Root Ganglion Neurons Following Peripheral Nerve injury and repair in adult rat
Background: Axotomy causes sensory neuronal loss. Reconnection of proximal and distal nerve ends by surgical repair improves neuronal survival. It is important to know the morphology of primary sensory neurons after the surgical repair of their peripheral processes. Methods: Animals (male Wistar rats) were exposed to models of sciatic nerve transection, direct epineurial suture repair of sciati...
متن کاملChanges in functional properties of A-type but not C-type sensory neurons in vivo in a rat model of peripheral neuropathy
BACKGROUND The aim of this study was to compare primary sensory neurons in controls and in an animal neuropathic pain model in order to understand which types of neurons undergo changes associated with peripheral neuropathy. On the basis of intracellular recordings in vivo from somata, L4 sensory dorsal root ganglion neurons were categorized according to action potential configuration, conducti...
متن کامل