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Inhibition of VEGF receptor 2 signaling in the spinal cord attenuated behavioral nociceptive responses to mechanical, heat and formalin stimuli, indicating that spinal VEGF receptor 2 activation has potent pro nociceptive actions. Furthermore, intrathecal VEGF A165a resulted in mechanical and heat hyperalgesia, whereas the sister inhibitory isoform VEGF A165b resulted in anti nociception. These results support a role for myelinated fiber pathways, and alternative pre mRNA splicing of factors such as VEGF A in the spinal processing of neuropathic pain.

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