ArticleNeurobiology of disease2014
Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 106 citations in OpenAlex.
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- Quinoline-Based Neuropilin‑1 Antagonists Exhibit a Pure Antagonist Profile and Block Vascular Endothelial Growth Factor-Induced Pain.ACS pharmacology & translational science · 2025Article
- Epigenetic modifications associated to diabetic peripheral neuropathic pain (Review).Molecular medicine reports · 2025Review
- Paclitaxel alters the microvascular network in the central and peripheral nervous system of rats with chemotherapy-induced painful peripheral neuropathy.Journal of the peripheral nervous system : JPNS · 2024Article
- Early-life cisplatin exposure induces neuroinflammation and chemotherapy-induced neuropathic pain.Disease models & mechanisms · 2024Article
- Postsynaptic lncRNA Sera/Pkm2 pathway orchestrates the transition from social competition to rank by remodeling the neural ensemble in mPFC.Cell discovery · 2024Article
- Elevated cytokine levels in the central nervous system of cluster headache patients in bout and in remission.The journal of headache and pain · 2024Article
- RNA isoform expression landscape of the human dorsal root ganglion (DRG) generated from long read sequencing.bioRxiv : the preprint server for biology · 2023Article
- Vascular endothelial growth factor isoforms differentially protect neurons against neurotoxic events associated with Alzheimer's disease.Frontiers in molecular neuroscience · 2023Article
- The VEGF/VEGFR Axis Revisited: Implications for Cancer Therapy.International journal of molecular sciences · 2022Review
- Interplay between cellular changes in the knee joint, circulating lipids and pain behaviours in a slowly progressing murine model of osteoarthritis.European journal of pain (London, England) · 2022Article
- Clinical and Preclinical Evidence for Roles of Soluble Epoxide Hydrolase in Osteoarthritis Knee Pain.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Targeting Vascular endothelial growth factor A with soluble vascular endothelial growth factor receptor 1 ameliorates nerve injury-induced neuropathic pain.Molecular pain · 2022Article
- Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise.International journal of environmental research and public health · 2021Review
- VEGF-A/VEGFR-1 signalling and chemotherapy-induced neuropathic pain: therapeutic potential of a novel anti-VEGFR-1 monoclonal antibody.Journal of experimental & clinical cancer research : CR · 2021Article
- Stem cells from human exfoliated deciduous teeth attenuate mechanical allodynia in mice through distinct from the siglec-9/MCP-1-mediated tissue-repairing mechanism.Scientific reports · 2021Article
- USP39 promotes malignant proliferation and angiogenesis of renal cell carcinoma by inhibiting VEGF-ACancer cell international · 2021Article
- Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry.ACS chemical neuroscience · 2021Article
- SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia.Pain · 2021Article
- Downregulation of long noncoding RNA DLEU1 attenuates hypersensitivity in chronic constriction injury-induced neuropathic pain in rats by targeting miR-133a-3p/SRPK1 axis.Molecular medicine (Cambridge, Mass.) · 2020Article
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Vascular endothelial growth factor-A (VEGF-A) is best known as a key regulator of the formation of new blood vessels. Neutralization of VEGF-A with anti-VEGF therapy e.g. bevacizumab, can be painful, and this is hypothesized to result from a loss of VEGF-A-mediated neuroprotection. The multiple vegf-a gene products consist of two alternatively spliced families, typified by VEGF-A165a and VEGF-A165b (both contain 165 amino acids), both of which are neuroprotective. Under pathological conditions, such as in inflammation and cancer, the pro-angiogenic VEGF-A165a is upregulated and predominates over the VEGF-A165b isoform. We show here that in rats and mice VEGF-A165a and VEGF-A165b have opposing effects on pain, and that blocking the proximal splicing event - leading to the preferential expression of VEGF-A165b over VEGF165a - prevents pain in vivo. VEGF-A165a sensitizes peripheral nociceptive neurons through actions on VEGFR2 and a TRPV1-dependent mechanism, thus enhancing nociceptive signaling. VEGF-A165b blocks the effect of VEGF-A165a. After nerve injury, the endogenous balance of VEGF-A isoforms switches to greater expression of VEGF-Axxxa compared to VEGF-Axxxb, through an SRPK1-dependent pre-mRNA splicing mechanism. Pharmacological inhibition of SRPK1 after traumatic nerve injury selectively reduced VEGF-Axxxa expression and reversed associated neuropathic pain. Exogenous VEGF-A165b also ameliorated neuropathic pain. We conclude that the relative levels of alternatively spliced VEGF-A isoforms are critical for pain modulation under both normal conditions and in sensory neuropathy. Altering VEGF-Axxxa/VEGF-Axxxb balance by targeting alternative RNA splicing may be a new analgesic strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.