ArticleProceedings of the National Academy of Sciences of the United States of America2014
αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Targeting TRPV1 channels: new perspectives on the mechanisms of analgesia for herpes zoster neuralgia and advances in therapeutic research.Frontiers in cellular and infection microbiology · 2026Pooled it
- Trial
- Small peptides derived from the autoinhibitory XY linker of phospholipase C-β isoforms inhibit enzyme activity and reduce inflammation.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Pathophysiological mechanisms of benign prostatic obstruction in men with small prostate volume and the emerging role of ultra-minimally invasive prostatic urethral dilation: a narrative review.Frontiers in molecular biosciences · 2026Review
- Capsaicin for cardiometabolic syndrome: multitarget mechanisms and therapeutic potential.Frontiers in nutrition · 2026Review
- Morphological Correlates of TRPV1 Agonist-Induced Activation and Defunctionalization of Nociceptor Neurons.International journal of molecular sciences · 2025Review
- Protective role of TRPV1Brain, behavior, & immunity - health · 2024Article
- Thoracic Dorsal Root Ganglion Application of Resiniferatoxin Reduces Myocardial Ischemia-Induced Ventricular Arrhythmias.Biomedicines · 2023Article
- Osmotically evoked PLCδ1-dependent translocation of ΔN-TRPV1 channels in rat supraoptic neurons.iScience · 2023Article
- Bipartite Activation of Sensory Neurons by a TRPA1 Agonist Allyl Isothiocyanate Is Reflected by Complex CaInternational journal of molecular sciences · 2023Article
- Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety.Frontiers in pharmacology · 2023Article
- A compendium of validated pain genes.WIREs mechanisms of disease · 2022Review
- TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine.Nature communications · 2022Article
- NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases.International journal of molecular sciences · 2022Article
- TRPV1 in chronic pruritus and pain: Soft modulation as a therapeutic strategy.Frontiers in molecular neuroscience · 2022Review
- 17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats.International journal of molecular sciences · 2021Article
- CaInternational journal of molecular sciences · 2021Article
- Dietary capsaicin normalizes CGRP peptidergic DRG neurons in experimental diabetic peripheral neuropathy.Scientific reports · 2021Article
- A capsaicinoid-based soft drug, AG1529, for attenuating TRPV1-mediated histaminergic and inflammatory sensory neuron excitability.Scientific reports · 2021Article
- Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proalgesic sensitization of peripheral nociceptors in painful syndromes is a complex molecular process poorly understood that involves mobilization of thermosensory receptors to the neuronal surface. However, whether recruitment of vesicular thermoTRP channels is a general mechanism underlying sensitization of all nociceptor types or is subtype-specific remains controversial. We report that sensitization-induced Ca(2+)-dependent exocytotic insertion of transient receptor potential vanilloid 1 (TRPV1) receptors to the neuronal plasma membrane is a mechanism specifically used by peptidergic nociceptors to potentiate their excitability. Notably, we found that TRPV1 is present in large dense-core vesicles (LDCVs) that were mobilized to the neuronal surface in response to a sensitizing insult. Deletion or silencing of calcitonin-gene-related peptide alpha (αCGRP) gene expression drastically reduced proalgesic TRPV1 potentiation in peptidergic nociceptors by abrogating its Ca(2+)-dependent exocytotic recruitment. These findings uncover a context-dependent molecular mechanism of TRPV1 algesic sensitization and a previously unrecognized role of αCGRP in LDCV mobilization in peptidergic nociceptors. Furthermore, these results imply that concurrent secretion of neuropeptides and channels in peptidergic C-type nociceptors facilitates a rapid modulation of pain signaling.
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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 OpenQuestion graph.