ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Activation of TRPV1 mediates calcitonin gene-related peptide release, which excites trigeminal sensory neurons and is attenuated by a retargeted botulinum toxin with anti-nociceptive potential.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
127 citing papers in PubMed, 2 syntheses or guidelines pooled it, 245 citations in OpenAlex.
- Pooled it
- Pooled it
- Clinical efficacy of escitalopram combined with botulinum toxin A in patients with generalized anxiety disorder and comorbid headache.Psychopharmacology · 2023Trial
- Incobotulinum Toxin-A Improves Post-Surgical and Post-Radiation Pain in Cancer Patients.Toxins · 2016Trial
- Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia: observation of therapeutic effect from a randomized, double-blind, placebo-controlled trial.The journal of headache and pain · 2014Trial
- Botulinum toxin-type A: could it be an effective treatment option in intractable trigeminal neuralgia?The journal of headache and pain · 2013Trial
- [Botulinum toxin type A in the prophylactic treatment of chronic migraine].Schmerz (Berlin, Germany) · 2011Trial
- TRPV1-expressing neurons are dispensable for photophobia: evidence from a novel mouse light sensitivity assay.bioRxiv : the preprint server for biology · 2026Article
- Botulinum toxin type A attenuates trigeminal neuralgia-like pain by suppressing CGRP release and modulating NaV1.7-associated signaling.The journal of headache and pain · 2026Article
- Spinal nociceptive denervation impedes subsequent chronic autonomic remodeling after myocardial infarction in male swine.Nature communications · 2026Article
- Laser-Based Photobiomodulation for Orthodontic Pain: Mechanistic Evidence from Experimental Tooth-Movement Models.International journal of molecular sciences · 2026Review
- Design and Characterization of Recombinant and Chimeric BoNT/A Neurotoxins with Receptor-Binding Domain Grafting.Toxins · 2026Article
- Cholera Toxin-Mediated Targeting of Botulinum Neurotoxin Activity to Pain-Associated Sensory Neurons.Toxins · 2026Article
- Common themes in evoked ion channel translocation in neuroplastic and homeostatic plasticity.Frontiers in pharmacology · 2026Review
- Perineural Administration of Botulinum Toxin for Chronic Pain Management: A Narrative Review.Pain research & management · 2026Review
- Redefining Chemotherapy-Related Headaches: From Pathobiology to Differential Diagnosis and Management.International journal of molecular sciences · 2025Review
- Suzetrigine, a Non-Opioid Small-Molecule Analgesic: Mechanism of Action, Clinical, and Translational Science.Clinical and translational science · 2025Review
- Structural and molecular differentiation of cultured human neurons is accompanied by alterations of spontaneous and evoked calcium dynamics.Scientific reports · 2025Article
- Review
- Can Botulinum Toxin Type E Serve as a Novel Therapeutic Target for Managing Chronic Orofacial Pain?Toxins · 2025Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive release of inflammatory/pain mediators from peripheral sensory afferents renders nerve endings hyper-responsive, causing central sensitization and chronic pain. Herein, the basal release of proinflammatory calcitonin gene-related peptide (CGRP) was shown to increase the excitability of trigeminal sensory neurons in brainstem slices via CGRP1 receptors because the effect was negated by an antagonist, CGRP8-37. This excitatory action could be prevented by cleaving synaptosomal-associated protein of M(r) 25,000 (SNAP-25) with botulinum neurotoxin (BoNT) type A, a potent inhibitor of exocytosis. Strikingly, BoNT/A proved unable to abolish the CGRP1 receptor-mediated effect of capsaicin, a nociceptive TRPV1 stimulant, or its elevation of CGRP release from trigeminal ganglionic neurons (TGNs) in culture. Although the latter was also not susceptible to BoNT/E, apparently attributable to a paucity of its acceptors (glycosylated synaptic vesicle protein 2 A/B), this was overcome by using a recombinant chimera (EA) of BoNT/A and BoNT/E. It bound effectively to the C isoform of SV2 abundantly expressed in TGNs and cleaved SNAP-25, indicating that its /A binding domain (H(C)) mediated uptake of the active /E protease. The efficacy of /EA is attributable to removal of 26 C-terminal residues from SNAP-25, precluding formation of SDS-resistant SNARE complexes. In contrast, exocytosis could be evoked after deleting nine of the SNAP-25 residues with /A but only on prolonged elevation of [Ca(2+)](i) with capsaicin. This successful targeting of /EA to nociceptive neurons and inhibition of CGRP release in vitro and in situ highlight its potential as a new therapy for sensory dysmodulation and chronic pain.
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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.