ArticleNature communications2023
Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 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
- An Extracellular Pore‑Targeting Peptide Defines a Designable Allosteric Site in TRPV2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular target for neuroinflammation and pain management: transient receptor potential vanilloid 1.Inflammopharmacology · 2026Review
- Distinct Role of Specialized Cutaneous Schwann Cell Network in Acute and Chronic Pain Sensation.Neuroscience bulletin · 2026Article
- Calpain cleaves the distal carboxyl terminus of TRPV1 and modulates its tachyphylaxis.Cell & bioscience · 2026Article
- Review
- From Discovery to the Future Medical Applications of Venom-derived Analgesic Peptides for the Treatment of Peripheral Pains.Current pharmaceutical design · 2026Review
- Intraepidermal Nerve Fiber Quantification of the Mouse Hind Paw Footpads: A Detailed and Simplified Protocol.Bio-protocol · 2025Article
- Mechanism of capsaicin entry into buried vanilloid sites in TRPV1.Nature chemical biology · 2025Article
- Andrographolide potentiates anti-tumor immunity in colorectal cancer (CRC) by targeting voltage-dependent anion channel (VDAC) and activating the cGAS-STING axis.Journal of gastrointestinal oncology · 2025Article
- Possible Anti-Pain Vaccines: A Narrative Review of Emerging Strategies and Clinical Prospects.Vaccines · 2025Review
- The Endocannabinoid Peptide RVD-Hemopressin Is a TRPV1 Channel Blocker.Biomolecules · 2024Article
- Exploring oak processionary caterpillar induced lepidopterism (part 2): ex vivo bio-assays unmask the role of TRPV1.Cellular and molecular life sciences : CMLS · 2024Article
- Design, synthesis and functional validation of peptide inhibitors based on TRPV1 ion channel agonist RhTx.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Article
- Structural insights into ion selectivity and transport mechanisms of Oryza sativa HKT2;1 and HKT2;2/1 transporters.Nature plants · 2024Article
- Molecular engineering of AIE-active boron clustoluminogens for enhanced boron neutron capture therapy.Chemical science · 2024Article
- A new polymodal gating model of the proton-activated chloride channel.PLoS biology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential vanilloid 1 (TRPV1) ion channel is a classic analgesic target, but antagonists of TRPV1 failed in clinical trials due to their side effects like hyperthermia. Here we rationally engineer a peptide s-RhTx as a positive allosteric modulator (PAM) of TRPV1. Patch-clamp recordings demonstrate s-RhTx selectively potentiated TRPV1 activation. s-RhTx also slows down capsaicin-induced desensitization of TRPV1 in the presence of calcium to cause more calcium influx in TRPV1-expressing cells. In addition, our thermodynamic mutant cycle analysis shows that E652 in TRPV1 outer pore specifically interacts with R12 and K22 in s-RhTx. Furthermore, we demonstrate in vivo that s-RhTx exhibits long-lasting analgesic effects in noxious heat hyperalgesia and CFA-induced chronic inflammatory pain by promoting the reversible degeneration of intra-epidermal nerve fiber (IENF) expressing TRPV1 channels in mice, while their body temperature remains unaffected. Our results suggest s-RhTx is an analgesic agent as a PAM of TRPV1.
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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.