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April 26, 2026Cureus0 citationsOpen Access

Gatekeepers of Pain: A Scoping Review on How Nanoparticle Engineering Illuminates Selective Transient Receptor Potential Vanilloid 1 (TRPV1) Targeting

AXAlexa Q. XiangThe Ohio State UniversityECEmily ChoWashington Hospital Healthcare SystemTJTiffany Jiang

Key Points

  • This review analyzes trends in nanoparticle delivery systems targeting TRPV1 for chronic pain therapy. It investigates how engineering these nanoparticles can enhance pain relief while minimizing side effects.
  • Performed a scoping review following PRISMA 2018 guidelines
  • Analyzed 100 top-cited records from Web of Science for bibliometric patterns
  • Synthesized qualitative data on nanoparticle systems and their mechanisms
  • Advanced nanoparticles showed ability to cross the blood-brain barrier and selectively modulate TRPV1 pathways.
  • Capsaicinoid-loaded nanoparticles improved bioavailability and decreased neuroinflammation compared to free capsaicin.
  • Sustained low-dose nanoparticle delivery led to analgesia, while high-dose caused neuronal ablation.

Abstract

Conventional analgesics often provide limited relief for chronic pain and can cause systemic side effects. This scoping review aims to analyze mechanistic and bibliometric trends in nanoparticle-engineered delivery systems designed to selectively modulate transient receptor potential vanilloid 1 (TRPV1) receptors for precision chronic pain therapy; following PRISMA 2018 guidelines, the first 100 top-cited records from the Web of Science (WoS) Core Collection were organized in Microsoft Excel (Microsoft® Corp., Redmond, WA) and BibTeX (Oren Patashnik, Stanford University, Stanford, CA) for bibliometric analysis, with data also being qualitatively synthesized. Citation patterns were concentrated among a few leading researchers and institutions, highlighting the value of aligning with established funding bodies. Advanced polymeric and magnetic nanoparticles demonstrated the ability to cross the blood-brain barrier and selectively modulate TRPV1-mediated pain pathways. Nanoparticles carrying charged capsaicinoids improved bioavailability and reduced neuroinflammation relative to free capsaicin. Dose-dependent effects were consistently observed, as sustained low-dose release produced receptor desensitization and analgesia, while burst or high-dose delivery caused neuronal ablation. Surface-functionalized nanoparticles, particularly those with TRPV1-binding ligands or redox-responsive coatings, enhanced receptor specificity and reduced transient receptor potential ankyrin 1 (TRPA1) co-activation. Rationally engineered nanoparticles optimized for size, charge, ligand density, and release kinetics present a promising avenue for safer, more effective chronic pain therapies. By selectively modulating TRPV1 while mitigating thermoregulatory disruption, researchers can achieve long-lasting analgesia by prioritizing targeting precision to advance sustainable chronic pain treatments.

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Cite This Study

Xiang et al. (2026) studied this question.

synapsesocial.com/papers/69edaafc4a46254e215b345dhttps://doi.org/10.7759/cureus.107610
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