ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2025
Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed.
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- Recent advances in nanomaterial-based strategies for chronic pain alleviation.Materials today. Bio · 2026Review
- The Janus face of CaMKII: from memory consolidation to neurotoxic switch in Alzheimer's disease.Archives of toxicology · 2025Review
- From a clinically relevant pain target to a possible analgesic treatment strategy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tetrahydrobiopterin (BH4) expression is normally strictly controlled; however, its intracellular levels increase considerably following nerve damage. GTP cyclohydrolase I (GCH1) plays a crucial role in regulating BH4 concentration, with an upregulation observed in the dorsal root ganglion in cases of neuropathic pain. In this study, we aimed to develop and evaluate the clinical potential of an RNA interference-based adeno-associated virus (AAV) targeting GCH1 across various species to decrease BH4 levels and, consequently, alleviate neuropathic pain symptoms. We identified universal small-interfering RNA sequences effective across species and developed an AAV-u-shRNA that successfully suppressed GCH1 expression with minimal off-target effects. Male Sprague Dawley rats were divided into four groups: normal, spared nerve injury, AAV-shCON, and AAV-u-shGCH1. The rats were sacrificed on post-injection day 28 to collect blood for BH4 level assessment. The AAV-u-shGCH1 group demonstrated remarkable improvement in the mechanical withdrawal threshold by PID 28, significantly outperforming the normal, spared nerve injury, and AAV-shCON groups. Plasma BH4 levels confirmed that AAV-u-shGCH1 effectively reduced neuropathic pain by inhibiting BH4 synthesis in vivo, introducing a novel, multispecies-compatible therapeutic strategy. Our results suggest that a single application of AAV-u-shGCH1 could offer a viable solution for neuropathic pain relief.
Indexed as
Identifiers
What OpenQuestion holds
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.