ReviewCurrent pharmaceutical biotechnology2011
GCH1, BH4 and pain.
Review in Current pharmaceutical biotechnology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 70 citations in OpenAlex.
- Alterations in biopterin metabolism and the effects of tetrahydrobiopterin supplementation in a rat model of short bowel syndrome.Pediatric surgery international · 2026Article
- Research progress of ferroptosis in obesity and its complications.Journal of physiology and biochemistry · 2026Review
- BH4 Oxidation-Derived HJournal of neurochemistry · 2025Article
- Modeling Pain Without Injury: Inherited Rodent Models as Mechanistic Windows into Chronic Pain.Function (Oxford, England) · 2025Review
- Mitochondrial Gene Regulation and Pain Susceptibility: A Multi-Omics Causal Inference Study.International journal of molecular sciences · 2025Article
- High-Resolution Whole-Genome DNA Methylation Revealed Unique Signatures of Painful Diabetic Neuropathy.Diabetes · 2025Article
- Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- RNA Interference Unleashed: Current Perspective of Small Interfering RNA (siRNA) Therapeutics in the Treatment of Neuropathic Pain.ACS pharmacology & translational science · 2024Review
- Epigenetic regulation of targeted ferroptosis: A new strategy for drug development.Journal of pharmaceutical analysis · 2024Review
- Research progress on ferroptosis in colorectal cancer.Frontiers in immunology · 2024Review
- Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Artificial Neural Networks Coupled with MALDI-TOF MS Serum Fingerprinting To Classify and Diagnose Pathological Pain Subtypes in Preclinical Models.ACS chemical neuroscience · 2023Article
- In Silico Investigation of the Human GTP Cyclohydrolase 1 Enzyme Reveals the Potential of Drug Repurposing Approaches towards the Discovery of Effective BHInternational journal of molecular sciences · 2023Article
- Crosstalk between ferroptosis and steroid hormone signaling in gynecologic cancers.Frontiers in molecular biosciences · 2023Review
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- Pathways Activated by Infected and Bystander Chondrocytes in Response to Ross River Virus Infection.Viruses · 2022Article
- GPX4-independent ferroptosis-a new strategy in disease's therapy.Cell death discovery · 2022Review
- The Identification of Blood Biomarkers of Chronic Neuropathic Pain by Comparative Transcriptomics.Neuromolecular medicine · 2022Article
- Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer.Science translational medicine · 2022Article
- The critical role and molecular mechanisms of ferroptosis in antioxidant systems: a narrative review.Annals of translational medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Understanding and consequently treating neuropathic pain effectively is a challenge for modern medicine, as unlike inflammation, which can be controlled relatively well, chronic pain due to nerve injury is refractory to most current therapeutics. Here we define a target pathway for a new class of analgesics, tetrahydrobiopterin (BH4) synthesis and metabolism. BH4 is an essential co-factor in the synthesis of serotonin, dopamine, epinephrine, norepinephrine and nitric oxide and as a result, its availability influences many systems, including neurons. Following peripheral nerve damage, levels of BH4 are dramatically increased in sensory neurons, consequently this has a profound effect on the physiology of these cells, causing increased activity and pain hypersensitivity. These changes are principally due to the upregulation of the rate limiting enzyme for BH4 synthesis GTP Cyclohydrolase 1 (GCH1). A GCH1 pain-protective haplotype which decreases pain levels in a variety of settings, by reducing the levels of endogenous activation of this enzyme, has been characterized in humans. Here we define the control of BH4 homeostasis and discuss the consequences of large perturbations within this system, both negatively via genetic mutations and after pathological increases in the production of this cofactor that result in chronic pain. We explain the nature of the GCH1 reduced-function haplotype and set out the potential for a ' BH4 blocking' drug as a novel analgesic.
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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.