ReviewCurrent opinion in pharmacology2012
Analgesia by inhibiting tetrahydrobiopterin synthesis.
Review in Current opinion in pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration.Biomedicines · 2025Review
- Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Overexpression of miR-133a-3p reduces microglia activation by binding to GCH1, alleviating neuroinflammation and neuropathic pain.Experimental brain research · 2024Article
- Article
- Exploring the differences in serum metabolite profiles after intake of red meat in women with rheumatoid arthritis and a matched control group.European journal of nutrition · 2024Article
- 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
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry.Current neuropharmacology · 2021Review
- Turning liabilities into opportunities: Off-target based drug repurposing in cancer.Seminars in cancer biology · 2021Review
- Sepiapterin Reductase Inhibition Leading to Selective Reduction of Inflammatory Joint Pain in Mice and Increased Urinary Sepiapterin Levels in Humans and Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- Genetics of perioperative pain management.Current opinion in anaesthesiology · 2018Review
- Genetic variants of GCH1 associate with chronic and acute crisis pain in African Americans with sickle cell disease.Experimental hematology · 2018Article
- Combining Human and Rodent Genetics to Identify New Analgesics.Neuroscience bulletin · 2018Review
- Assessment of Chronic Pain: Domains, Methods, and Mechanisms.The journal of pain · 2016Review
- Tetrahydrobiopterin Biosynthesis as a Potential Target of the Kynurenine Pathway Metabolite Xanthurenic Acid.The Journal of biological chemistry · 2016Article
- Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.PloS one · 2016Article
- Effect of sulfasalazine on human neuroblastoma: analysis of sepiapterin reductase (SPR) as a new therapeutic target.BMC cancer · 2015Article
- Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway.Neuron · 2015Article
- A requirement for Gch1 and tetrahydrobiopterin in embryonic development.Developmental biology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Physiological control of the co-factor tetrahydrobiopterin (BH4) is tight in normal circumstances but levels increase pathologically in the injured somatosensory system. BH4 is an essential co-factor in the production of serotonin, dopamine, epinephrine, norepinephrine and nitric oxide. Excess BH4 levels cause pain, likely through excess production of one or more of these neurotransmitters or signaling molecules. The rate limiting step for BH4 production is GTP Cyclohydrolase 1 (GCH1). A human GCH1 gene haplotype exists that leads to less GCH1 transcription, translation, and therefore enzyme activity, following cellular stress. Carriers of this haplotype produce less BH4 and therefore feel less pain, especially following nerve injury where BH4 production is pathologically augmented. Sulfasalazine (SSZ) an FDA approved anti-inflammatory agent of unknown mechanism of action, has recently been shown to be a sepiapterin reductase (SPR) inhibitor. SPR is part of the BH4 synthesis cascade and is also upregulated by nerve injury. Inhibiting SPR will reduce BH4 levels and therefore should act as an analgesic. We propose SSZ as a novel anti-neuropathic pain medicine.
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.