INT150934

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Context Info
Confidence 0.78
First Reported 2007
Last Reported 2010
Negated 1
Speculated 2
Reported most in Body
Documents 17
Total Number 19
Disease Relevance 14.54
Pain Relevance 17.53

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (GCH1) small molecule metabolic process (GCH1) nucleolus (GCH1)
nucleus (GCH1) protein complex assembly (GCH1) protein complex (GCH1)
Anatomy Link Frequency
white blood cells 1
endothelium 1
GCH1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Pain 834 100.00 Very High Very High Very High
GCH1 184 100.00 Very High Very High Very High
Tetrahydrobiopterin 78 99.98 Very High Very High Very High
Chronic pancreatitis 102 99.92 Very High Very High Very High
Neuropathic pain 19 99.70 Very High Very High Very High
opioid receptor 14 99.36 Very High Very High Very High
Catecholamine 5 99.26 Very High Very High Very High
analgesia 16 99.08 Very High Very High Very High
Serotonin 7 98.88 Very High Very High Very High
Lasting pain 40 98.64 Very High Very High Very High
Disease Link Frequency Relevance Heat
Pain 874 100.00 Very High Very High Very High
Pancreatitis 193 99.92 Very High Very High Very High
Neuropathic Pain 40 99.70 Very High Very High Very High
Complex Regional Pain Syndromes 11 97.96 Very High Very High Very High
Dystonia 6 96.96 Very High Very High Very High
Inflammatory Pain 9 94.76 High High
Fibromyalgia 88 92.72 High High
Syndrome 16 92.24 High High
Irritable Bowel Syndrome /

Irritable Bowel Syndrome Super / Visceral Pain

21 91.84 High High
Somatoform Disorder 1 84.92 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The initial published report of GCH1 genotypes influencing clinical pain suggested that pain pathways sensitive to changes in GCH1 expression involve neuropathic pain [7], which may be uncommon in RAP or CP.
Gene_expression (expression) of GCH1 associated with pain, pancreatitis, neuropathic pain, gch1 and chronic pancreatitis
1) Confidence 0.78 Published 2008 Journal Mol Pain Section Body Doc Link PMC2626574 Disease Relevance 1.53 Pain Relevance 1.96
GCH1 expression was significantly increased in a rat model of peripheral neuropathic pain, and blocking GCH1 reduced the pain response [7].
Gene_expression (expression) of GCH1 associated with pain, neuropathic pain and gch1
2) Confidence 0.78 Published 2008 Journal Mol Pain Section Body Doc Link PMC2626574 Disease Relevance 1.60 Pain Relevance 2.03
GCH1, iNOS upregulation and BH4 production were assessed ex-vivo in white blood cells after lipopolysaccharide stimulation for 24 h.
Gene_expression (production) of GCH1 in white blood cells
3) Confidence 0.77 Published 2008 Journal Eur J Pain Section Body Doc Link 18374612 Disease Relevance 0.09 Pain Relevance 0
The single large 72 kb block identified by Tegeder et al for GCH1 with 168 Caucasian chronic lumbar root pain subjects is not consistent with the HapMap Caucasians (CEU), which may reflect a lack of generalizability for the Tegeder et al results.
Neg (not) Gene_expression (consistent) of GCH1 associated with pain and gch1
4) Confidence 0.68 Published 2007 Journal Mol Pain Section Body Doc Link PMC1821314 Disease Relevance 0.18 Pain Relevance 0.30
GCH1 expression was significantly increased in a rat model of peripheral neuropathic pain, and blocking GCH1 reduced the pain response [7].
Gene_expression (reduced) of GCH1 associated with pain, neuropathic pain and gch1
5) Confidence 0.67 Published 2008 Journal Mol Pain Section Body Doc Link PMC2626574 Disease Relevance 1.55 Pain Relevance 1.97
Genotyping was performed and three single nucleotide polymorphisms (SNP) previously defined as a pain-protective SNP combination of GCH1 were used.
Gene_expression (combination) of GCH1 associated with pain and gch1
6) Confidence 0.67 Published 2010 Journal Mol Pain Section Abstract Doc Link 20633294 Disease Relevance 0.19 Pain Relevance 0.39
Different SNP combinations in the GCH1 gene and use of labor analgesia.
Gene_expression (combinations) of GCH1 associated with gch1 and analgesia
7) Confidence 0.67 Published 2010 Journal Mol Pain Section Title Doc Link 20633294 Disease Relevance 0.09 Pain Relevance 0.41
Reducing the elevated BH4 levels associated with pain to baseline, while maintaining sufficient BH4 levels to limit side effects is the goal of discovery programs for novel therapeutics targeting GCH1 or SPR.
Gene_expression (targeting) of GCH1 associated with pain, tetrahydrobiopterin and gch1
8) Confidence 0.66 Published 2010 Journal Curr Opin Investig Drugs Section Abstract Doc Link 20047156 Disease Relevance 0.49 Pain Relevance 0.75
Because different mutations in the same gene can result in diverse phenotypes, we sequenced all coding exons of the DYT1, DYT5a, DYT5b, DYT6, DYT11, DYT12, and DYT16 genes in 44 CRPS patients with fixed dystonia to investigate whether high-penetrant causal mutations play a role in CRPS.
Gene_expression (exons) of DYT5a associated with complex regional pain syndromes and dystonia
9) Confidence 0.65 Published 2010 Journal J. Neurol. Section Abstract Doc Link 20066431 Disease Relevance 1.22 Pain Relevance 0.24
The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and ?
Spec (proposed) Gene_expression (proposed) of GCH1 associated with gch1
10) Confidence 0.60 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2759922 Disease Relevance 1.04 Pain Relevance 0.96
The three SNPs in GCH1; rs10483639, rs3783641 and rs8007267, which capture the pain protective haplotype [17] and two SNPs in OPRM1; rs563649 and rs1799971 (A118G), were genotyped in all cases (n = 197) and all controls (n = 197).
Gene_expression (genotyped) of GCH1 associated with pain and gch1
11) Confidence 0.60 Published 2009 Journal Mol Pain Section Body Doc Link PMC2759922 Disease Relevance 0.57 Pain Relevance 0.59
The rate-limiting enzyme in BH4 synthesis, guanosine triphosphate cyclohydrolase 1 (GCH1), and sepiapterin reductase (SPR) are both promising drug targets based on initial active-site characterization of the SARs of these two enzymes.
Gene_expression (synthesis) of GCH1 associated with tetrahydrobiopterin and gch1
12) Confidence 0.59 Published 2010 Journal Curr Opin Investig Drugs Section Abstract Doc Link 20047156 Disease Relevance 0.54 Pain Relevance 0.79
In a study going from initial pathway identification to human pain variation, Tegeder
               et al. [35] recently described the involvement of
               tetrahydrobiopterin (BH4, a cofactor in nitric oxide, serotonin, and catecholamine
               production) and its synthesising enzyme GTP cyclohydrolase (GCH-1)
               in pain sensitivity. 
Gene_expression (synthesising) of GCH-1 associated with pain, tetrahydrobiopterin, catecholamine and serotonin
13) Confidence 0.53 Published 2008 Journal PLoS Genetics Section Body Doc Link PMC2432024 Disease Relevance 0.89 Pain Relevance 1.66
The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and ?
Spec (proposed) Gene_expression (proposed) of cyclohydrolase associated with gch1
14) Confidence 0.52 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2759922 Disease Relevance 1.04 Pain Relevance 0.95
GCH1 encodes GTP cyclohydrolase which is a pathway synthesis enzyme for Tetrahydrobiopterin (BH4), a cofactor essential in neurotransmitter synthesis which is up-regulated in neuropathic and inflammatory pain [9].
Gene_expression (synthesis) of cyclohydrolase associated with neurotransmitter, tetrahydrobiopterin, ipn, neuropathic pain and gch1
15) Confidence 0.52 Published 2009 Journal Mol Pain Section Body Doc Link PMC2759922 Disease Relevance 1.68 Pain Relevance 1.55
Hence, in order to produce functional benefit, a combination of viral vectors expressing both GTP cyclohydrolase 1 (GCH1; a key enzyme in BH4 synthesis) and tyrosine hydroxylase is required.
Gene_expression (expressing) of GCH1 associated with tetrahydrobiopterin and gch1
16) Confidence 0.49 Published 2008 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2626922 Disease Relevance 0.14 Pain Relevance 0.52
In a study going from initial pathway identification to human pain variation, Tegeder
               et al. [35] recently described the involvement of
               tetrahydrobiopterin (BH4, a cofactor in nitric oxide, serotonin, and catecholamine
               production) and its synthesising enzyme GTP cyclohydrolase (GCH-1)
               in pain sensitivity. 
Gene_expression (synthesising) of cyclohydrolase associated with pain, tetrahydrobiopterin, catecholamine and serotonin
17) Confidence 0.46 Published 2008 Journal PLoS Genetics Section Body Doc Link PMC2432024 Disease Relevance 0.88 Pain Relevance 1.66
Hence, in order to produce functional benefit, a combination of viral vectors expressing both GTP cyclohydrolase 1 (GCH1; a key enzyme in BH4 synthesis) and tyrosine hydroxylase is required.
Gene_expression (expressing) of cyclohydrolase 1 associated with tetrahydrobiopterin and gch1
18) Confidence 0.43 Published 2008 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2626922 Disease Relevance 0.14 Pain Relevance 0.52
The circled numbers indicate potential sites of intervention: 1, L-arginine supplementation. 2, Inhibition of protein arginine N-methyltransferase type I (PRMT-I) to prevent the formation of asymmetric dimethyl-L-arginine (ADMA). 3, Increased expression and/or activity of dimethylarginine dimethylaminohydrolase-2 (DDAH-2) to facilitate ADMA catabolism. 4, Inhibition of arginase-2 to prevent L-arginine metabolism. 5, Increased expression and/or activity of endothelial nitric oxide synthase (eNOS). 6, Design of drugs that evoke endothelium-dependent relaxations. 7, Enhanced expression and/or activity of guanosine triphosphate cyclohydrolase (GTPCH), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, or direct supplementation with BH4 or its precursor sepiapterin. 8, Enhanced expression and/or activity of dihydrofolate reductase (DHFR), involved in BH4 regeneration. 9, Scavengers of reactive oxygen species (ROS), antioxidants. 10, Inhibition of the activity and/or expression of enzymes that generate ROS, such as NAD(P)H oxidases (NOX), cyclooxygenases (COX), lipoxygenases (LOX), or cytochrome P450 monooxygenases (P450). 11, Enhanced expression and/or activity of enzymes that metabolize ROS, such as superoxide dismutase (SOD) or catalase (or, alternatively, synthesis of mimetics). 12, Stimulation of soluble guanylyl cyclase (sGC). 13, Activation of sGC. 14, Inhibition of phosphodiesterase-5 (PDE-5). 15, Inhibition of soluble epoxide hydrolase (sEH) to suppress degradation of epoxyeicosatrienoic acids (EETs). 16, Opening calcium-activated potassium channels of small, intermediate, or large conductance (SKCa, IKCa, BKCa). 17, Opening transient receptor potential channels (TRP).
Gene_expression (expression) of guanosine triphosphate cyclohydrolase in endothelium associated with tetrahydrobiopterin, trp channel and potassium channel
19) Confidence 0.10 Published 2010 Journal Curr Hypertens Rep Section Body Doc Link PMC2910890 Disease Relevance 0.18 Pain Relevance 0.28

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