RGD Reference Report - Evidence of a role for GTP cyclohydrolase-1 in visceral pain. - Rat Genome Database

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Evidence of a role for GTP cyclohydrolase-1 in visceral pain.

Authors: Bulmer, D C  Botha, C A  Wheeldon, A  Grey, K  Mein, C A  Lee, K  Knowles, C H  Winchester, W J  Aziz, Q 
Citation: Bulmer DC, etal., Neurogastroenterol Motil. 2015 May;27(5):656-62. doi: 10.1111/nmo.12538. Epub 2015 Mar 17.
RGD ID: 401700391
Pubmed: PMID:25783971   (View Abstract at PubMed)
DOI: DOI:10.1111/nmo.12538   (Journal Full-text)


BACKGROUND: The enzyme guanosine triphosphate-cyclohydrolase-1 (GCH-1) is a rate limiting step in the de novo synthesis of tetrahydrobiopterin (BH4) a co-factor in monoamine synthesis and nitric oxide production. GCH-1 is strongly implicated in chronic pain based on data generated using the selective GCH-1 inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP), and studies which have identified a pain protective GCH-1 haplotype associated with lower BH4 production and reduced pain.
METHODS: To investigate the role for GCH-1 in visceral pain we examined the effects of DAHP on pain behaviors elicited by colorectal injection of mustard oil in rats, and the pain protective GCH-1 haplotype in healthy volunteers characterized by esophageal pain sensitivity before and after acid injury, and assessed using depression and anxiety questionnaires.
KEY RESULTS: In rodents pretreatment with DAHP produced a substantial dose related inhibition of pain behaviors from 10 to 180 mg/kg i.p. (p < 0.01 to 0.001). In healthy volunteers, no association was seen between the pain protective GCH-1 haplotype and the development of hypersensitivity following injury. However, a substantial increase in baseline pain thresholds was seen between first and second visits (26.6 ± 6.2 mA) in subjects who sensitized to esophageal injury and possessed the pain protective GCH-1 haplotype compared with all other groups (p < 0.05). Furthermore the same subjects who sensitized to acid and possessed the haplotype, also had significantly lower depression scores (p < 0.05).
CONCLUSIONS & INFERENCES: The data generated indicate that GCH-1 plays a role in visceral pain processing that requires more detailed investigation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GCH1HumanVisceral Pain treatmentISOGch1 (Rattus norvegicus) RGD 
GCH1HumanVisceral Pain treatmentIAGP DNA:haplotypeRGD 
Gch1RatVisceral Pain treatmentISOGCH1 (Homo sapiens)DNA:haplotypeRGD 
Gch1RatVisceral Pain treatmentIMP  RGD 
Gch1MouseVisceral Pain treatmentISOGCH1 (Homo sapiens)DNA:haplotypeRGD 
Gch1MouseVisceral Pain treatmentISOGch1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gch1  (GTP cyclohydrolase 1)

Genes (Mus musculus)
Gch1  (GTP cyclohydrolase 1)

Genes (Homo sapiens)
GCH1  (GTP cyclohydrolase 1)


Additional Information