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

Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society
D C BulmerQ Aziz

Abstract

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. 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. 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 w...Continue Reading

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Jun 8, 2012·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·A SharmaQ Aziz

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Citations

Jan 31, 2016·Current Treatment Options in Gastroenterology·Jan TackAns Pauwels
Apr 28, 2021·Molecular Genetics and Metabolism·Nastassja HimmelreichBeat Thöny

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