Because myeloid cells constitute a major non-neuronal source of BH4 that may contribute to BH4-dependent phenotypes, we studied here the contribution of myeloid-derived BH4 to pain and itch in lysozyme M Cre-mediated GCH1 knockout (LysM-GCH1<sup>-/-</sup> ) and overexpressing mice (LysM-GCH1-HA).
Three genes involved in DA neurotransmission (COMT, GCH1, and DRD2) have been associated with variability in pain sensitivity, development of CPSP, and analgesic requirement.
The patients with DRD had, when compared with controls, significantly reduced levels of BH4, neopterin, biopterin, and GTPCH1 in their urine, blood, or cytokine-stimulated fibroblasts, but their pain response with respect to non-painful stimulation, (acute) stimulus-evoked pain, or pain response after capsaicin-induced sensitization was not significantly different.
The GCH1pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21-5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture.
The aim of our study was to determine whether single-nucleotide polymorphisms (SNP) in the GCH1 gene affect susceptibility and/or pain sensitivity in fibromyalgia syndrome (FM).
KCNS1, but not GCH1, is associated with pain intensity in a black southern African population with HIV-associated sensory neuropathy: a genetic association study.
However, among patients with current treatment (n = 36), there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC) therapy on coital pain (p = 0.04) as well as on pressure pain thresholds on the arm (p = 0.04).
A GCH1pain-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.
Translational approaches have also been used to verify the importance of experimentally discovered pain pathways in humans, such as GTP cyclohydrolase 1 and the potassium channel K(v)9.1.
Of the 519 Caucasian patients, data from 424 could be analyzed for functional associations of the formerly named "pain-protective" GCH1 haplotype with the key characteristics of pain therapy being (1) actual pain, (2) opioid dosing, and (3) pain therapy duration.
OPRM1 or GCH1 variants conferring modest "protection" from pain by increasing the tone of the endogenous opioid system or decreasing nitric oxide formation).
The aim of this study was to investigate if there is an association between different SNP combinations in the guanosine triphosphate cyclohydrolase (GCH1) gene and a number of pain behavior related outcomes during labor.
The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP.
Other variants modulate the perception of pain (e.g., OPRM1 or GCH1 variants conferring modest pain protection by increasing the tone of the endogenous opioid system or decreasing nitric oxide formation).
Carriers of the particular GCH1 haplotype addressed in this study had higher thresholds to punctate mechanical pain (von Frey hairs) following local skin inflammation (18.1+/-11.3 vs. 9+/-2.8 g; p=0.005) and, to a lesser degree, to heat pain following capsaicin sensitization (35.2+/-0.9 vs. 36.6+/-2.4 degrees C; p=0.026).
Recent advances in the genetics of pain and pain disorders include the discovery of the role of the sodium ion channel SCN9A in neuropathic pain as well as in inability to experience pain, and of GTP cyclohydrolase (GCH1) in setting the sensitivity to pain in normal individuals and modulating liability to chronic pain.