Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans

OBJECTIVES: To assess the effect of variations in GTP cyclohydrolase gene (GCH1) on pain sensitivity in humans. METHODS: Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated. Genotyping was done for 38 single nucleotide polymorphisms (SNPs) whose heterozygosity > 0.2 in GCH1. Influence of the genetic variations including SNPs and haplotypes on pain sensitivity were analyzed. RESULTS: Minor allele frequencies and linkage disequilibrium show significant differences in European Americans, African Americans, Hispanic Americans and Asian Americans. Association analyses in European Americans do not replicate the previously reported important influence of GCH1 variations on pain sensitivity. CONCLUSION: Considering population stratification, previously reported associations between GCH1 genetic variations and pain sensitivity appear weak or negligible in this well characterized model of pain

Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans

BACKGROUND: Candidate gene studies on the basis of biological hypotheses have been a practical approach to identify relevant genetic variation in complex traits. Based on previous reports and the roles in pain pathways, we have examined the effects of variations of loci in the genes of monoamine neurotransmitter systems including metabolizing enzymes, receptors and transporters on acute clinical pain responses in humans. RESULTS: Variations in the catecholamine metabolizing enzyme genes (MAOA and COMT) showed significant associations with the maximum post-operative pain rating while the serotonin transporter gene (SLC6A4) showed association with the onset time of post-operative pain. Analgesic onset time after medication was significantly associated with the norepinephrine transporter gene (SLC6A2). However, the association between COMT genetic variation and pain sensitivity in our study differ from previous studies with small sample sizes, population stratification and pain phenotype derived from combining different types of pain stimuli. Correcting for multiple comparisons did not sustain these genetic associations between monoamine neurotransmitter systems and pain sensitivity even in this large and homogeneous sample. CONCLUSION: These results suggest that the previously reported associations between genetic polymorphisms in the monoamine neurotransmitter systems and the interindividual variability in pain responses cannot be replicated in a clinically relevant pain phenotype

Kinin B1 receptors contributes to acute pain following minor surgery in humans

<p>Abstract</p> <p>Background</p> <p>Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B₁and B₂receptors. It is generally accepted that the B₂receptor is constitutively expressed, whereas the B₁receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels.</p> <p>Results</p> <p>Tissue injury resulted in a significant up-regulation in the gene expression of B₁and B₂receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B₁and B₂receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B₁and B₂receptors were correlated. Following tissue injury, B₁ligands des-Arg⁹-BK and des-Arg¹⁰-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B₁receptor but not B₂receptor.</p> <p>Conclusions</p> <p>These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B₁receptors may contribute to acute inflammatory pain through TRPV1 activation.</p

Melioidosis diagnostic workshop, 2013.

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions