Facial pain with localized and widespread manifestations: Separate pathways of vulnerability (original) (raw)
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The Journal of Pain, 2011
Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3295 single nucleotide polymorphisms, including ancestryinformative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously-reported associations between TMD and two genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD and they identify potential targets for therapeutic intervention.
Pain medicine (Malden, Mass.), 2016
The objective of this study was to use a genome-wide association (GWAS) approach and pooled DNA strategy to search for new genomic loci associated with complex regional pain syndrome (CRPS). The study cohort consisted of 230 patients with established diagnosis of CRPS. The control group consisted of 230 age- and gender-matched subjects without chronic pain. We tested the association of common single nucleotide polymorphisms (SNPs), genotyped using a high-density microarray platform, with CRPS phenotype. This was followed by individual genotyping of the most significant SNPs identified in the microarray genomic scan, in both original discovery (N = 115) and independent verification (N = 115) groups of patients with CRPS, as well as in the appropriate matched control subjects. The results of our study provide no support for the initial hypothesis of the existence of an association between any investigated genomic targets (including GWAS for all genomic loci available on the microarray...
Human Molecular Genetics, 2004
Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS) and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population, and five combinations of these haplotypes are strongly associated (P 5 0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity when compared with the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD.
Recent advances in the understanding of genetic susceptibility to chronic pain and somatic symptoms
Current rheumatology reports, 2011
Regional (e.g., low back) and widespread chronic pain disorders are common in the general population and are known to be heritable. Recent research suggests that genetic factors increase the risk of developing chronic pain independent of the site of pain. Candidate gene studies have been conducted on key pathways to elucidate susceptibility genes that are likely to be involved in both the sensory and affective components of pain. Findings have been largely equivocal, predominantly due to small sample size, but larger studies of pain in general population samples are being conducted. Interesting candidate genes from animal models and monogenic pain disorders are beginning to emerge. Recent advances in genetics research have yet to make an impact in the pain field but provide considerable scope for future research efforts.
The Role of Genetic Polymorphisms in Chronic Pain Patients
International journal of molecular sciences, 2018
It is estimated that the total annual financial cost for pain management in the U.S. exceeds 100 billion dollars. However, when indirect costs are included, such as functional disability and reduction in working hours, the cost can reach more than 300 billion dollars. In chronic pain patients, the role of pharmacogenetics is determined by genetic effects on various pain types, as well as the genetic effect on drug safety and efficacy. In this review article, we discuss genetic polymorphisms present in different types of chronic pain, such as fibromyalgia, low back pain, migraine, painful peripheral diabetic neuropathy and trigeminal neuralgia. Furthermore, we discuss the role of CYP450 enzymes involved in metabolism of drugs, which have been used for treatment of chronic pain (amitriptyline, duloxetine, opioids, etc.). We also discuss how pharmacogenetics can be applied towards improving drug efficacy, shortening the time required to achieve therapeutic outcomes, reducing risks of s...
Chronic tension-type facial pain- a pilot study on HTTLPR genetic polymorphisms
Rhinology Online, 2019
Background: This study looked at the association between serotonin transporter gene variants and with chronic persistent tension-type facial pain. Known as triallelic 5-HTTLPR, the serotonin transporter gene-linked polymorphic region and its rs25531 polymorphism have been linked to alterations in pain perception. Patients and methods: Genotype polymorphism analysis was carried out in 26 patients with chronic tension type facial pain unresponsive to or recurring after treatment with amitriptyline. Findings were compared to 33 asymptomatic age-and gendermatched controls. Blood serotonin levels in these two groups were also determined. Results: Consistent with previous studies, patients with chronic pain had significantly lower blood serotonin compared to controls. In all genotypes, blood serotonin was low compared to controls and this difference was significant in patients homozygous for the L allele. Conclusion: In this small pilot study, patients with the LL genotype seemed to have the best clinical outcome after three-year follow-up.
Heritability of chronic pain in 2195 extended families
European Journal of Pain, 2012
Chronic pain is pathological, persisting beyond normal tissue healing time. Previous work has suggested~50% variation in chronic pain development is heritable. No data are currently available on the heritability of pain categorized using the Chronic Pain Grade (CPG). Furthermore, few existing studies have accounted for potential confounders that may themselves be under genetic control or indeed 'heritable' non-genetic traits. This study aimed to determine the relative contributions of genetic, measured and shared environmental and lifestyle factors to chronic pain. Chronic pain status was determined and CPG measured in participants from Generation Scotland: the Scottish Family Health Study, a large cohort of wellcharacterized, extended families from throughout Scotland, UK. Heritability estimates (h 2) for 'any chronic pain' and 'severe' chronic pain (CPG 3 or 4) were generated using SOLAR software, with and without adjustment for shared household effects and measured covariates age, body mass index, gender, household income, occupation and physical activity. Data were available for 7644 individuals in 2195 extended families. Without adjustment, h 2 for 'any chronic pain' was 29% [standard errors (SE) 6%; p < 0.001], and for 'severe' chronic pain was 44% (SE 3%; p <0.001). After adjustment, 'any chronic pain' h 2 = 16% (SE 7%; p = 0.02) and 'severe' chronic pain h 2 = 30% (SE 13%; p = 0.007). Co-heritability of both traits was 11% (SE 76%). This study supports the use of chronic pain as a phenotype in genetic studies, with adequate correction for confounders to specifically identify genetic risk factors for chronic pain.
Genome-wide Association Study of Multisite Chronic Pain in UK Biobank
Chronic pain is highly prevalent worldwide, contributing a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype, chronic pain grade, have been shown to be complex, heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual’s overall sensitivity to experiencing and reporting chronic pain have also been suggested. We have here made use of a measure of the number of sites of chronic pain in individuals within the general UK population. This measure, termed Multisite Chronic Pain (MCP), is also a complex trait, but its genetic architecture has not previously been investigated. To address this, a large-scale genome-wide association study (GWAS) of MCP was carried out in ~380,000 UK Biobank participants to identify associated genetic variants. Findings were consistent with MCP having a significant polygenic component with a SNP heritability of 10.2...