While a variety of cultural, psychological and physiological factors contribute to variability in both clinical and experimental contexts, the role of genetic factors in human pain sensitivity is increasingly recognized as an important element. This study was performed to evaluate genetic influences on variability in human pain sensitivity associated with gender, ethnicity and temperament. Pain sensitivity in response to experimental painful thermal and cold stimuli was measured with visual analogue scale ratings and temperament dimensions of personality were evaluated. Loci in the vanilloid receptor subtype 1 gene (TRPV1), delta opioid receptor subtype 1 gene (OPRD1) and catechol O-methyltransferase gene (COMT) were genotyped using 5' nuclease assays. A total of 500 normal participants (306 females and 194 males) were evaluated. The sample composition was 62.0% European American, 17.4% African American, 9.0% Asian American, and 8.6% Hispanic, and 3.0% individuals with mixed racial parentage. Female European Americans with the TRPV1 Val(585) Val allele and males with low harm avoidance showed longer cold withdrawal times based on the classification and regression tree (CART) analysis. CART identified gender, an OPRD1 polymorphism and temperament dimensions of personality as the primary determinants of heat pain sensitivity at 49 degrees C. Our observations demonstrate that gender, ethnicity and temperament contribute to individual variation in thermal and cold pain sensitivity by interactions with TRPV1 and OPRD1 single nucleotide polymorphisms.
"The rs8065080 polymorphism is predicted to reside within membrane-spanning helix 5 and affects the transmembrane domain, which confers responsiveness to capsaicin (chili peppers). This SNP consists of an G>A substitution, resulting in an isoleucine to valine change at codon 585; female European Americans homozygous for the isoleucine-allele showed longer pain response time to cold and heat stimuli . Curiously, these results were not replicated in a following study from the same research group  "
[Show abstract][Hide abstract] ABSTRACT: It is suggested that genetic variations explain a significant portion of the variability in pain perception; therefore, increased understanding of pain-related genetic influences may identify new targets for therapies and treatments. The relative contribution of the different genes to the variance in clinical and experimental pain responses remains unknown. It is suggested that the genetic contributions to pain perception vary across pain modalities. For example, it has been suggested that more than 60% of the variance in cold pressor responses can be explained by genetic factors; in comparison, only 26% of the variance in heat pain responses is explained by these variations. Thus, the selection of pain model might markedly influence the magnitude of the association between the pain phenotype and genetic variability. Thermal pain sensation is complex with multiple molecular and cellular mechanisms operating alone and in combination within the peripheral and central nervous system. It is thus highly probable that the thermal pain experience is affected by genetic variants in one or more of the pathways involved in the thermal pain signaling. This review aims to present and discuss some of the genetic variations that have previously been associated with different experimental thermal pain models.
BioMed Research International 01/2015; 2015:349584. DOI:10.1155/2015/349584 · 2.71 Impact Factor
"To check for gender differences in the genotypic effects, “gender” was introduced in a further combined analysis, however, at an exploratory level as the study was not powered for gender differences. Moreover, while the original study reporting a function of the TRPA1 rs11988795 G>A variant also reported interactions in the modulation of pain between gender and several variants in other genes , gender interaction was not reported for TRPA1 variants and therefore not a major factor to be introduced in the present study design. Further statistical analyses included cross-tabulations, rank correlations (Spearman’s ρ) and effect size calculations using Cohen’s d (values of 0.2, 0.5 and 0.8 being indicative of a small, medium and large effect size, respectively ). "
[Show abstract][Hide abstract] ABSTRACT: TRPA1 ion channels are involved in nociception and are also excited by pungent odorous substances. Based on reported associations of TRPA1 genetics with increased sensitivity to thermal pain stimuli, we therefore hypothesized that this association also exists for increased olfactory sensitivity.
Olfactory function and nociception was compared between carriers (n = 38) and non-carriers (n = 43) of TRPA1 variant rs11988795 G>A, a variant known to enhance cold pain perception. Olfactory function was quantified by assessing the odor threshold, odor discrimination and odor identification, and by applying 200-ms pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and heat stimuli, and 200-ms intranasal pulses of CO2).
Among the 11 subjects with moderate hyposmia, carriers of the minor A allele (n = 2) were underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049). Moreover, carriers of the A allele discriminated odors significantly better than non-carriers (13.1±1.5 versus 12.3±1.6 correct discriminations) and indicated a higher intensity of the H2S stimuli (29.2±13.2 versus 21±12.8 mm VAS, p = 0.006), which, however, could not be excluded to have involved a trigeminal component during stimulation. Finally, the increased sensitivity to thermal pain could be reproduced.
The findings are in line with a previous association of a human TRPA1 variant with nociceptive parameters and extend the association to the perception of odorants. However, this addresses mainly those stimulants that involve a trigeminal component whereas a pure olfactory effect may remain disputable. Nevertheless, findings suggest that future TRPA1 modulating drugs may modify the perception of odorants.
PLoS ONE 04/2014; 9(4):e95592. DOI:10.1371/journal.pone.0095592 · 3.23 Impact Factor
"TRPV1 is expressed on articular chondrocytes18, as well as intraarticular nerve fibre terminals19,20. Ile-585-val TRPV1 variants are reported to confer reduced sensitivity to cold pain21,22. The Ile–Ile variant is associated with lower risk of symptomatic vs asymptomatic knee OA (odds ratio (OR) = 0.74) in a cohort of 3270 symptomatic vs 1098 asymptomatic cases23. "
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) accounts for the majority of the disease burden for musculoskeletal disorders and is one of the leading causes of disability worldwide. This disability is the result not of the cartilage loss that defines OA radiographically, but of the chronic pain whose presence defines symptomatic OA. It is becoming clear that many genes, each with a small effect size, contribute to the risk of developing OA. However, the genetics of OA pain are only just starting to be explored. This review will describe the first genes to have been identified in genomic studies of OA pain, as well as the possible dual roles of genes previously identified in genomic studies of OA in the context of pain. Difficulties associated with attempting to characterise the genetics of OA pain will be discussed and promising future avenues of research into genetic and epigenetic factors affecting OA pain described.
Osteoarthritis and Cartilage 09/2013; 21(9):1374-82. DOI:10.1016/j.joca.2013.06.010 · 4.17 Impact Factor
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