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Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament. Pain

Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 center Dr Building 10 Rm 1N103, Bethesda, MD 20892-1197, USA.
Pain (Impact Factor: 5.84). 07/2004; 109(3):488-96. DOI: 10.1016/j.pain.2004.02.027
Source: PubMed

ABSTRACT 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.

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    • "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 [22]. Curiously, these results were not replicated in a following study from the same research group [19] "
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    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
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    • "The met/met genotype of the COMT Val158Met polymorphism has been associated with higher sensitivity in response to pain stimuli (Zubieta et al., 2003; Diatchenko et al., 2006; Jensen et al., 2009), as well as with high risk for the development of FM (Gürsoy et al., 2003; García-Fructuoso et al., 2006; Matsuda et al., 2010; Barbosa et al., 2012). Nevertheless, it seems that Val158Met SNP alone cannot account for pressure and thermal pain sensitivity (Kim et al., 2004) and that other SNPs (rs6269, rs4633, and rs4818) along the COMT gene locus may interact with Val158Met SNP to determine enzyme activity and to modulate pain sensitivity in healthy individuals (Diatchenko et al., 2006). Thus, for instance, a recent study by Diatchenko et al. (2005, 2006) have defined three genetic variations or haplotypes that determine COMT enzymatic activity and account for approximately 11% of the variability in responses to experimental pain. "
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    ABSTRACT: BACKGROUND: Recent evidence suggests that genetic factors might contribute to individual differences in pain sensitivity, risk for developing clinical pain conditions and efficacy of pain treatments. The purpose of the present study was to investigate the relationship of three common haplotypes of COMT gene affecting the metabolism of catecholamines on pain sensitivity in patients with fibromyalgia (FM). METHODS: One hundred and thirteen FM patients and 65 age-matched healthy volunteers participated in the study. We genotyped four single-nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4818 and rs4680 or Val158Met) and identified haplotypes previously designated as low (LPS), average (APS) and high pain sensitivity (HPS). Thermal, pressure and touch thresholds were also examined using a quantitative sensory testing protocol. RESULTS: The frequency of genetic variations associated with low COMT enzyme activity was significantly higher in FM patients than in healthy volunteers. FM patients were more sensitive to experimental pain than healthy volunteers and, in particular, FM individuals with the met/met genotype (Val158Met SNP) or the HPS-APS haplotypes showing higher sensitivity to thermal and pressure pain stimuli than patients carrying the LPS haplotype or val alleles (Val158Met SNP). No differences due to genotype or haplotypes were found on non-painful touch thresholds. CONCLUSIONS: According with previous research, our findings revealed that haplotypes of the COMT gene and genotypes of the Val158Met polymorphism play a key role on pain sensitivity in FM patients.
    European journal of pain (London, England) 01/2013; DOI:10.1002/j.1532-2149.2012.00153.x · 3.22 Impact Factor
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    • "Even though thermotherapy is effective for relieving pain, the existence of large individual differences in pain sensitivity is reported (Nielsen et al., 2008). Furthermore, genetic influence on the variability in human thermal pain sensitivity associates with gender, ethnicity and psychological temperament (Kim et al., 2004). Therefore, the individual difference should be considered in clinical thermal treatment. "
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    ABSTRACT: OBJECTIVE: To test if orofacial somatosensory perception can be modulated by experimental thermal application in healthy human. METHODS: Twelve men and twelve age-matched women participated. In each session thermal application with 10, 42 or 32°C (cooling, warming, control) was applied to the skin over the right masseter using a thermode. Quantitative sensory testing was performed at the skin over the right (testing side) and left (contralateral side) masseter before, during, after the thermal application. RESULTS: During the cooling, mechanical detection threshold (MDT), mechanical pain threshold (MPT) and pressure pain threshold (PPT) were increased, and mechanical pain sensitivity was decreased at testing side compared with baseline (P<0.005). The MPT and PPT at the contralateral side were also increased (P<0.004). During the warming and control, the MDT was increased at the testing side compared with baseline (P=0.002). The somatosensory sensitivity was decreased during cooling compared to warming and control (P<0.05). No gender differences were found. CONCLUSIONS: This study shows an ipsilateral decrease of cutaneous sensation or pain sensitivity during cooling without gender differences. In addition, hypoalgesia on the contralateral side suggests a central mode of action. SIGNIFICANCE: The results support clinical experiences that cooling may alleviates pain both locally and generally.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 10/2012; 124(3). DOI:10.1016/j.clinph.2012.08.025 · 2.98 Impact Factor
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