Article

Exploring the genetic susceptibility of chronic widespread pain: The tender points in genetic association studies

ARC Epidemiology Unit, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT.
Rheumatology (Oxford, England) (Impact Factor: 4.48). 06/2008; 47(5):572-7. DOI: 10.1093/rheumatology/ken027
Source: PubMed

ABSTRACT

Chronic widespread pain (CWP) is a prevalent disorder associated with a low pain threshold and increased levels of psychological
distress. Evidence indicates that there is a genetic component to CWP syndromes and pain sensitivity. Here we have identified
and reviewed the current literature on genetic association (GA) studies of CWP and pain sensitivity by searching MEDLINE and
EMBASE between January 1990 and May 2007. Of the 18 candidate genes studied to date, no definitive susceptibility genes have
been identified. This review highlights the key issues for consideration when interpreting the findings from existing studies
and in designing future studies to ensure robust and comparable findings in this field. Well-designed GA studies are essential
if the genetic component to CWP aetiology is to be fully determined.

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    • "The relative contribution of the different genes to the variance in clinical and experimental pain responses remains unknown [14]. Preclinical evidence, as well as gene association studies in animals and humans, suggests that the genetic contributions to pain perception vary across pain modalities [15] [16] [17]. 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 [17]. "
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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.
    Full-text · Article · Jan 2015 · BioMed Research International
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    • "It is apparent that some chronically painful pathophysiological processes, such as lumbar disc degeneration (Battie et al., 2007), have a clear genetic contribution but the genetic contribution to chronic pain itself is less clear. Biologically, there is evidence in mice of genetic transmission of nociception (Mogil et al., 1999), and there is growing evidence of specific genetic contributions to some pain conditions in humans (Mogil, 2004; Diatchenko et al., 2006; Limer et al., 2008; Max and Stewart, 2008; Costigan et al., 2010; Hocking et al., 2010; Reimann et al., 2010; Holliday et al., 2010a; Holliday et al., 2010b). These suggest that at least some components of the pain pathway are subject to the effects of measurable genetic variation, irrespective of the cause of the pain. "
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    ABSTRACT: 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 well-characterized, 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.
    Full-text · Article · Aug 2012 · European journal of pain (London, England)
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    • "Familial aggregation should be a clue for some genetic contribution, but does not concretely prove a genetic link, as factors such as environment or a triggering event need to be taken into consideration. Candidate genes implicated in FMS include those controlling serotonin mechanisms, dopamine receptors, as well as metabolism of catecholamines [7] [61]. "
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    ABSTRACT: Fibromyalgia (FMS) is a valid clinical condition that affects 2%-4% of the population with a pivot symptom of widespread body pain. The cause and cure of FMS are as yet unknown. The concept of FMS has evolved over the past two decades to incorporate symptoms beyond pain as contributing to the global spectrum of suffering. FMS is now recognized to be grounded in the neurological domain with evidence of dysregulation of pain processing. Appreciation of the neurophysiologic mechanisms operative in FMS has contributed to rational treatment recommendations, although a "gold standard treatment" does not currently exist. Ideal treatments for FMS patients should be individualized with emphasis on active patient participation, good health practices, and multimodal intervention, incorporating nonpharmacologic and pharmacologic treatments. Predictors of outcome, which is favourable in over 50% of patients, are unknown, but those with better outcome do more physical activity and use fewer medications.
    Full-text · Article · Jan 2012 · Pain Research and Treatment
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