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

Limer, K.L.; Nicholl, Barbara I; Thomson, Wendy; McBeth, John

doi:10.1093/rheumatology/ken027

Cited by 39 publications

(30 citation statements)

References 54 publications

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“…Genes that code for proteins in the opioid system (such as OPRM1) are implicated in both the processing of somatic pain and the formation of social attachments (95, 100). Polymorphisms in the μ-opioid receptor gene, d-opioid receptor subtype 1 gene, and catechol-O-methyltransferase gene were all associated with increased sensitivity to experimentally induced pain (101, 102). Mice lacking μ-opioid receptor genes exhibited less attachment-related behaviors, such as separation vocalizations and reactions to maternal cues (95).…”

Section: Multidisciplinary Research Findingsmentioning

confidence: 99%

Somatoform Pain

Landa

Peterson

Fallon

2012

Psychosomatic Medicine

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Somatoform pain is a highly prevalent, debilitating condition and a tremendous public health problem. Effective treatments for somatoform pain are urgently needed. The etiology of this condition is, however, still unknown. On the basis of a review of recent basic and clinical research, we propose one potential mechanisms of symptom formation in somatoform pain and a developmental theory of its pathogenesis. The emerging evidence from animal and human studies in developmental neurobiology, cognitive-affective neuroscience, psychoneuroimmunology, genetics, epigenetics, and clinical and treatment studies of somatoform pain all point to the existence of a shared physical and social pain neural system. Research findings also show that non-optimal early experiences interact with genetic predispositions to influence the development of this shared system and ability to regulate it in an effective way. Interpersonal affect regulation between infant and caregiver is crucial for the optimal development of these brain circuits. The aberrant development of this shared neural system during infancy, childhood and adolescence, therefore, may ultimately lead to an increased sensitivity to physical and social pain and to problems with their regulation in adulthood. The authors critically review translational research findings that support this theory and discuss its clinical and research implications. Specifically, the proposed theory and reviewed research suggest that psychotherapeutic and/or pharmacologic interventions that foster the development of affect regulation capacities in an interpersonal context will also serve to more effectively modulate aberrantly activated neural pain circuits and thus be of particular benefit in the treatment of somatoform pain.

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Section: Multidisciplinary Research Findingsmentioning

confidence: 99%

Somatoform Pain

Landa

Peterson

Fallon

2012

Psychosomatic Medicine

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“…A number of studies have examined genetic variants for CWP. These candidate gene studies examined polymorphisms in genes involved in both the peripheral and the central nervous system 8. In particular, genes involved in neurotransmission (pathway of dopamine and serotonin9–19), and genes important for the hypothalamic–pituitary–adrenal axis have been considered 20.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region

et al. 2012

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Objectives Chronic widespread pain (CWP) is a common disorder affecting ~10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP. Methods We conducted a GWAS meta-analysis in 1,308 female CWP cases and 5,791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1,480 CWP cases and 7,989 controls (P<1×10−5). Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain. Results The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of CCT5 and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (MAF=43%; OR=1.30, 95%CI=1.19-1.42, P=1.2×10−8). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95%CI=1.10-1.24, P=4.7×10−7) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95%CI=1.14-1.32, P=3.4×10−8, I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (P>7.7×10−4). Conclusions We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.

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“…This is in contrast to another study that found that the S (low expressing) allele was associated with being less sensitive to heat, cold, and pressure pain compared with the L (high expressing allele) [45,46] in healthy individuals. FM patients are reported to be more sensitive to sensory stimuli, however, and the S allele was associated with an increased risk of FM in earlier studies [19]. However, comorbid psychological traits such as depression, in which serotonin is important, may also influence pain sensitivity, making it difficult to determine the polymorphism's true effect.…”

Section: The Serotonergic Systemmentioning

confidence: 96%

“…As previously reviewed, the evidence for the involvement of 5HTTLPR in chronic widespread pain is equivocal [19]. Potvin et al [44] reported no difference in genotype frequency between FM patients (n=58) and healthy controls (n=60).…”

Section: The Serotonergic Systemmentioning

confidence: 99%

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Recent Advances in the Understanding of Genetic Susceptibility to Chronic Pain and Somatic Symptoms

Holliday

McBeth

2011

Curr Rheumatol Rep

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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.

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

Cited by 39 publications

References 54 publications

Somatoform Pain

Somatoform Pain

Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region

Recent Advances in the Understanding of Genetic Susceptibility to Chronic Pain and Somatic Symptoms

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