Cytokine biomarkers and chronic pain: Association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness
- 1 December 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Pain
- Vol. 152 (12), 2802-2812
- https://doi.org/10.1016/j.pain.2011.09.005
Abstract
Summary Women with widespread vs localized chronic pain exhibit distinctive alterations in molecular-genetic profiles of the inflammatory mediators MCP-1, IL-1ra, IL-8, and TGFβ1. For reasons unknown, temporomandibular disorder (TMD) can manifest as localized pain or in conjunction with widespread pain. We evaluated relationships between cytokines and TMD without or with widespread palpation tenderness (TMD−WPT or TMD+WPT, respectively) at protein, transcription factory activity, and gene levels. Additionally, we evaluated the relationship between cytokines and intermediate phenotypes characteristic of TMD and WPT. In a case-control study of 344 females, blood samples were analyzed for levels of 22 cytokines and activity of 48 transcription factors. Intermediate phenotypes were measured by quantitative sensory testing and questionnaires asking about pain, health, and psychological status. Single nucleotide polymorphisms (SNPs) coding cytokines and transcription factors were genotyped. TMD−WPT cases had elevated protein levels of proinflammatory cytokine monocyte chemotactic protein (MCP-1) and antiinflammatory cytokine interleukin (IL)-1ra, whereas TMD+WPT cases had elevated levels of proinflammatory cytokine IL-8. MCP-1, IL-1ra, and IL-8 were differentially associated with experimental pain, self-rated pain, self-rated health, and psychological phenotypes. TMD−WPT and TMD+WPT cases had inhibited transcription activity of the antiinflammatory cytokine transforming growth factor β1 (TGFβ1). Interactions were observed between TGFβ1 and IL-8 SNPs: an additional copy of the TGFβ1 rs2241719 minor T allele was associated with twice the odds of TMD+WPT among individuals homozygous for the IL-8 rs4073 major A allele, and half the odds of TMD+WPT among individuals heterozygous for rs4073. These results demonstrate how pro- and antiinflammatory cytokines contribute to the pathophysiology of TMD and WPT in genetically susceptible people. Furthermore, they identify MCP-1, IL-1ra, IL-8, and TGFβ1 as potential diagnostic markers and therapeutic targets for pain in patients with TMD.Keywords
This publication has 97 references indexed in Scilit:
- Excess Risk of Temporomandibular Disorder Associated With Cigarette Smoking in Young AdultsThe Journal of Pain, 2012
- Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in GambiansBMC Medical Genetics, 2009
- Cytokine and Chemokine Regulation of Sensory Neuron FunctionPublished by Springer Science and Business Media LLC ,2009
- Common Variants of Inflammatory Cytokine Genes Are Associated with Risk of Nephropathy in Type 2 Diabetes among Asian IndiansPLOS ONE, 2009
- Transforming Growth Factor-β1 Impairs Neuropathic Pain through Pleiotropic EffectsMolecular Pain, 2009
- Treatment with DF 2162, a non‐competitive allosteric inhibitor of CXCR1/2, diminishes neutrophil influx and inflammatory hypernociception in miceBritish Journal of Pharmacology, 2008
- Functional characterization of the human TPH2 5′ regulatory region: untranslated region and polymorphisms modulate gene expression in vitroHuman Genetics, 2007
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- Responses to Drs. Kim and Dionne regarding comments on Diatchenko, et al. Catechol- O -methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain 2006;125:216–24Pain, 2007
- Resolution of inflammation: the beginning programs the endNature Immunology, 2005