Molecular Profiling Core. Fibromyalgia (FM), irritable bowel syndrome (IBS), vulvar vestibulitis syndrome (WS), and episodic migraine (EM) are prevalent complex persistent pain conditions (CPPCs). CPPCs commonly aggregate as comorbid conditions and are characterized by a report of pain greater than expected upon physical examination. Because we do not understand the efiology of CPPCs, patients receive inadequate treatment and suffer severe physiologic, psychologic, and socioeconomic consequences. Recent studies suggest that CPPCs are mediated in large part by genefic variability which can produce functional consequences on the amount and/or activity of proteins, which regulate downstream signaling events that impact pain-relevant processes. However, little is known about the specific nature of the relationship between genotype and biologic activity and their relevance to clinical phenotype. Thus, the objective of the Molecular Profiling Core is to identify biologic mediators that contribute to CPPCs. This goal will be achieved through execution of three specific aims.
In Aim I, FM, IBS, WS, and EM cases and pain free controls (N = 300 per group) will be genotyped using the Pain Research Panel developed by our investigative team to measure neariy 3,000 polymorphisms in 350 genes whose protein products are linked to biologic pathways that influence pain transmission, inflammatory response, or psychological state.
In Aim II, changes in the expression of proteins corresponding to the 350 genes represented on the Pain Research Panel will be measured in plasma and leukocytes from cases and controls using custom protein microarray technology. Results of these studies will allow us to evaluate changes in protein expression patterns that direcfiy result from functional polymorphisms. Moreover, they will inform the design of studies associated with Aim III, which is to create a lymphoblast repository that will provide an in vivo system within which to model cell signaling processes based on genefic and protein analyses. Elucidating the pathophysiologic mechanisms that underlie CPPCs will facilitate the long-term goal of our program which is to provide more accurate subdiagnoses as well as individualized therapeutic regimens to individuals who suffer from these conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS045685-10
Application #
8650341
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
10
Fiscal Year
2014
Total Cost
$323,906
Indirect Cost
$98,878
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Smith, Shad B; Reenilä, Ilkka; Männistö, Pekka T et al. (2014) Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain. Pain 155:2390-9
Lambert, Cynthia A; Sanders, Anne; Wilder, Rebecca S et al. (2014) Chronic HPA axis response to stress in temporomandibular disorder. J Dent Hyg 88 Suppl 1:5-12
Hartung, Jane E; Ciszek, Brittney P; Nackley, Andrea G (2014) ?2- and ?3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain 155:1346-55
van Tilburg, Miranda A L; Zaki, Essam A; Venkatesan, Thangam et al. (2014) Irritable bowel syndrome may be associated with maternal inheritance and mitochondrial DNA control region sequence variants. Dig Dis Sci 59:1392-7
Sanders, Anne E; Slade, Gary D; Bair, Eric et al. (2013) General health status and incidence of first-onset temporomandibular disorder: the OPPERA prospective cohort study. J Pain 14:T51-62
Diatchenko, Luda; Fillingim, Roger B; Smith, Shad B et al. (2013) The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol 9:340-50
Chen, Hong; Nackley, Andrea; Miller, Vanessa et al. (2013) Multisystem dysregulation in painful temporomandibular disorders. J Pain 14:983-96
Slade, Gary D; Bair, Eric; Greenspan, Joel D et al. (2013) Signs and symptoms of first-onset TMD and sociodemographic predictors of its development: the OPPERA prospective cohort study. J Pain 14:T20-32.e1-3
Wagner, I Janelle; Damitz, Lynn A; Carey, Erin et al. (2013) Bilateral accessory breast tissue of the vulva: a case report introducing a novel labiaplasty technique. Ann Plast Surg 70:549-52
Sanders, A E; Essick, G K; Fillingim, R et al. (2013) Sleep apnea symptoms and risk of temporomandibular disorder: OPPERA cohort. J Dent Res 92:70S-7S

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