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 #
3P01NS045685-08S1
Application #
8457071
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
8
Fiscal Year
2012
Total Cost
$49,428
Indirect Cost
$11,859
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Ciszek, Brittney P; O'Buckley, Sandra C; Nackley, Andrea G (2016) Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors. Anesthesiology 124:1122-35
Moss, Chailee F; Damitz, Lynn A; Gracely, Richard H et al. (2016) Dorsal clitoral nerve injury following transobturator midurethral sling. J Pain Res 9:727-730
Oladosu, Folabomi A; Ciszek, Brittney P; O'Buckley, Sandra C et al. (2016) Novel intrathecal and subcutaneous catheter delivery systems in the mouse. J Neurosci Methods 264:119-28
Wu, Cindy; Damitz, Lynn; Karrat, Kimberly M et al. (2016) Clitoral Epidermal Inclusion Cyst Resection With Intraoperative Sensory Nerve Mapping Technique. Female Pelvic Med Reconstr Surg 22:e24-6
Ciszek, Brittney P; Khan, Asma A; Dang, Hong et al. (2015) MicroRNA expression profiles differentiate chronic pain condition subtypes. Transl Res 166:706-720.e11
Oladosu, Folabomi A; Conrad, Matthew S; O'Buckley, Sandra C et al. (2015) Mu Opioid Splice Variant MOR-1K Contributes to the Development of Opioid-Induced Hyperalgesia. PLoS One 10:e0135711
Convertino, Marino; Samoshkin, Alexander; Gauthier, Josee et al. (2015) μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids. Prog Neuropsychopharmacol Biol Psychiatry 62:61-7
Applebaum, Elizabeth; Nackley, Andrea G; Bair, Eric et al. (2015) Genetic Variants in Cyclooxygenase-2 Contribute to Post-treatment Pain among Endodontic Patients. J Endod 41:1214-8
Oladosu, Folabomi A; Maixner, William; Nackley, Andrea G (2015) Alternative Splicing of G Protein-Coupled Receptors: Relevance to Pain Management. Mayo Clin Proc 90:1135-51
Meloto, Carolina B; Segall, Samantha K; Smith, Shad et al. (2015) COMT gene locus: new functional variants. Pain 156:2072-83

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