Complex persistent pain conditions (CPPCs) such as headache conditions, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and vulvar vestibulitis are high prevalent and shared or comorbid chronic pain conditions. There are two features of CPPCs that are fundamental to the aims and goals of this proposal: 1) the etiology of CPPCs is multifactorial and 2) the clinical manifestations of CPPCs are diverse. In this Program Project, we expect to identify a mosaic of risk factors for each of five CPPCs: fibromyalgia (FM), episodic migraine (EM), vulvar vestibulitis (VVS), irritable bowel syndrome (IBS), and temporomandibular joint disorders (TMD). Furthermore, we expect to characterize clusters of patients within each CPPC that vary significantly according to manifestations of their condition in addition to its painful characteristics (e.g., fatigue, dysfunction, sleep loss). Importantly, we expect some clusters of patients to be more alike across CPPCs than within any single CPPC, consistent with our view that there is some overlap in the manifestations of CPPCs. A unifying hypothesis integrating this Program is that multiple genetic factors, when coupled with environmental exposures (e.g. injury, infections, physical and psychological stress), increase the susceptibility to highly prevalent CPPCs by enhancing pain sensitivity and/or increasing psychological distress. To address the aims and goals of the subprojects and cores described in this application, a group of accomplished pain clinicians, pain researchers, psychophysiologists, molecular and cellular geneticists, biostatisticians and epidemiologists have been brought together to form this Program. Studies proposed in this Program Project application seek to identify the psychological and physiological risk factors, clusters, and associated genetic polymorphisms, that influence pain amplification and psychological profiles in enrollees who have established CPPDs. Additionally, the proposed studies seek to characterize the biological pathways through which these genetic variations causally influence CPPCs.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Chen, Daofen
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University of North Carolina Chapel Hill
Schools of Dentistry
Chapel Hill
United States
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Zhang, Xin; Hartung, Jane E; Bortsov, Andrey V et al. (2018) Sustained stimulation of ?2- and ?3-adrenergic receptors leads to persistent functional pain and neuroinflammation. Brain Behav Immun 73:520-532
Sigurdsson, Martin I; Waldron, Nathan H; Bortsov, Andrey V et al. (2018) Genomics of Cardiovascular Measures of Autonomic Tone. J Cardiovasc Pharmacol 71:180-191
Kim, Seungtae; Zhang, Xin; O'Buckley, Sandra C et al. (2018) Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions. J Pain 19:1384.e1-1384.e14
Smith, Shad B; Parisien, Marc; Bair, Eric et al. (2018) Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males. Pain :
Suarez-Roca, Heberto; Klinger, Rebecca Y; Podgoreanu, Mihai V et al. (2018) Contribution of Baroreceptor Function to Pain Perception and Perioperative Outcomes. Anesthesiology :
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
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
Maixner, William; Fillingim, Roger B; Williams, David A et al. (2016) Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification. J Pain 17:T93-T107
Ciszek, Brittney P; O'Buckley, Sandra C; Nackley, Andrea G (2016) Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral ?-Adrenergic Receptors. Anesthesiology 124:1122-35
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 264:119-128

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