My lab is interested in studying the molecular mechanisms and neuronal circuitry that mediate distinct orofacial pain, using the mouse as a model system. In the craniofacial region, pain transmission is mediated by the trigeminal sensory neurons that innervate diverse tissue on the entire face. Interestingly, the perceived pain originated from different areas is different. For example, the pain of a headache is usually very different from dental pain. Furthermore, different craniofacial regions tend to be associated with or develop distinct chronic pains. We hypothesize that the three trigeminal divisions innervating different targets should express distinct molecular programs and engage in distinct neural circuits, thus enabling them to mediate different orofacial pain.
In Specific Aim 1, we will identify the molecular differences among the separate divisions of trigeminal ganglion using genomic approaches. The goal is to generate comprehensive lists of molecular signatures for neurons innervating distinct head/face regions and answer the question: """"""""How heterogeneous are nociceptive trigeminal neurons"""""""".
In Specific Aim 2, we will use some of the molecular markers that we already identified to genetically map the neuronal projections from specific trigeminal populations and study the nociceptive sensory maps in normal mice and in mice with experimentally induced chronic pain. These studies should allow us to address two fundamental questions in pain research: (1) Do different trigeminal neurons form convergent projections at certain locations in the hindbrain? (2) Is abnormal axon sprouting the structural basis for chronic pain? Finally, in Specific Aim 3, we will test the functions of two of the maxillomandibular expressed transcription factors to prove, in principle, that genes specifically present in some but not all trigeminal divisions are important for either their specialized development requirements or their specific functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016550-05
Application #
7575098
Study Section
Special Emphasis Panel (ZDE1-PW (04))
Program Officer
Kusiak, John W
Project Start
2005-04-05
Project End
2011-02-28
Budget Start
2009-03-01
Budget End
2011-02-28
Support Year
5
Fiscal Year
2009
Total Cost
$361,033
Indirect Cost
Name
Duke University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Chen, Yong; Kanju, Patrick; Fang, Quan et al. (2014) TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor. Pain 155:2662-72
Devereaux, Kelly; Dall'Armi, Claudia; Alcazar-Roman, Abel et al. (2013) Regulation of mammalian autophagy by class II and III PI 3-kinases through PI3P synthesis. PLoS One 8:e76405
da Silva, Susana; Hasegawa, Hiroshi; Scott, Alexandra et al. (2011) Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-beta signaling. Proc Natl Acad Sci U S A 108:3395-400
Wang, L; Budolfson, K; Wang, F (2011) Pik3c3 deletion in pyramidal neurons results in loss of synapses, extensive gliosis and progressive neurodegeneration. Neuroscience 172:427-42
Scott, Alexandra; Hasegawa, Hiroshi; Sakurai, Katsuyasu et al. (2011) Transcription factor short stature homeobox 2 is required for proper development of tropomyosin-related kinase B-expressing mechanosensory neurons. J Neurosci 31:6741-9
da Silva, Susana; Wang, Fan (2011) Retrograde neural circuit specification by target-derived neurotrophins and growth factors. Curr Opin Neurobiol 21:61-7
Zhou, Xiang; Wang, Liangli; Hasegawa, Hiroshi et al. (2010) Deletion of PIK3C3/Vps34 in sensory neurons causes rapid neurodegeneration by disrupting the endosomal but not the autophagic pathway. Proc Natl Acad Sci U S A 107:9424-9
Kessler, Jessica D; Hasegawa, Hiroshi; Brun, Sonja N et al. (2009) N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma. Genes Dev 23:157-70
Hasegawa, Hiroshi; Wang, Fan (2008) Visualizing mechanosensory endings of TrkC-expressing neurons in HS3ST-2-hPLAP mice. J Comp Neurol 511:543-56
Hasegawa, Hiroshi; Abbott, Sara; Han, Bao-Xia et al. (2007) Analyzing somatosensory axon projections with the sensory neuron-specific Advillin gene. J Neurosci 27:14404-14

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