Arthritis and musculoskeletal disorders, including temporomandibular joint disorders (TMD), are chronic pain conditions that occur more frequently in women of reproductive age than men. Current status of the neural mechanisms of articular pain has relied mainly on experimental models of the knee or ankle joint. However, organizational differences between trigeminal and spinal systems suggest the mechanisms that mediate deep craniofacial pain cannot be fully understood from results obtained by other models of joint pain. The proposed experiments use an animal model to study nociceptive signaling from the temporomandibular joint (TMJ) by neurons in the lower trigeminal brainstem under naive conditions and during chronic inflammation. The overall goal of this study is to test the hypothesis that sex steroid hormones influence central neural processing of sensory signals arising from TMJ region.
Aim 1 determines if sex steroid replacement therapy (estrogen and progesterone) modifies neural activity evoked by stimulating the TMJ.
Aim 2 determines if sex steroids act through glutamate receptors to modify processing of nociceptive signals from the TMJ.
Aim 3 determines if mitogen-activated protein (MAP) kinase, a transduction pathway shared by estrogen and nerve growth factor, contributes to processing of nociceptive signals from the TMJ. Three approaches are used to provide converging lines of evidence: c-fos immunocytochemistry determines neural population responses at single cell resolution, microdialysis determines amino acid transmitter release and electrophysiological recording determines the properties of individual trigeminal neurons that encode sensory input from the TMJ region. This information may lead to a better understanding of how the brain integrates pain-like signals relevant for TMD in women

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
7R01DE012758-09
Application #
7243715
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (05))
Program Officer
Kusiak, John W
Project Start
1998-09-01
Project End
2007-06-30
Budget Start
2006-05-01
Budget End
2006-06-30
Support Year
9
Fiscal Year
2005
Total Cost
$213,706
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Surgery
Type
Schools of Dentistry
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Okamoto, K; Katagiri, A; Rahman, M et al. (2015) Inhibition of temporomandibular joint input to medullary dorsal horn neurons by 5HT3 receptor antagonist in female rats. Neuroscience 299:35-44
Khasabov, Sergey G; Malecha, Patrick; Noack, Joseph et al. (2015) Activation of rostral ventromedial medulla neurons by noxious stimulation of cutaneous and deep craniofacial tissues. J Neurophysiol 113:14-22
Tashiro, A; Bereiter, D A; Thompson, R et al. (2014) GABAergic influence on temporomandibular joint-responsive spinomedullary neurons depends on estrogen status. Neuroscience 259:53-62
Okamoto, Keiichiro; Thompson, Randall; Katagiri, Ayano et al. (2013) Estrogen status and psychophysical stress modify temporomandibular joint input to medullary dorsal horn neurons in a lamina-specific manner in female rats. Pain 154:1057-64
Chang, Z; Okamoto, K; Bereiter, D A (2012) Differential ascending projections of temporomandibular joint-responsive brainstem neurons to periaqueductal gray and posterior thalamus of male and female rats. Neuroscience 203:230-43
Okamoto, Keiichiro; Tashiro, Akimasa; Chang, Zheng et al. (2012) Temporomandibular joint-evoked responses by spinomedullary neurons and masseter muscle are enhanced after repeated psychophysical stress. Eur J Neurosci 36:2025-34
Tashiro, A; Okamoto, K; Bereiter, D A (2012) Rapid estrogenic effects on TMJ-responsive brainstem neurons. J Dent Res 91:210-4
Bereiter, David A; Okamoto, Keiichiro (2011) Neurobiology of estrogen status in deep craniofacial pain. Int Rev Neurobiol 97:251-84
Duenes, Sara L; Thompson, Randy; Chang, Zheng et al. (2010) Psychophysical stress increases the expression of phospho-CREB, Fos protein and neurokinin-1 receptors in superficial laminae of trigeminal subnucleus caudalis in female rats. Neurosci Lett 486:207-10
Tashiro, A; Okamoto, K; Bereiter, D A (2009) Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons. Neuroscience 164:1813-20

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