Painful temporomandibular joint disorders (TMJO) involve deep tissues including muscle and joint. The etiology and pathology of these disorders remain unclear. This project has been dedicated to developing animal models of deep pain in the craniomandibular region and pursuing studies of the function of the trigeminal brainstem sensory nuclei arid surrounding structures in persistent inflammatory pain conditions. We have demonstrated that masseter inflammation activated distinct regions in the spinal trigeminal nucleus (Vsp), the subnucleus interpolaris/caudalis transition zone (Vi/Vc) and the more caudal laminated subnucleus caudalis contiguous with the upper cervical dorsal horn (Vc/Ci,2). Further, the Vi/Vc transition zone plays an important role in the processing of orofacial inputs related to deep tissue injury. In light of our previous findings and recent developments on neuronal plasticity and persistent pain, we propose to extend our studies by further identifying the cellular and molecular mechanisms of the trigeminal processing of deep orofacial input after inflammation in the next grant period with an emphasis on neuronal-glial interactions. Our major hypotheses are that 1) orofacial deep tissue injury induces neuronal plasticity in the ViA/c transition zone of the Vsp through activation of glia and 2) ViA/c glial activation and inflammatory cytokine release affect or facilitate neuronal plasticity through interactions with neuronal glutamate receptors and play a critical role in the development of inflammatory hyperalgesia. These hypotheses will be tested in rat models of tissue injury and plasticity by a combination of approaches involving immunohistochemistry, immunoprecipitation, Western blot, behavior testing and the neuropharmacological method.
Aim 1 will test the hypothesis that glial cells are activated in the ViA/c of Vsp after masseter inflammation and affect neuronal function through release of inflammatory cytokines.
Aim 2 will determine whether primary afferent input plays a role in glial activation after orofacial inflammation.
Aim 3 will test the hypothesis that ViA/c glial activation and associated cytokine release facilitate neuron plasticity through interaction with neuronal glutamate receptors and play a critical role in the development of inflammatory hyperalgesia. These studies will elucidate the significance of glial-cytokine-neuronal interactions in the development of orofacial hyperalgesia and further establish the importance of the trigeminal transition zone in response to orofacial deep injury. The findings will advance our understanding of the mechanisms of persistent pain associated with TMJD and facilitate the designing of new therapeutic approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE011964-14
Application #
8090323
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Kusiak, John W
Project Start
1996-09-15
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2014-06-30
Support Year
14
Fiscal Year
2011
Total Cost
$345,467
Indirect Cost
Name
University of Maryland Baltimore
Department
Dentistry
Type
Schools of Dentistry
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Guo, Wei; Imai, Satoshi; Yang, Jia-Le et al. (2017) In vivo immune interactions of multipotent stromal cells underlie their long-lasting pain-relieving effect. Sci Rep 7:10107
Guo, Wei; Imai, Satoshi; Dubner, Ronald et al. (2014) Multipotent stromal cells for arthritic joint pain therapy and beyond. Pain Manag 4:153-62
Ren, Ke (2012) Further evidence on a role of chemokines in injury-related pain hypersensitivity: commentary on a paper by Saika et al. (2012, this issue). Eur J Pain 16:1209-10
Guo, Wei; Wang, Hu; Zou, Shiping et al. (2012) Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation. Neurosci Bull 28:193-207
Chai, Bryan; Guo, Wei; Wei, Feng et al. (2012) Trigeminal-rostral ventromedial medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury. Mol Pain 8:78
Guo, Wei; Wang, Hu; Zou, Shiping et al. (2011) Bone marrow stromal cells produce long-term pain relief in rat models of persistent pain. Stem Cells 29:1294-303
Ren, Ke; Dubner, Ronald (2011) The role of trigeminal interpolaris-caudalis transition zone in persistent orofacial pain. Int Rev Neurobiol 97:207-25
Yang, Kun; Takeuchi, Keita; Wei, Feng et al. (2011) Activation of group I mGlu receptors contributes to facilitation of NMDA receptor membrane current in spinal dorsal horn neurons after hind paw inflammation in rats. Eur J Pharmacol 670:509-18
Guo, Wei; Wang, Hu; Zou, Shiping et al. (2010) Long lasting pain hypersensitivity following ligation of the tendon of the masseter muscle in rats: a model of myogenic orofacial pain. Mol Pain 6:40
Ren, Ke (2010) Emerging role of astroglia in pain hypersensitivity. Jpn Dent Sci Rev 46:86

Showing the most recent 10 out of 53 publications