Disorders of the temporomandibular joint (TMJ) and muscles of mastication often result in persistent pain and therefore are a major health problem. Women appear to be affected more than men. The underlying etiology and pathology associated with these disorders remains unclear.
The aims of this study are to develop an animal model in which behavioral, physiological, pharmacological and molecular events associated with deep tissue injury and inflammation of the orofacial region can be compared with events following inflammation of cutaneous tissues. The major hypothesis is that orofacial deep tissue injury leads to a cascade of molecular, biochemical and physiological events resulting in prolonged functional changes in the brain associated with persistent pain and hyperalgesia.
Specific Aim 1 is to develop an animal model to characterize nocifensive responses to the injury of deep or cutaneous orofacial tissues in the rat. Inflammatory agents will be injected into the TMJ capsule or surrounding tissues, or into the perioral (PO) skin. Quantitative behavioral measures of hyperalgesia associated with TMJ/PO inflammation will be established. The working hypothesis is that hyperalgesia of deep tissues will refer to cutaneous zones but that the reverse will be rare or not encountered.
Specific Aim 2 is to demonstrate the sensitivity of the model to antihyperalgesic.and analgesic agents. These experiments will test the hypothesis that this model involves excitatory amino acid (EAA) receptor activation and that the subtypes of EAA receptors are differentially involved in hyperalgesia following deep and cutaneous tissue injury.
Specific Aim 3 is to investigate the excitability of trigeminal brain stem nociceptive neurons after TMJ or PO persistent inflammation.
Specific Aim 4 will determine the anatomical distribution of neurons in the medullary dorsal horn that exhibit changes in excitability after inflammation of the TMJ or PO tissues. The changes in Fos protein immunohistochemistry will be examined.
Specific Aim 5 will determine the effects of TMJ vs PO inflammation on neuropeptide gene expression in the medullary dorsal horn. We hypothesize that deep and cutaneous tissue inflammation will produce differential effects. These findings will provide insight into the mechanisms of central hyperexcitability and behavioral hyperalgesia after orofacial tissue inflammation. It will be important to our understanding of the development of persistent pain associated with temporomandibular disorders.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Special Emphasis Panel (ZDE1-GH (11))
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University of Maryland Baltimore
Schools of Dentistry
United States
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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
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
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
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

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