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.
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