Target Genes of Inflammatory Temporomandibular Pain

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DESCRIPTION (provided by applicant): Chronic pain is a common clinical syndrome lacking specific and effective therapeutic agents due to the fact that cellular mechanisms of chronic pain are poorly understood. Clinical observations and pharmacological data from experimental animal models have indicated that chronic pain states, including that of orofacial pain, derived from different etiologies have distinct biochemical and pharmacological characteristics, suggesting specific mechanisms for different pain states. A large body of experimental data indicates that altered expression of selected genes in sensory neurons and associated segments of spinal cord may play a special role in neuroplasticity contributing to a specific pain state. We hypothesize that changes in expression of specific genes and their related pathways in trigeminal ganglia, subnucleus caudalis and upper cervical spinal cord may be responsible for the development of chronic orofacial pain states after deep temporomandibular joint inflammation. To test this hypothesis, we plan to use Affymetrix gene chips to examine the gene expression profiles in trigeminal ganglia (containing sensory neurons) and the associated subnucleus caudalis/spinal cord segments of male rats with or without deep temporomandibular joint inflammation. We will identify those genes with specific regulation post inflammation that are also associated with the temporal development of chronic pain. Potential pathways underlined by interactions of identified genes or between identified genes and other genes will be studied using computer assisted data mining. Expression of selective genes from the gene chip analysis will be validated with alternative techniques including real-time PCR, in situ hybridization and Western blots. The potential contribution of selective genes to chronic pain development will be determined by pharmacological, and molecular biology approaches in future studies. The outcome of this study should provide a global view of genomic responses in the trigeminal-spinal complex to orofacial deep-tissue inflammation. Identification of specifically regulated genes and pathways under this condition will provide a focused target gene pool for further investigations of molecular mechanisms underlying chronic pain states post temporomandibular joint infection.