SCOPE: Identification of Genes Critical to the Development of Chronic Orofacial Neuropathic Pain

Chronic pain is a significant health problem. Evidence suggests epigenetic mechanisms are involved in maintaining chronic pain states. Identification of dysregulated pain-centric genes may lead to novel therapeutic approaches that address the cause of the pain, rather than the symptoms. Using our trigeminal inflammatory compression (TIC) injury mouse model of chronic orofacial neuropathic pain (CONP), we identified many TIC-induced genes in the trigeminal ganglia and determined that manipulation of gene expression prior to, and shortly after TIC (day -5 to day 7 post-TIC injury) with the histone deacetylase inhibitor SAHA, prevented the development of CONP. This project’s primary goals are to 1) identify the “window of opportunity” of SAHA treatment, 2) extend these studies to female mice, 3) corroborate TIC-induced whisker pad hypersensitivity to von Frey fibers using the Orofacial Stimulation Test and 4) demonstrate the feasibility of RNA-seq mediated gene expression profiling of the spinal trigeminal nucleus caudalis (spVc). Briefly, male and female mice will be treated with SAHA 1) before and after, 2) before only, after only, the induction of TIC. Whisker pad hypersensitivity will be determined using von Frey fibers and corroborated with the Orofacial Sensitivity Test (Aim 1) and spVc gene expression profiling will be performed (Aim 2). Upon completion of these studies we will be positioned to study temporal and spatial gene expression changes contributing to the transition to and maintenance of chronic pain.