Role of Descending Pain Modulation System in Orofacial Pain

项目摘要 TMD是一种普遍存在但知之甚少的疾病，很难治疗。 慢性TMD在损伤消退或没有明显的潜在组织损伤后仍有疼痛。 因此，他们的疼痛很可能是由于中枢疼痛处理电路功能障碍。伤害感受是 将有害刺激的信息从外周组织传递到中枢神经 系统伤害性信号由下行疼痛调节系统主动调节， 抑制或增强伤害性传递。延髓头端腹内侧（RVM）是一个主要的 这是研究得最好的痛觉调制电路的输出。RVM通过两个途径调节伤害性传递 细胞类别，称为“ON-细胞”和“OFF-细胞”。RVM中的第三类单元，称为“中性 细胞”在疼痛调节中没有明显的功能。RVM输出对伤害性感觉的净效应 脊髓背角的加工已经被广泛研究，并显示在脊髓背角的加工中会发生改变。 持续疼痛的状态。然而，ON和OFF单元格中的变化， RVM的控制，在口面部炎症尚未确定。 本提案的目标是确定口面炎症如何改变RVM ON和 关闭细胞。具体而言，将使用大鼠中肌源性TMD的咬肌炎症模型 来实现这一目标。机械性刺激引起的神经元放电的变化 将使用体内电生理学对口面组织进行量化，以检验力 在咬肌炎症动物中，引起RVM神经元反应所需的量将减少， 炎症部位以及远处位置（特定目标1）。此外，光导致变化 在RVM小区的子集中。如果RVM中光敏细胞的比例和反应性增加， 持续性疼痛状态，则光可促进疼痛通过RVM传递。因此，该项目将 检验口面部炎症会增加RVM的光反应性的假设（具体目标2）。 这项工作将大大有助于我们了解神经回路的变化， 慢性TMD

PROJECT SUMMARY TMD is a prevalent, but poorly understood condition that can be difficult to treat. Many patients with chronic TMD have pain that continues after injury resolution or no obvious underlying tissue damage. Their pain is thus most likely due to dysfunction in central pain processing circuitry. Nociception is the transmission of information about harmful stimuli from the peripheral tissues to the central nervous system. Nociceptive signals are actively regulated by descending pain-modulatory systems, which can either dampen of enhance nociceptive transmission. The rostral ventromedial medulla (RVM) is a major output of the best-studied pain-modulation circuit. RVM modulates nociceptive transmission via two classes of cells, termed “ON-cells” and “OFF-cells.” A third class of cells in RVM, referred to as “NEUTRAL cells,” have no apparent function in pain-modulation. The net effect of RVM output on nociceptive processing in the dorsal horn of the spinal cord has been studied extensively, and shown to be altered in states of persistent pain. However, the changes in ON- and OFF cells, the output of the descending control from RVM, during orofacial inflammation have not been determined. The goal of this proposal is to determine how orofacial inflammation changes the outputs of RVM ON- and OFF-cells. Specifically a masseter muscle inflammation model of myogenous TMD in the rat will be used to achieve this goal. Changes in cell firing evoked by innocuous and noxious mechanical stimulation of orofacial tissues will be quantified using in vivo electrophysiology to test the hypothesis that the force required to elicit an RVM neuronal response will be decreased in animals with masseter inflammation, at the site of inflammation as well as at distant locations (Specific Aim 1). Additionally, light leads to changes in a subset of RVM cells. If the proportion and responsiveness of light sensitive RVM cells increases in states of persistent pain, then light could facilitate pain transmission through RVM. Thus, this project will test the hypothesis that orofacial inflammation will increase light responsiveness of RVM (Specific Aim 2). This work will contribute significantly to our understanding of the neural circuitry changes underlying chronic TMD.