Role of Descending Pain Modulation System in Orofacial Pain

项目总结 TMD是一种流行但知之甚少的疾病，可能很难治疗。许多患者患有 慢性TMD的疼痛在损伤消退或没有明显的潜在组织损伤后持续存在。 因此，他们的疼痛很可能是由于中枢疼痛处理回路功能障碍所致。伤害性是 关于有害刺激的信息从外周组织传递到中枢神经 系统。伤害性信号由下行的疼痛调制系统主动调节，它可以 或抑制或增强伤害性传递。延髓头端腹内侧(RVM)是一种主要的 研究最深入的痛觉调制电路的输出。RVM通过两种方式调制伤害性信息传递 细胞的类别，称为“开细胞”和“离细胞”。RVM中的第三类细胞，称为“中性” 细胞在痛觉调制方面没有明显的功能。RVM输出对伤害性感觉的净效应 对脊髓背角的加工过程进行了广泛的研究，并显示在 持续疼痛的状态。然而，在ON和OFF单元格的变化中，输出的降序 在口腔面部炎症期间，RVM的控制性还没有确定。 这项建议的目标是确定口腔炎症如何改变RVM的输出 离线细胞。具体地说，将使用肌源性TMD的大鼠咬肌炎症模型 来实现这一目标。机械无害性和伤害性刺激引起的细胞放电变化 口腔组织将使用活体电生理学进行量化，以检验力的假设 在有咬肌炎症的动物中，引发RVM神经元反应所需的物质将减少 炎症部位以及远处(具体目标1)。此外，光会导致变化 在RVM细胞的子集中。如果光敏感的RVM细胞的比例和反应性在 持续的疼痛状态，那么光线可以促进疼痛通过RVM传递。因此，这个项目将 验证口腔炎症会增加RVM的光反应性的假设(特定目标2)。 这项工作将大大有助于我们对潜在的神经回路变化的理解 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.