DENTAL AND OROFACIAL PAIN--BRAIN STEM MECHANISMS

我们NIH支持的研究的长期目标是阐明 急性和慢性的中枢机制和神经可塑性过程 牙科和口腔面部疼痛状况及其控制。我们之前已经 显示三叉神经(V)脑干复合体在加工过程中的作用 来自牙髓以及皮肤和深层组织的传入输入， 牙髓引起的V型脑干神经元可塑性 小传入纤维的去传入或丢失。我们最近也有 记录了C纤维刺激剂和炎症性物质的应用 刺激性芥子油(MO)对深部头面部组织也可诱发 反映一个过程的大鼠V伤害性神经元的神经母细胞变化 类似于最近在脊髓中描述的“中枢敏感化” 伤害性通路；它们伴随着 颌肌肌电活动与N-甲基-D-天冬氨酸的关系 天冬氨酸(NMDA)和阿片类神经化学机制。这些中心 变化和机制已被牵连在发展中 痛觉过敏以及疼痛的扩散和转介，这是 对深层组织的损伤和炎症。我们现在已经获得了初步的 数据显示，在大鼠牙髓中应用MO也可以诱导 由阿片类药物机制调节的颌肌肌电活动增加。 这一急性牙髓炎模型和我们在V脑干的专业知识 复合体使我们能够解决C-纤维激动剂是否会诱导牙髓 炎症也会引起类似于中枢神经母细胞的改变。 V脑干神经元的敏感化及其与NMDA和阿片类药物的关系 机械装置。在接下来的3年里，我们将解决假设I： C纤维刺激剂和炎性刺激性芥子油的应用 钼对大鼠磨牙牙髓亚核神经可塑性的影响 尾核和口亚核神经元在感受野改变中的反映 (RF)和响应属性。尾肌的射频和响应特性 和口腔神经细胞将被记录在MO应用前后 测定C纤维激动剂对V脑干神经元的影响 引起急性牙髓炎。假设二；改变后的接受者 尾侧和口侧神经元诱发的场强和反应特性 C纤维刺激剂和炎性刺激剂的应用 芥子油对大鼠磨牙牙髓的作用与兴奋性氨基酸有关。 机械装置。NMDA拮抗剂MK-801将全身给药 以确定神经可塑性变化是否依赖于NMDA 机械装置。假设III：改变的感受野(RF)和反应 贴敷对尾侧和口侧神经元电特性的影响 C-纤维兴奋剂和炎性芥子油对大鼠磨牙牙髓的影响 涉及阿片类药物机制。阿片类拮抗剂纳洛酮 系统地给药以确定神经可塑性变化涉及到的 一种阿片类药物抑制机制。由于急性或慢性牙痛 自然界通常与炎症(如牙髓炎)有关，如 对中枢V区潜在神经可塑性的研究将提供新的见解 炎症性疼痛的脑干神经机制 果肉。

The long-term objective of our NIH-supported research is to elucidate the central mechanisms and neuroplastic processes underlying cute and chronic dental and orofacial pain conditions and their control. We have previously shown the role of the trigeminal (V) brainstem complex in processing afferent inputs from the tooth pulp as well as cutaneous and deep tissues, and V brainstem neuronal neuroplasticity resulting from pulp deafferentation or loss of small afferent fibers. We have also recently documented that application of the C-fiber excitant and inflammatory irritant mustard oil (MO) to deep craniofacial tissues can also induce neuroblastic changes in rat V nociceptive neurons reflecting a process analogous to the "central sensitization" recently described in spinal nociceptive pathways; they are accompanied by increases in electromyographic (EMG) activity of jaw muscles and involve N-methyl-D- aspartate (NMDA) and opioid neurochemical mechanisms. These central changes and mechanisms have been implicated in the development of the hyperalgesia and spread and referral of pain that are characteristic of injury and inflammation to deep tissues. We have now acquired preliminary data revealing that application of MO to the rat tooth pulp can also induce increased jaw muscle EMG activity that is modulated by an opioid mechanism. This acute pulp inflammatory model and our expertise with the V brainstem complex allow us to address whether C-fiber excitants inducing pulp inflammation also induce neuroblastic changes analogous to those of central sensitization of V brainstem neurons and involving NMDA and opioid mechanisms. Over the next 3 years, we will address Hypothesis I: The application of the C-fiber excitant and inflammatory irritant mustard oil (MO) to the rat molar pulp induces neuroplastic changes in subnucleus caudalis and subnucleus oralis neurons reflected in altered receptive field (RF) and response properties. The RF and response properties of caudalis and oralis neurons will be documented before and after MO application to determine the effects on V brainstem neurons of a C-fiber excitant producing acute pulp inflammation. Hypothesis II; The altered receptive field (RF) and response properties of caudalis and oralis neurons induced by the application of the C-fiber excitant and inflammatory irritant mustard oil (MO) to the rat molar pulp involve excitatory amino acid (EAA) mechanisms. The NMDA antagonist, MK-801 will be administered systemically to determine if the neuroplastic changes are dependent upon NMDA mechanisms. Hypothesis III: The altered receptive field (RF) and response properties of caudalis and oralis neurons induced by the application of the C-fiber excitant and inflammatory mustard oil (MO) to the rat molar pulp involve an opioid mechanism. The opiate antagonist naloxone will be administered systemically to determine of the neuroplastic changes involve an opioid suppressive mechanism. Since dental pain of an acute or chronic nature is commonly associated with inflammation (e.g. pulpitis), such studies of potential central V neuroplasticity will provide new insights into brainstem neural mechanisms underlying inflammatory-related pain from the pulp.