DENTAL AND OROFACIAL PAIN--BRAIN STEM MECHANISMS

我们NIH支持的研究的长期目标是阐明 中枢机制和神经可塑性过程的基础急性和慢性 牙齿和口面疼痛状况及其控制。 我们先前已经 显示了三叉神经（V）脑干复合体在处理中的作用 来自牙髓以及皮肤和深部组织的传入输入， 和V脑干神经元的神经可塑性导致的纸浆 小传入纤维的传入阻滞或丢失。 我们最近还 记录了C纤维兴奋剂和炎症剂的应用 芥子油（MO）对深部颅面组织的刺激性也可诱导 大鼠V伤害感受神经元的神经母细胞变化反映了一个过程 类似于最近在脊髓中描述的“中枢致敏”， 伤害性通路;它们伴随着 肌电图（EMG）活动的颌肌肉，并涉及N-甲基-D- 天冬氨酸（NMDA）和阿片类神经化学机制。 这些中央 变化和机制已经牵连在发展中的 痛觉过敏以及疼痛扩散和转移是 损伤和炎症。 我们已经初步掌握了 数据显示，MO对大鼠牙髓的应用也可以诱导 增加由阿片机制调节的颌肌EMG活动。 这个急性牙髓炎模型和我们对V型脑干的专业知识 复合物使我们能够解决是否C-纤维兴奋剂诱导纸浆 炎症也诱导类似于中枢神经系统的神经母细胞变化。 V脑干神经元的致敏作用及其与NMDA和阿片的关系 机制等 在接下来的三年里，我们将讨论假设一： C-纤维兴奋性和炎症刺激性芥子油的应用 (MO)致大鼠磨牙髓核亚核神经可塑性改变 尾侧核和口侧亚核神经元在感受野改变中的反映 (RF)和响应特性。 尾侧肌的射频和反应特性 和口肌神经元将在MO应用之前和之后记录， 确定C纤维兴奋剂对V脑干神经元的影响 引起急性牙髓炎。 假设二：接受性改变 场（RF）和反应特性的尾侧和口侧神经元诱导 通过应用C-纤维兴奋剂和炎症刺激剂 芥子油（MO）对大鼠磨牙牙髓的影响与兴奋性氨基酸（EAA）有关 机制等 将全身给予NMDA拮抗剂MK-801 以确定神经可塑性变化是否依赖于NMDA 机制等 假设三：改变的感受野（RF）和反应 尾侧和口侧神经元的性质诱导的应用， C-纤维刺激剂和炎症芥子油（MO）对大鼠磨牙牙髓的影响 涉及阿片类机制。 阿片拮抗剂纳洛酮将被 全身给药以确定神经可塑性变化， 阿片抑制机制 由于牙痛的急性或慢性 性质通常与炎症（例如牙髓炎）有关， 对潜在的中央V神经可塑性的研究将提供新的见解 炎症相关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.