DENTAL AND OROFACIAL PAIN--BRAIN STEM MECHANISMS

牙齿和口面部疼痛——脑干机制

• 批准号: 2129002
• 负责人: BARRY J. SESSLE
• 金额: $ 17.41万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-01-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2129002
• 关键词: C fiber; antidromic impulse; brain stem; capsaicin; chemoreceptors; cutaneous sensory nerve; developmental neurobiology; electrophysiology; experimental brain lesion; glutamates; innervation; laboratory rat; lidocaine; mechanoreceptors; neural information processing; neural plasticity; neuroanatomy; neurons; newborn animals; oral facial pain; single cell analysis; somesthetic sensory cortex; thalamus; trigeminal nerve

Our long-term objectives is to elucidate the central mechanisms and neuroblastic underlying acute and chronic pain. While alterations in C- fiber function have been implicated in several chronic pain conditions, the role of C-fiber afferent in the normal development of neuronal properties in central somatosensory pathways, let alone in the development of disordered pain behavior, is still unclear. C-fibers do provide nociceptive afferent excitatory inputs to V brainstem and spinal and spinal neurons, but recent studies have drawn attention to the possible neuroeffector and neurotrophic influences that C fibers may also exert; these neuroblastic influence including shaping neuronal receptive field and response properties in both nociceptive and non-nociceptive pathways. Do C-fibers have a similar role in the normal development of these properties i the V somatosensory system? We will address this question, by testing: Hypothesis I, that the neonatal depletion of C- fiber afferent produces alterations in the receptive field and response properties of nociceptive neurons in subnucleus caudalis of the adult V brainstem complex; Hypothesis II, that the neonatal depletion of C-fiber afferent produces alterations in the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the subnucleus caudalis of the adult V brainstem complex; and Hypothesis III, that the neonatal depletion of C-fiber afferent produces alterations in the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the main sensory nucleus of the adult V brainstem complex. Since C-fiber primary afferent do not project to the V main sensory nucleus changes associated with neonatal capsaicin administration is an alteration to the modulatory influence that caudalis exerts on main sensory neurons; we will therefore also test: Hypothesis IV, that the neonatal depletion of C-fiber afferent produces alteration in the modulatory influences of subnucleus caudalis on the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the main sensory nucleus of the adult V brainstem complex. For each series of experiments, neonatal rats will be injected with capsaicin to deplete their C-fiber afferent and then at 2-3 months of age we will characterize, and compare with control animals, the properties of neurons in V subnucleus caudalis, which acts as the as the primary brainstem relay of nociceptive information, or in the main sensory nucleus which acts as the principal LTM brainstem relay in the vibrissa pathway to cortex. In both groups of animals, main sensory neuronal properties will also be tested during manipulation of the ascending caudalis modulatory influences by local anesthetic or glutamate injections of caudalis. The significance of these studies lies in their integral link to neuroblastic processes operating in the V brainstem complex and the determinants of receptive field and response properties of V somatosensory neurons, and to the view that altered C-fiber function may be involved in the development of several chronic pain conditions.

我们的长期目标是阐明中央机制， 神经母细胞潜在的急性和慢性疼痛。 虽然在C- 纤维功能与几种慢性疼痛病症有关， C纤维传入在神经元正常发育中的作用 在中央躯体感觉通路的特性，更不用说在 疼痛行为紊乱的发展，目前还不清楚。 C纤维确实 向V脑干和脊髓提供伤害性传入兴奋性输入 和脊髓神经元，但最近的研究引起了人们的注意， 可能的神经效应和神经营养影响，C纤维也可能 这些成神经细胞的影响，包括塑造神经元的接受 伤害性和非伤害性的场和反应特性 途径。 C纤维在正常发育中是否有类似的作用？ V体感系统的这些特性？ 我们将解决这个问题 问题，通过测试：假设一，新生儿C- 纤维传入引起感受野和反应的改变 成年人伏隔核尾侧亚核伤害性感受神经元的特性 脑干复合体;假设II，新生儿C-纤维耗竭 传入产生感受野和反应的改变 低阈值机械感受（LTM）神经元的特性 成人V脑干复合体的尾侧亚核;以及假设III， 新生儿C纤维传入纤维的缺失会导致 低阈值的感受野和反应特性 成年人主要感觉核中的机械感受（LTM）神经元 脑干复合体。 由于C纤维初级传入神经不投射到 新生儿辣椒素引起的第V主感觉核变化 给药是对尾侧神经系统调节作用的改变， 施加于主要感觉神经元;因此，我们也将测试：假设 第四，新生儿C纤维传入纤维的消耗产生改变， 在尾侧亚核对感受性的调节作用中， 低阈值机械感受性（LTM）的场和反应特性 成年人V脑干复合体的主要感觉核中的神经元。 对于每个系列的实验，新生大鼠将注射 辣椒素耗尽他们的C纤维传入，然后在2-3个月大的时候， 我们将描述并与对照动物进行比较， V核尾侧亚核的神经元，作为主要的 脑干传递伤害性信息，或在主要的感觉 在触须中作为主要LTM脑干中继的核 通往皮质的通道 在两组动物中，主要感觉神经元 在操控提升的过程中， 局部麻醉剂或谷氨酸盐对尾侧肌的调节作用 注射尾肌。 这些研究的意义在于， 与V型脑干中的成神经细胞过程有着不可分割的联系 复合体和感受野及反应特性的决定因素 的V体感神经元，并认为改变C纤维功能， 可能参与了几种慢性疼痛状况的发展。