DENTAL AND OROFACIAL PAIN BRAIN STEM MECHANISMS

牙齿和口面部疼痛的脑干机制

• 批准号: 3219148
• 负责人: BARRY J. SESSLE
• 金额: $ 12.7万
• 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 1994-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3219148
• 关键词: antidromic impulse; brain stem; cats; cutaneous sensory nerve; dendrites; dental pulp; electrophysiology; mandible /maxilla; mechanoreceptors; nerve endings; neural information processing; neural inhibition; neural plasticity; neurons; oral facial pain; pain; single cell analysis; temporomandibular joint; trigeminal nerve; trigeminal neuralgia; visceral afferent nerve

The long-term objectives of our research program are to clarify the central mechanisms underlying acute and chronic dental and orofacial pain and its control. Our recent NIH-supported research has resulted in major new insights into the neuroplasticity of the trigeminal (V) brainstem complex, and into brainstem mechanisms underlying deep (e.g. muscle; and temporomandibular joint, TMJ) as well as cutaneous (facial) pain. THE EXPRESSION OF NEUROPLASTICITY THAT WE DOCUMENTED IN THE ADULT v BRAINSTEM COMPLEX WAS REVEALED BY ENDODONTIC DEAFFERENTATION OF THE TOOTH PULP. IN THE SPINAL SOMATOSENSORY SYSTEM, PERIPHERAL DEAFFERENTATION CAN ALSO INDUCE ALTERATIONS IN SOMATOSENSORY PATHWAYS THAT HAVE BEEN VIEWED AS A REFLECTION OF CNS NEUROPLASTICITY AND AS PROCESSES CONTRIBUTING TO THE DEVELOPMENT OF CHRONIC PAIN. THE MECHANISMS AS PROCESSES CONTRIBUTING TO THE DEVELOPMENT OF CHRONIC PAIN. THE MECHANISMS UNDERLYING THESE CHANGES IN INHIBITION OF EXISTING AFFERENT INPUTS. OUR STUDIES OF V BRAINSTEM CELLS INDICATED THAT MAXILLARY OR MANDIBULAR PULP DEAFFERENTATION IN ADULT ANIMALS RESULTED IN STATISTICALLY SIGNIFICANT ALTERATIONS IN MECHANORECEPTIVE FIELD AND RESPONSE PROPERTIES THAT WERE ESPECIALLY APPARENT IN ORALS NEURONS; THESE EFFECTS WERE SIGNIFICANTLY PROLONGED WITH MORE EXTENSIVE PULP DEAFFERENTATION. AS FOR THE SPINAL SYSTEM, HOWEVER, the mechanisms underlying our documented physiological changes after deafferentation of the pulp are unclear. THEREFORE, we will test hypotheses that mandibular pulp deafferentation is associated with (A) SPROUTING OF MAXILLARY AFFERENTS INTO REGIONS OF V SUBNUCLEUS ORALIS NORMALLY DEVOTED TO THE REPRESENTATION OF THE MANDIBULAR DIVISION; (B) a decrease in afferent inhibition; and (C) a decrease in primary afferent depolarization (PAD) WHICH IS CONSIDERED A REFLECTION OF PRESYNAPTIC INHIBITION. Comparison of these features between normal and deafferented adult animals will be made in V brainstem neurons or primary afferents IN QUANTITATIVE ANALYSES UTILIZING, FOR HYPOTHESES B & C, OUR WELL-DOCUMENTED EXPERTISE IN EXTRACELLULAR SINGLE UNIT RECORDING. TO ADDRESS HYPOTHESIS A, NEW APPROACHES FOR OUR LAB INVOLVING HRP LABELLING OF V NERVE BRANCHES AND INTRACELLULAR HRP LABELLING OF PHYSIOLOGICALLY IDENTIFIED SINGLE UNITS WILL BE USED. THESE STUDIES WILL CLARIFY SOME OF THE MECHANISMS THAT MAY BE INVOLVED IN NEUROPLASTIC RESPONSES OF THE V BRAINSTEM COMPLEX TO INJURY OF THE TOOTH PULP AND THAT MAY UNDERLIE THE DEVELOPMENT OF CHRONIC OROFACIAL PAIN.

我们研究计划的长期目标是澄清中心 急、慢性牙科和口腔面疼痛的发病机制及其临床意义 控制力。我们最近由美国国立卫生研究院支持的研究导致了重大的新的 对三叉神经(V)脑干复合体神经可塑性的见解， 以及深部潜在的脑干机制(例如肌肉；以及 TMJ)以及皮肤(面部)疼痛。这个 我们记录的神经可塑性在成年v脑干中的表达 从牙髓的牙髓去传入可见复合体。在……里面 脊髓躯体感觉系统、外周传入的去化也可导致 被视为反射的躯体感觉通路的改变 中枢神经可塑性和AS过程在脑损伤发展中的作用 慢性疼痛。作为促进发展的过程的机制 慢性疼痛的症状。这些变化背后的机制是抑制 现有传入输入。我们对V脑干细胞的研究表明 成年动物上颌髓或下颌髓去传入的实验研究 机械应变场和应变场的统计显著变化 在口腔神经元中特别明显的反应特性；这些 更广泛的牙髓显著延长了疗效。 去感觉神经。然而，至于脊椎系统，其机制 我们记录的去传入后的生理变化 果肉还不清楚。因此，我们将检验下颌骨的假说 牙髓去传入与(A)上颌骨萌发有关 传入口侧V亚核的区域通常专用于 下颌部代表；(B)传入神经减少 抑制；和(C)初级传入去极化(PAD)减少 这被认为是突触前抑制的反映。比较 正常成年动物和去传入成年动物之间的这些特征将被制作出来 脑干V区神经元或初级传入神经元的定量分析 对于假设B和C，利用我们记录良好的专业知识 细胞外单单位记录。为了解决假设A，新的 本实验室涉及V神经分支的HRP标记方法和 生理鉴定的单个单位的细胞内HRP标记将 被利用。这些研究将阐明一些可能的机制 参与V脑干复合体对损伤的神经可塑性反应 牙髓，这可能是慢性口腔颌面部疾病发展的基础 很痛苦。