Brainstem Trigeminal Mechanisms of Orofacial Pain

口面部疼痛的脑干三叉神经机制

基本信息

批准号：
10598592
负责人：
JOSHUA Craig BRUMBERG
金额：
$ 7.7万
依托单位：
QUEENS COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598592
关键词：
Adaptive Behaviors Adult Afferent Neurons Age Analgesics Animal Model Animals Anti Inflammatory Analgesics Area Attenuated Behavior Behavioral Brain Stem Cell Nucleus Chronic Development Devices Discrimination Eating Electrophysiology (science)Elements Estrogens Estrous Cycle Exhibits Face Feeding behaviors Female Fiber Frequencies Functional disorder Grooming Home Hour Hyperalgesia Individual Irritants Knock-out Knockout Mice Ligation Maps Measurement Mechanics Mechanoreceptors Mediating Mus Nerve Neurons Nociception Nociceptors Non-Steroidal Anti-Inflammatory Agents Oral Orofacial Pain Pain Pathway interactions Pattern Population Prevalence Procedures Property Quality of life Reporting Resistance Rodent Role Sensory Sex Differences Spinal Spinal Ganglia Stimulus Structure of trigeminal nerve spinal tract nucleus Study models Testing Texture Therapeutic Intervention Tissues Trigeminal Nuclei Trigeminal System Vertebral column Vibrissae Woman barrel cortex central pain chronic pain conventional therapy dorsal horn drinking experience extracellular feeding homeodomain in vivo male mutant neural circuit neuromechanism neurophysiology nociceptive response object recognition orofacial pain processing painful neuropathy pressure receptive field response targeted treatment transcription factor

Adaptive Behaviors Adult Afferent Neurons Age Analgesics Animal Model Animals Anti Inflammatory Analgesics Area Attenuated Behavior Behavioral Brain Stem Cell Nucleus Chronic Development Devices Discrimination Eating Electrophysiology (science)Elements Estrogens Estrous Cycle Exhibits Face Feeding behaviors Female Fiber Frequencies Functional disorder Grooming Home Hour Hyperalgesia Individual Irritants Knock-out Knockout Mice Ligation Maps Measurement Mechanics Mechanoreceptors Mediating Mus Nerve Neurons Nociception Nociceptors Non-Steroidal Anti-Inflammatory Agents Oral Orofacial Pain Pain Pathway interactions Pattern Population Prevalence Procedures Property Quality of life Reporting Resistance Rodent Role Sensory Sex Differences Spinal Spinal Ganglia Stimulus Structure of trigeminal nerve spinal tract nucleus Study models Testing Texture Therapeutic Intervention Tissues Trigeminal Nuclei Trigeminal System Vertebral column Vibrissae Woman barrel cortex central pain chronic pain conventional therapy dorsal horn drinking experience extracellular feeding homeodomain in vivo male mutant neural circuit neuromechanism neurophysiology nociceptive response object recognition orofacial pain processing painful neuropathy pressure receptive field response targeted treatment transcription factor

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项目摘要

Abstract One of the most common causes of chronic pain, is orofacial pain which has a prevalence of 10-15% in the adult population which increases with age and is more common in women with a significant societal impact. Individuals who experience orofacial pain often do so with no obvious underlying tissue damage. This suggests that their pain is likely due to dysfunction in central pain processing circuitry. We have identified a knockout mouse (Prrxl1 KO) that has chronic orofacial pain, which we will utilize to better understand the neural mechanisms underlying the condition as a necessary step towards targeted therapeutic interventions. Prrxl1 KO mice lack the typical patterning associated with whisker inputs in the trigeminal system. Our preliminary results have revelated that Prrxl1 KO mice posses a facial hyperalgesia and a somatic hypoaglgesia while also displaying excessive facial grooming and feeding issues consistent with a chronic trigeminally medicated orofacial pain. In the first aim we will characterize the behavioral issues experience by the Prrxl1 KO mice via probing with von Frey elements, utilization of a Peltier device and direct applied pressure to the face in Prrxl1KO mice, barrelless mice (which lack cortical patterning) and wild-type animals. Additional home-cage videography will allow for facial grimace and grooming measurements. Responses in the absence and the presence of an analgesic will be compared. The second aim will focus on neurophysiological responses from single neurons in the principle sensory nucleus of the trigeminal (PrV) and the spinal trigeminal nucleus (SpV) in response to mechanical and thermal stimuli to begin to elucidate the neural circuitry underlying orofacial pain.

抽象的慢性疼痛最常见的原因之一是口面痛，有一个成人人口的患病率为10-15％，随着年龄的增长而增加，更多在具有重大社会影响的女性中常见。体验的个人口面上的疼痛通常没有明显的潜在组织损伤。这表明这一点它们的疼痛可能是由于中央疼痛加工回路的功能障碍。我们有鉴定出具有慢性口面疼痛的敲除小鼠（PRRXL1 KO），我们将用来更好地理解这种情况的神经机制朝着有针对性的治疗干预措施迈出的必要步骤。 prrxl1 ko小鼠缺乏与三叉神经系统中的晶须输入相关的典型图案。我们的初步结果表明，Prrxl1 KO小鼠具有面部痛觉过敏和躯体性低湿度，同时还表现出过多的面部美容和喂食与慢性三角药的口腔疼痛一致的问题。在第一个目标中将通过探测来表征PRRXL1 KO小鼠的行为问题经验使用von Frey元素，利用毛皮器设备并直接施加压力 prrxl1ko小鼠的脸部，小鼠（缺乏皮质图案）和野生型动物。额外的家居摄影将允许面部鬼脸和修饰测量。在不存在和存在镇痛的情况下的反应将是比较的。第二个目标将重点放在单个的神经生理反应上三叉神经（PRV）和脊柱三叉神经的主要感觉核中的神经元核（SPV）响应机械和热刺激，以开始阐明神经回路的基础疼痛。