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

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部疼痛。成年人中患病率达 10-15%，且随年龄增长而增加，且患病率更高常见于女性，具有重大的社会影响。经历过的个人口面部疼痛通常是在没有明显的底层组织损伤的情况下发生的。这表明他们的疼痛很可能是由于中枢疼痛处理电路的功能障碍造成的。我们有鉴定出一只患有慢性口面部疼痛的基因敲除小鼠（Prrxl1 KO），我们将利用以更好地理解该病症背后的神经机制采取有针对性的治疗干预措施的必要步骤。 Prrxl1 KO 小鼠缺乏与三叉神经系统中晶须输入相关的典型图案。我们的初步结果显示 Prrxl1 KO 小鼠具有面部痛觉过敏躯体痛觉减退，同时还表现出过度的面部梳理和进食与慢性三叉神经药物治疗的口面部疼痛一致的问题。我们在第一个目标中将通过探测来表征 Prrxl1 KO 小鼠经历的行为问题与冯弗雷元件，利用珀耳帖装置和直接施加压力到 Prrxl1KO 小鼠、无桶小鼠（缺乏皮质图案）和野生型小鼠的面部动物。额外的家庭笼子录像将允许面部表情和修饰测量。在缺乏和存在镇痛剂的情况下的反应将是比较的。第二个目标将集中于单个人的神经生理反应三叉神经主感觉核 (PrV) 和三叉神经脊髓神经元细胞核（SpV）对机械和热刺激的反应开始阐明口面部疼痛的神经回路。