Brainstem Trigeminal Mechanisms of Orofacial Pain

口面部疼痛的脑干三叉神经机制

• 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
• 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

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。第二个目标将侧重于单一个体的神经生理反应 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。