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.

摘要 慢性疼痛最常见的原因之一是口腔面部疼痛，它具有 成年人口中10-15%的患病率随着年龄的增长而增加，而且 在具有重大社会影响的女性中很常见。经历过的个人 口腔面部疼痛通常在没有明显的潜在组织损伤的情况下发生。这表明 他们的疼痛可能是由于中枢疼痛处理电路功能障碍所致。我们有 发现了一只患有慢性口面部疼痛的基因敲除小鼠(Prrxl1 KO)，我们将 用来更好地理解这种情况背后的神经机制 朝着有针对性的治疗干预迈出必要的一步。Prrxl1 KO小鼠缺乏 三叉神经系统中与胡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和 躯体吞咽减少，同时也表现出过度的面部修饰和进食 与慢性三叉神经药物治疗口腔面部疼痛相一致的问题。在第一个目标中，我们 将通过探测来描述Prrxl1 KO小鼠经历的行为问题 利用von Frey元件，利用Peltier装置并将压力直接施加到 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做鬼脸和梳妆 测量。在没有止痛剂和存在止痛剂的情况下，反应将是 比较一下。第二个目标将集中在单个人的神经生理反应上 三叉神经感觉主核(PRV)和三叉神经脊束核的神经元 核团(SPV)对机械刺激和热刺激的反应开始阐明 口面部疼痛背后的神经回路。