Brainstem trigeminal mechanisms of orofacial pain

口面部疼痛的脑干三叉神经机制

• 批准号: 10432314
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432314
• 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; 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; 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面部疼痛， 成年人群中的患病率为10-15%，随着年龄的增长而增加，并且患病率更高 在女性中很常见，具有重大的社会影响。个人经历 口面疼痛通常没有明显的潜在组织损伤。这表明 他们的疼痛可能是由于中枢疼痛处理电路的功能障碍。我们有 确定了一个敲除小鼠（Prrxl 1 KO），有慢性口面疼痛，我们将 利用，以更好地了解神经机制的条件下，作为一个 这是采取有针对性的治疗措施的必要步骤。Prrxl 1 KO小鼠缺乏 与三叉神经系统中的须状输入相关的典型图案。我们 初步结果显示Prrxl 1基因敲除小鼠具有面部痛觉过敏， 躯体记忆力减退同时表现出过度的面部梳理和进食 与慢性三叉神经药物口面部疼痛一致在第一个目标中， 将通过探测来表征Prrxl 1 KO小鼠经历的行为问题 与冯弗雷元件，利用珀尔帖装置和直接施加的压力， 在Prrxl 1 KO小鼠、无桶小鼠（其缺乏皮质图案化）和野生型小鼠中， 动物额外的家庭笼摄像将允许面部鬼脸和梳理 测量.在不存在和存在镇痛剂的情况下的反应将是 比较了第二个目标将集中在神经生理反应，从单一的 三叉神经感觉主核（PrV）和三叉神经脊束核中的神经元 核（SpV）对机械和热刺激的反应，开始阐明 口面疼痛背后的神经回路