Mechanism of Nociception Induced by Innocuous Cold in Trigeminal System

无害寒冷引起三叉神经痛觉的机制

• 批准号: 8984706
• 负责人: JIANGUO GU
• 金额: $ 31.58万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-10 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8984706
• 关键词: Mechanism; Nociception; Induced; Innocuous; Cold

DESCRIPTION (provided by applicant): Orofacial pain disorders encompass a wide range of conditions including trigeminal neuralgia, reflex sympathetic dystrophy (RSD) of the face, temporomandibular joint disorders, periodontal pain, burning mouth syndrome, dental surgical pain, head and neck cancer pain, pain due to oral infections, and other neuropathic and inflammatory pain conditions. One common symptom in many chronic orofacial pain conditions is cold allodynia/hyperalgesia, the excruciating painful sensation induced by cooling temperatures that would normally produce innocuous or mild painful cooling sensation. Unfortunately, the current clinical treatments are unsatisfactory for this chronic orofacial pain condition. This is largely due to the poor understanding of mechanisms for controlling cold sensitivity in trigeminal sensory system. We have recently accumulated evidence suggesting that cold sensitivity of nociceptive cold- sensing neurons may largely depend on low-threshold voltage-gated K+ channels (KLT), a subclass of voltage-gated K+ channels that are activated near resting membrane potentials. Furthermore, we found that pharmacologically potentiating KLT channels reversed orofacial cold allodynia/hyperalgesia. In this renewal application, the overall objectives are to study the role of KLT channels in controlling cold sensitivity of nociceptive cold-sensing trigeminal neurons under both physiological and trigeminal neuropathic conditions, and to explore therapeutic use of KLT channel potentiators for treating orofacial cold allodynia and hyperalgesia. Advanced neurological techniques including patch-clamp records and calcium imaging together with other approaches including immunostaining and novel animal models will be used in this project. By accomplishing our goal, we will have identified novel therapeutic targets for treating some intractable orofacial pain conditions.

描述（由申请人提供）：口面疼痛疾病包括各种疾病，包括三叉神经痛，脸部反射交感神经营养不良（RSD），颞下颌关节疾病，牙周关节疼痛，牙口疼痛，牙口综合征，牙科综合征，牙科手术疼痛，头颈疼痛，颈部癌，疼痛，疼痛，疼痛以及其他病毒疗法以及其他Neuropation和其他Neuropation和其他Neuropation和其他肿瘤。在许多慢性口腔疼痛状况中，一种常见的症状是冷垂体/痛觉过敏，这是冷却温度通常会产生无害或轻度疼痛的冷却感觉引起的痛苦感。不幸的是，目前的临床治疗对这种慢性口面疼痛状况不满意。这在很大程度上是由于对控制三叉神经感觉系统中冷灵敏度的机制的理解不足。我们最近积累了证据，表明伤害感冒感应神经元的冷敏感性可能在很大程度上取决于低阈值电压门控的K+通道（KLT），这是电压门控的K+通道的子类，在静止膜电位附近激活。此外，我们发现药理学增强的KLT通道逆转了口面冷异性肌/痛觉过敏。在这种续签应用中，总体目标是研究KLT通道在生理和三叉神经性疾病中控制伤害感受感应三叉神经元冷敏感性的作用，并探索KLT通道增强剂治疗口腔冷质和超级高过度差异的治疗方法。该项目将使用先进的神经系统技术，包括斑块钳记录和钙成像以及其他方法，包括免疫染色和新型动物模型。通过实现我们的目标，我们将确定用于治疗某些棘手的口面疼痛状况的新型治疗靶标。