MECHANISM OF NOCICEPTION INDUCED BY INNOCUOUS COLD IN TRIGEMINAL SYSTEM

无害寒冷引起三叉神经系统伤害的机制

• 批准号: 8024732
• 负责人: JIANGUO GU
• 金额: $ 35.53万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-11 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8024732
• 关键词: Accounting; Air; Anatomy; Animal Model; Animals; Behavioral; Body part; Brain Stem; Breathing; Burning Mouth Syndrome; Calcium; Cephalic; Chronic; Clinical; Clinical Treatment; Clothing; Code; Cold Therapy; Dental; Dental Pulp; Disease; Environmental Wind; Esthesia; Face; Fiber; Goals; Head and Neck Cancer; Image; Injury; Ion Channel; Lead; Life; Maintenance; Mediating; Molecular; Neurobiology; Neurologic; Neurons; Nociception; Nociceptors; Oral cavity; Orofacial Pain; Outcome; Pain; Pain Disorder; Painless; Pathway interactions; Patients; Pattern; Peripheral; Records; Reflex Sympathetic Dystrophy; Sensory; Stimulus; Structure of trigeminal ganglion; Symptoms; Synapses; System; Techniques; Temperature; Temperature Sense; Temporomandibular Joint Disorders; Testing; Tooth structure; Trigeminal Nerve Diseases; Trigeminal Neuralgia; Trigeminal System; Trigeminal nerve structure; afferent nerve; base; cancer pain; cold temperature; inflammatory neuropathic pain; nerve injury; new therapeutic target; novel; oral infection; orofacial; patch clamp; receptor; sensory system; somatosensory; surgical pain; transmission process

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 the severe painful sensation induced by cooling temperatures that would normally produce innocuous or pleasant cooling sensation. Unfortunately, the current clinical treatments are unsatisfactory for this chronic orofacial pain condition. This is largely due to the poor understanding of sensory coding mechanisms for cold stimuli in trigeminal sensory system. Several ion channels including TRPM8, TRPA1 and K2P have recently be proposed to be candidates of cold-sensing receptors. The overall goal of this proposal is to identify, in chronic orofacial pain conditions, I) Which of these cold-sensing receptor candidates are involved in innocuous cold- induced orofacial pain, and II) What peripheral and central neuronal mechanisms are responsible for the maintenance of chronic orofacial pain induced by innocuous cold. Advanced neurological techniques including patch-clamp records and calcium imaging together with other approaches including retrograde tracing, immunostaining and 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. PUBLIC HEALTH RELEVANCE Orofacial pain conditions are significant clinical problems that have not been treated satisfactorily due to the poor understanding of neuronal and molecular mechanisms. This project will use advanced neurobiological approaches and animal models to identify thermal receptors and neuronal mechanisms that are involved in an orofacial pain state induced by innocuous (non-painful) cold temperatures, a condition seen in patients with trigeminal neuropathy and other pathological disorders in orofacial regions. The accomplishment of the Aims proposed in this project will lead to novel therapeutic targets for treating some 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却温度通常会产生无害或令人愉悦的冷却感觉引起的严重疼痛感。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三叉刺激系统中冷刺激的感觉编码机制的理解不足。最近已提出包括TRPM8，TRPA1和K2P在内的几个离子通道是冷感应受体的候选者。该提案的总体目的是在慢性口面疼痛条件下识别这些冷感应受体候选者中的哪一种参与无害的冷诱导的口面疼痛，ii）ii）什么是什么是造成慢性口面疼痛的外周和中心神经元机制，导致无害的冷冷。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，包括逆行追踪，免疫染色和动物模型。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。公共卫生相关性的类种族疼痛状况是严重的临床问题，由于对神经元和分子机制的理解不足，因此没有得到令人满意的治疗。该项目将使用先进的神经生物学方法和动物模型来鉴定由无害（非虐待）冷温度引起的口面疼痛状态涉及的热受体和神经元机制，这是一种在口腔神经病和其他病理疾病的患者中看到的疾病。该项目提出的目标的实现将导致用于治疗某些口面疼痛状况的新型治疗靶标。