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）：口面部疼痛疾病涵盖多种病症，包括三叉神经痛、面部反射性交感神经营养不良（RSD）、颞下颌关节紊乱、牙周疼痛、灼口综合征、牙科手术疼痛、头颈癌疼痛、口腔感染引起的疼痛以及其他神经性和炎性疼痛病症。许多慢性口面部疼痛的一种常见症状是由冷却温度引起的严重疼痛感，通常会产生无害或令人愉快的清凉感。不幸的是，目前的临床治疗对于这种慢性口面部疼痛状况并不令人满意。这很大程度上是由于对三叉神经感觉系统冷刺激的感觉编码机制了解不足。最近，包括 TRPM8、TRPA1 和 K2P 在内的几种离子通道被提议作为冷感受体的候选者。该提案的总体目标是确定在慢性口面部疼痛情况下，I）哪些候选冷敏受体与无害的寒冷引起的口面部疼痛有关，以及 II）哪些外周和中枢神经元机制负责维持由无害的寒冷引起的慢性口面部疼痛。该项目将使用先进的神经学技术，包括膜片钳记录和钙成像，以及逆行追踪、免疫染色和动物模型等其他方法。通过实现我们的目标，我们将确定治疗一些顽固性口面部疼痛的新治疗靶点。公众健康相关性 口面部疼痛是重要的临床问题，由于对神经元和分子机制了解甚少，尚未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识别与无害（无痛）低温引起的口面部疼痛状态有关的热受体和神经元机制，这种情况见于三叉神经病和口面部区域其他病理性疾病的患者。该项目提出的目标的实现将为治疗某些口面部疼痛病症带来新的治疗靶点。