SENSORY TRANSDUCTION IN NORMAL AND INJURED NERVES

正常和受伤神经的感觉传导

• 批准号: 2267067
• 负责人: DARRELL L TANELIAN
• 金额: $ 24.58万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2267067
• 关键词: C fiber; G protein; analgesia; anesthesia; antibody; biological signal transduction; biomedical equipment development; chemical stimulation; chemoreceptors; cornea; cyclic nucleoside monophosphate; electrophysiology; electrostimulus; fluorescence microscopy; heat stimulus; injury; laboratory rabbit; longitudinal animal study; mechanoreceptors; microelectrodes; nerve endings; nervous system regeneration; neural information processing; pain; second messengers; sensory receptors; sensory thresholds; sodium channel; somatic afferent nerve; stimulus /response; stretch receptors; thermoreceptors; voltage /patch clamp

A-delta and C fiber sensory nerves make us aware of the environment (tactile and thermal sensation), are used for homeostatic regulatory mechanisms, mediate neurotrophic processes, and warn us of impending injury (irritation and pain). Alteration in the normal .physiology of these nerves can result in abnormal sensation, chronic pain and inadvertent injury in man. Despite their importance, little is known about the physiology of these sensory nerves, especially the mechanisms they use to transduce energy. In this proposal, rabbit corneal nerves will be studied using anatomic, electrophysiologic and pharmacologic techniques. The cornea is avascular, nonkeratinized, relatively homogeneous and innervated by only A-delta and C-fibers which terminate as unspecialized 'free' nerve terminals. It is an ideal tissue in which to study peripheral sensory mechanisms since in allows simultaneous visualization and electrophysiologic recording from sensory nerve terminals. In vivo and in vitro cornea preparations have been developed in this laboratory and electrophysiologically characterized. Molecular transduction mechanisms of the four corneal receptor types (mechanical, thermal, chemical and bimodal ) will be studied using, specific ion channel toxins; as well as, antibodies and Probes that interfere selectively with components of second messenger cyclic nucleotide and G-protein systems. The effects of tissue injury and nerve regeneration on spontaneous impulse generation, sensory threshold level, receptor specificity and response characteristics will be determined. Quantitative mechanical, thermal and chemical stimulation will be used to investigate the effects of anesthetics and analgesics on peripheral A-delta and C-fibers. Since the cornea has both sensory and sympathetic innervation, it also holds potential as a model of causalgia and reflex sympathetic dystrophy. Results of these studies will contribute to an understanding of the peripheral nervous systems role in the generation of normal and abnormal sensation including pain. This corneal nerve preparation will provide a system for designing and testing new pharmacologic agents to treat sensory nerve dysfunction.

A-Delta和C纤维感觉神经使我们意识到环境 （触觉和热感觉）用于稳态调节 机制，介导神经营养过程，并警告我们即将受伤 （刺激和疼痛）。 正常生理学的改变 神经会导致异常感觉，慢性疼痛和无意 人受伤。 尽管它们的重要性，但对 这些感官神经的生理学，尤其是它们使用的机制 传递能量。 在此提案中，将研究兔子角膜神经 使用解剖，电生理和药理技术。 这 角膜是血管性的，非界化的，相对均匀的和神经支配的 仅由A-Delta和C纤维终止为无专门的“自由”神经 终端。 它是研究周围感觉的理想组织 机制既可以同时可视化和 来自感觉神经末端的电生理记录。 体内和 该实验室已经开发了体外角膜制剂 电生理特征。 分子转导机制 在四种角膜受体类型（机械，热，化学和 将使用特定的离子通道毒素研究双峰）；也， 抗体和探针有选择地干扰第二个成分 信使环核苷酸和G蛋白系统。 组织的影响 自发冲动产生的伤害和神经再生 阈值水平，受体特异性和响应特征将为 决定。 定量机械，热和化学刺激将 用于研究麻醉和镇痛药对 外围A-Delta和C纤维。 由于角膜具有感官和 同情神经，它也具有因果关系模型的潜力 和反射交感神经营养不良。 这些研究的结果将有助于 了解周围神经系统在 正常和异常感觉的产生，包括疼痛。 这个角膜 神经准备将为设计和测试提供新的系统 治疗感觉神经功能障碍的药理剂。

项目成果

Diltiazem spares corneal A delta mechano and C fiber cold receptors and preserves epithelial wound healing.

地尔硫卓可保护角膜 A δ 机械和 C 纤维冷感受器，并保持上皮伤口愈合。

• 发表时间: 1995
• 期刊: Cornea.
• 作者: Mikulec,AA;Lukatch,HS;Monroe,FA;MacIver,MB
• 通讯作者: MacIver,MB

A new in vitro corneal preparation to study epithelial wound healing.

一种新的体外角膜制剂，用于研究上皮伤口愈合。

• 发表时间: 1992
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Tanelian,DL;Bisla,K
• 通讯作者: Bisla,K

A thermal signal generator probe for the study of neural thermal transduction.

用于研究神经热传导的热信号发生器探针。

• DOI: 10.1109/10.301731
• 发表时间: 1994
• 期刊: IEEE transactions on bio-medical engineering
• 作者: Maluf,NI;McNutt,EL;Monroe,S;Tanelian,DL;Kovacs,GT
• 通讯作者: Kovacs,GT

Concentration-dependent effects of lidocaine on corneal epithelial wound healing.

利多卡因对角膜上皮伤口愈合的浓度依赖性影响。

• 发表时间: 1992
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Bisla,K;Tanelian,DL
• 通讯作者: Tanelian,DL

Structural and functional specialization of A delta and C fiber free nerve endings innervating rabbit corneal epithelium.

支配兔角膜上皮的 A δ 和 C 纤维游离神经末梢的结构和功能特化。

• DOI: 10.1523/jneurosci.13-10-04511.1993
• 发表时间: 1993
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: MacIver,MB;Tanelian,DL
• 通讯作者: Tanelian,DL