MECHANISMS OF ORAL TRIGEMINAL CHEMOGENIC IRRITATION

口腔三叉神经化学刺激的机制

• 批准号: 2126981
• 负责人: BRUCE P BRYANT
• 金额: $ 10.37万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2126981
• 关键词: acidity /alkalinity; acids; action potentials; capsaicin; carbon dioxide; carbonate dehydratase; chemoreceptors; electrostimulus; epithelium; histochemistry /cytochemistry; immunocytochemistry; ion transport; ionic strengths; irritation /irritant; laboratory rat; membrane permeability; neural conduction; neural information processing; neuropharmacology; pain; potassium channel; sensory mechanism; sensory thresholds; somesthesis; stimulus /response; thermoreception; tongue; trigeminal nerve

Oral trigeminal stimulation by acids is involved in the consumption of many beverages and food items. It also signals the presence of noxious substances or pathologies (e.g., inflammation) in the mouth. The mechanisms by which the trigeminal nerve transduces and encodes chemical stimuli is not well understood. Using acids as a relevant class of stimuli, this work seeks to elucidate oral chemonociception and place it in the context of what is understood about cutaneous nociception. The first aim is to understand how the lingual epithelium contributes to or modulates the trigeminal response to acids. Data from neural recordings, transepithelial current measurements and physicochemical characteristics of acids will be correlated to determine the role of the lingual epithelium in the access to and direct stimulation of free nerve endings. These experiments will determine if damage-induced processes are involved. The second aim is to determine how acid stimuli are encoded by the trigeminal system. Single neuron recordings will be obtained in response to a number of acids (strong and weak, including C02) and other chemical trigeminal stimuli as well as to other modalities (heat, cold, and mechanical) of trigeminal stimuli. By classifying neurons according to their response profile, hypotheses concerning the coding of acid stimuli by different types of nociceptors will be tested. Specific transduction mechanisms and coding schemes will further be supported or rejected by studying interactions between acidic and other trigeminal stimuli. The third aim examines the role of several specific mechanisms (H+ sensitive K-channels and carbonic anhydrase-dependent acidification of the epithelium by C02) in conferring chemosensitivity on trigeminal endings. The presence of these and other mechanisms, inferred from initial studies and the literature, will be tested by measuring neural responses to acidic stimuli during pharmacological manipulation of the lingual epithelium. In conjunction with the findings from the neurophysiological studies, cellular localization of carbonic anhydrase and several nociceptive neuropeptides will be used to: a) resolve the relative contribution of neuronal and non-neuronal elements of the epithelium to chemosensitivity; and b) resolve whether some or all acidic stimuli are coded by the same population of nociceptive fibers that respond to endogenous compounds involved in nociceptive processes.

酸的口服三叉神经刺激与消耗 许多饮料和食品。 这也表明有毒物质的存在 口腔中的物质或病变（例如炎症）。 这 三叉神经传导和编码化学物质的机制 刺激还没有被很好地理解。 使用酸作为相关类别 刺激，这项工作旨在阐明口腔化学伤害感受并将其置于 在对皮肤伤害感受的理解的背景下。 这 第一个目标是了解舌上皮如何促进或 调节三叉神经对酸的反应。 来自神经记录的数据， 跨上皮电流测量和理化特性 酸的数量将相互关联以确定舌的作用 上皮细胞进入并直接刺激游离神经末梢。 这些实验将确定损伤引起的过程是否是 涉及。 第二个目标是确定酸刺激是如何编码的 三叉神经系统。 单神经元记录将获得 对多种酸（强酸和弱酸，包括 CO2）和其他酸有反应 化学三叉神经刺激以及其他方式（热、冷、 和机械）三叉神经刺激。 通过对神经元进行分类 根据他们的反应概况，有关酸编码的假设 将测试不同类型伤害感受器的刺激。 具体的 转导机制和编码方案将进一步得到支持或 通过研究酸性和其他三叉神经之间的相互作用而被拒绝 刺激。 第三个目标考察几个具体机制的作用 （H+ 敏感 K 通道和碳酸酐酶依赖性酸化 CO2 的上皮细胞）赋予三叉神经化学敏感性 结局。 这些和其他机制的存在，可以推断为 初步研究和文献将通过测量神经元进行测试 药物操作过程中对酸性刺激的反应 舌上皮。 结合调查结果 神经生理学研究，碳酸酐酶的细胞定位 一些伤害性神经肽将用于：a) 解决 神经元和非神经元元素的相对贡献 上皮细胞对化学敏感性； b) 解决是否部分或全部呈酸性 刺激是由相同的伤害性纤维编码的 对参与伤害感受过程的内源性化合物做出反应。