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.

酸口服三叉神经刺激参与 许多饮料和食品。 它还表示有害的存在 口腔中的物质或病理（例如炎症）。 这 三叉神经转导和编码化学的机制 刺激不太了解。 使用酸作为相关类 刺激，这项工作旨在阐明口服chemonocticeating并放置 在有关皮肤伤害感受的情况下。 这 第一个目的是了解舌上皮如何贡献或 调节对酸的三叉神经反应。 来自神经记录的数据， 旋转电流测量和物理化学特征 酸的相关以确定舌的作用 上皮在进入和直接刺激自由神经末端。 这些实验将确定损害引起的过程是否为 涉及。 第二个目的是确定酸刺激的编码 三叉神经系统。 单个神经元记录将在 对许多酸（包括C02）和其他酸的反应 化学三叉神经刺激以及其他方式（热，冷， 和三叉神经刺激的机械）。 通过对神经元进行分类 对于他们的响应概况，关于酸编码的假设 将测试不同类型的伤害感受器的刺激。 具体的 转导机制和编码方案将进一步支持或 通过研究酸性和其他三叉新闻之间的相互作用而拒绝 刺激。 第三目检查了几种特定机制的作用 （H+敏感的K通道和碳赤铁酶依赖性酸化 C02的上皮赋予三叉神经的化学敏感性 结局。 这些机制的存在，从 初始研究和文献将通过测量神经来测试 在药理学操纵过程中对酸性刺激的反应 舌上皮。 结合了来自 神经生理学研究，碳酸酐酶的细胞定位 并且将使用几种伤害性神经肽来：a）解决 神经元和非神经元元素的相对贡献 上皮化学敏感性； b）解决某些或所有酸性 刺激是由相同的伤害性纤维人群编码的 对参与伤害性过程的内源性化合物的反应。