Neural Circuits Mediating Aversion to Noxious Stimuli

神经回路调节对有害刺激的厌恶

• 批准号: 6565205
• 负责人: HOWARD L FIELDS
• 金额: $ 18.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6565205
• 关键词: analgesia; avoidance behavior; behavior test; behavioral /social science research tag; brain mapping; central neural pathway /tract; cues; dorsal horn; experimental brain lesion; laboratory rat; neural information processing; neural transmission; neuropeptide receptor; neurotoxins; nociceptors; pain; somesthetic sensory cortex; spinal cord mapping; stimulus /response; substance P; thalamic nuclei

DESCRIPTION (from abstract): In contrast to other sensory modalities such as vision and hearing, pain is, by definition, unpleasant at threshold. This unpleasantness is the subjective correlate of a drive to escape and avoid tissue damaging stimuli. Although the clinical importance of the affective-motivational aspect of pain is generally accepted, the lack of a valid animal model has hampered investigation of its neurobiological basis. The research proposed in this project is specifically designed to examine the neural mechanisms of aversion produced by noxious stimuli. The investigators will adapt the place preference apparatus to measure the magnitude of aversion to a context associated with hindpaw formalin injection (condition place aversion or CPA). Rats will receive formalin in a compartment with obvious olfactory, visual and tactile cues. On alternate days they will receive saline in a second compartment. After formalin conditioning, the reduction of time spent in the formalin-associated compartment will be taken as a measure of aversiveness. The effects on formalin elicited CPA of inactivating various CNS structures implicated in nociception will be studied. In the first experiments, rats will receive a substance P receptor neurotoxin, the substance P-saporin-conjugate, in the lumbar intrathecal space to selectively destroy lamina I spinomesencephalic and spinothalamic neurons. If this reduces CPA, rats will be tested for the effects of lesions or transient inactivation of the parabrachial nucleus and of spinothalamic target nuclei and cortical areas activated by noxious stimuli. Thalamic areas to be studied include the ventrobasal complex, the posterior thalamic/posterior intralaminar group and the media thalamic/intralaminar region. The cortical areas to be studied include the somatosensory, anterior cingulate and dysgranular insular cortices. In complementary studies, cortical areas implicated in aversion by inactivation studies will be stimulated using excitatory chemical agents to determine if local neuronal activity can elicit CPA in the absence of a peripheral noxious stimulus. Finally, they will study the effect on formalin behaviors and CPA of reversible inactivation of descending modulatory systems.

描述（来自摘要）：与其他感官方式相比，例如 视觉和听觉，根据定义，疼痛在阈值处是令人不愉快的。这 不愉快是逃避和避免的主观关联 组织损伤性刺激。尽管其临床重要性 疼痛的情感动机方面已被普遍接受，但缺乏 有效的动物模型阻碍了对其神经生物学基础的研究。这 该项目提出的研究专门旨在检查 有害刺激产生厌恶的神经机制。调查人员 将采用位置偏好装置来测量厌恶的程度 与后爪福尔马林注射相关的背景（条件位置 厌恶或 CPA）。大鼠将在具有明显的隔室中接受福尔马林 嗅觉、视觉和触觉线索。每隔一天，他们将接受生理盐水 在第二个隔间里。福尔马林调理后，时间减少 福尔马林相关隔室中的花费将被视为衡量 厌恶。福尔马林诱导CPA对多种中枢神经系统的灭活作用 将研究与伤害感受有关的结构。在第一个实验中， 老鼠会接受一种P物质受体神经毒素，该物质 P-皂草素结合物，在腰椎鞘内空间选择性破坏 I 层脊髓中脑和脊髓丘脑神经元。如果这会降低每次转化费用， 将测试大鼠的损伤或短暂失活的影响 臂旁核以及脊髓丘脑靶核和皮质区域 被有害刺激激活。要研究的丘脑区域包括 腹基底复合体、后丘脑/后层板内组和 中丘脑/板内区域。要研究的皮质区域 包括体感、前扣带回和粒状异常的岛叶皮质。 在补充研究中，皮层区域因失活而与厌恶有关 将使用兴奋性化学试剂来刺激研究以确定是否 在没有外周有害因素的情况下，局部神经元活动可以引发 CPA 刺激。最后，他们将研究福尔马林行为和 CPA 的影响 下行调节系统的可逆失活。