Neural Circuits Mediating Aversion to Noxious Stimuli

描述(摘自摘要)：与其他感官形式形成对比，如 视觉和听觉，疼痛，从定义上来说，是一开始就令人不快。这 不愉快是逃避和躲避的主观关联性 组织破坏性刺激。尽管这项技术在临床上的重要性 疼痛的情感-动机方面是普遍接受的，缺乏 有效的动物模型阻碍了对其神经生物学基础的研究。这个 这个项目中提出的研究是专门设计来检查 伤害性刺激产生厌恶的神经机制。调查人员 将采用地点偏好装置来测量厌恶的程度 与后爪福尔马林注射相关的上下文(条件位置 厌恶或注册会计师)。大鼠会在一个明显的隔间里接受福尔马林 嗅觉、视觉和触觉提示。每隔一天给他们注射生理盐水 在第二个车厢里。经福尔马林处理后，时间缩短 在福尔马林相关隔间中度过的时间将被视为 厌恶。福尔马林对多种中枢神经系统失活所致CPA的影响 涉及伤害性感受的结构将被研究。在最初的实验中， 大鼠将接受P物质受体神经毒素，该物质 P-皂苷结合物，在腰椎鞘内间隙选择性破坏 板层I、脊髓中脑和脊髓丘脑神经元。如果这降低了注册会计师， 将对大鼠进行损伤或短暂失活的影响测试 臂旁核、脊髓丘脑靶核和皮质区 被有害的刺激激活的。有待研究的丘脑区域包括 腹基底部复合体、丘脑后部/后板内群和 丘脑/板层内侧区。有待研究的皮质区域 包括躯体感觉、前扣带回和颗粒障碍的岛叶皮质。 在互补性研究中，皮层区域因失活而与厌恶有关 研究将使用兴奋性化学试剂进行刺激，以确定是否 在没有外周伤害性刺激的情况下，局部神经元活动可诱发CPA 刺激。最后，他们将研究对福尔马林行为和CPA的影响 下行调节系统的可逆失活。

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.