CORTICAL MODULATION OF PAIN BEHAVIOR

疼痛行为的皮质调节

• 批准号: 6477360
• 负责人: LUC JASMIN
• 金额: $ 12.72万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-10 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6477360
• 关键词: GABA aminotransferase; amygdala; analgesia; behavior; behavior test; behavioral /social science research tag; catecholamines; cerebral cortex; chronic pain; dopamine; dorsal raphe nucleus; electron microscopy; experimental brain lesion; gamma aminobutyrate; glutamate receptor; hypothalamus; laboratory rat; molecular psychobiology; norepinephrine; parabrachial nucleus; prosencephalon; protooncogene; solitary tract nucleus; stereotaxic techniques; thalamic nuclei

It is generally agreed that cortical processing of nociceptive stimuli is responsible for the more complex, non-reflexive, and clinically relevant aspects of pain. Human imaging studies are demonstrating the importance of specific cortical areas in nociception, the insular cortex in particular. Presently the neural circuits through which the cortex is involved in nociceptive processing remain largely unknown. We have previous identified a region within the insular cortex of the rat, the rostral agranular insular cortex (RAIC), which is involved in modulation of pain behavior. This proposal examines the neural mechanisms involved in RAIC mediated antinociception. Our most recent work has demonstrated that blocking dopamine reuptake in the RAIC, which receives dense dopaminergic innervation, produces sustained behavioral antinociception and inhibition of cell activity in nociceptive areas of the spinal cord. As a continuation of these studies, the aims of the present proposal are designed to test the following specific hypotheses: (1) that decreasing dopamine inhibition in the RAIC increases cellular activity in nociceptive areas of the brain; (2) that dopamine mediated antinociception in the RAIC involves GABAergic neurotransmission; (3) that thalamic afferents directly control the release of dopamine in the RAIC; and finally, (4) that dopamine is responsible for the antinociceptive effect of catecholamines in the RAIC independently of noradrenergic transmission. The present proposal will identify neural circuits involved in dopamine antinociception from the RAIC. While the role of dopamine in the forebrain has been the subject of extensive research in relatio9n to mood disorders and degenerative diseases, the present proposal is the first to examine the involvement of cortical dopaminergic neurotransmission in nociception. The clinical implications of loss of dopaminergic inhibition of the cerebral cortex include central pain syndromes such as those reported in Parkinson's disease and in patients treated with neuroleptic drugs.

人们普遍认为，伤害性刺激的皮质加工是疼痛的更复杂，非反射和临床相关方面的原因。人类成像研究表明，特定皮质区域在伤害感受中的重要性，尤其是岛状皮质。目前，皮质与伤害性处理的神经回路仍然很大未知。我们以前已经确定了大鼠岛状皮质内的一个区域，即the骨造成的岛状皮质（RAIC），该区域参与了疼痛行为的调节。该提案检查了与Raic介导的抗伤害感受有关的神经机制。我们的最新工作表明，受到密集多巴胺能神经神经的RAIC中的多巴胺再摄取会产生持续的行为抗伤害感受和抑制脊髓伤害性区域的细胞活性。作为这些研究的延续，本提案的目的旨在检验以下特定假设：（1）降低RAIC中多巴胺抑制的抑制作用会增加大脑伤害感受性区域的细胞活性； （2）多巴胺介导的RAIC中的抗伤害感受涉及GABA能神经传递； （3）丘脑传入直接控制了多巴胺在RAIC中的释放；最后，（4）多巴胺是造成儿茶酚胺在RAIC中独立于去甲肾上腺素能传播的抗伤害感受效应的。本提案将确定来自RAIC的多巴胺抗伤害感受的神经回路。虽然多巴胺在前脑中的作用一直是对情绪障碍和退行性疾病的广泛研究的主题，但目前的提案是第一个研究皮质多巴胺能神经传递在伤害感受中的参与。多巴胺能抑制大脑皮层的临床意义包括中枢疼痛综合征，例如帕金森氏病中报道的综合症和接受神经摄影药物治疗的患者。