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，伤害性刺激的皮质处理是导致疼痛的更复杂、非反射性和临床相关方面的原因。人类成像研究证明了特定皮质区域在伤害感受中的重要性，特别是岛叶皮质。目前，皮层参与伤害感受处理的神经回路仍然很大程度上未知。我们之前已经确定了大鼠岛叶皮质内的一个区域，即头端无颗粒岛叶皮质（RAIC），该区域参与疼痛行为的调节。该提案研究了 RAIC 介导的抗伤害作用中涉及的神经机制。我们最近的工作表明，阻断接受密集多巴胺能神经支配的 RAIC 中的多巴胺再摄取，可以产生持续的行为镇痛作用并抑制脊髓伤害性区域的细胞活动。作为这些研究的延续，本提案的目的旨在测试以下具体假设：（1）减少 RAIC 中的多巴胺抑制会增加大脑伤害性区域的细胞活动； (2) RAIC 中多巴胺介导的抗伤害作用涉及 GABA 能神经传递； (3) 丘脑传入神经直接控制 RAIC 中多巴胺的释放；最后，(4) 多巴胺负责儿茶酚胺在 RAIC 中的抗伤害作用，与去甲肾上腺素能传递无关。本提案将从 RAIC 中识别参与多巴胺抗伤害作用的神经回路。虽然多巴胺在前脑中的作用已成为与情绪障碍和退行性疾病相关的广泛研究的主题，但本提案首次研究了皮质多巴胺能神经传递在伤害感受中的参与。大脑皮层多巴胺能抑制丧失的临床影响包括中枢性疼痛综合征，例如帕金森病和接受精神安定药物治疗的患者中报道的疼痛综合征。