Brainstem Control of Pain Transmission

脑干控制疼痛传播

• 批准号: 7483320
• 负责人: Allan I. Basbaum
• 金额: $ 6.51万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7483320
• 关键词: Acute; Adult; Afferent Neurons; Animals; Axon; Bacterial Artificial Chromosomes; Brain; Brain Stem; Brain region; Caliber; Cell Nucleus; Class; Complex; Condition; Development; Distant; Estrogen Receptors; Excision; Genetic Recombination; Germ; Hyperalgesia; Immediate-Early Genes; Inflammation; Injection of therapeutic agent; Injury; Interneurons; JUN gene; Knock-in Mouse; Label; LacZ Genes; Lectin; Leg; Mediating; Methods; Modification; Mus; Nature; Neurons; Nociception; Nociceptors; Numbers; Pain; Pain management; Peripheral; Peripheral nerve injury; Persistent pain; Physiological; Posterior Horn Cells; Process; Property; Research Personnel; Resistance; Site; Spinal Cord; Spinal Ganglia; Spinal cord posterior horn; Structure of trigeminal ganglion; Substance P; Tamoxifen; Time; Tissues; Tracer; Transgenes; Transgenic Mice; Transgenic Organisms; Wheat; Wheat Germ Agglutinins; allodynia; anterograde transport; central sensitization; dorsal horn; injured; nerve injury; novel; peripherin; programs; promoter; recombinase; research study; response; transmission process; vector

The development of persistent pain conditions in the setting of tissue or nerve injury results to a great extent from significant reorganization of CNS circuits. These changes contribute to a central sensitization/hyperexcitability state that underlies allodynia and hyperalgesia, the hallmarks of persistent pain conditions. Many studies have focused on the injury-induced sprouting of primary afferents and on the physiological properties of altered "pain" response neurons in the spinal cord dorsal horn, but there is little information about the tissue and nerve-injury-induced local and long distant circuit changes that occur, in the spinal cord and at more rostral sites. Recently, we developed a transgenic mouse in which wheat germ agluttinin (WGA) synthesis, anterograde transport and transneuronal labeling of complex circuits can be triggered from neurons in any region of the brain or spinal cord, during development or in the adult. In the present proposal, we will use these mice and others that we will generate to study the development and adult organization of CNS circuits engaged by small diameter primary afferent nociceptors and to study their modifications after tissue or nerve injury. Through a highly novel modification of this transneuronal tracing method, in which the tracer is induced in primary afferent neurons only if their peripheral axon has been transected, we also propose to study nerve injury-induced reorganization of CNS nociceptive circuits. Both the normal circuits and the reorganization of circuits engaged by small and large diameter axons will be studied in these experiments. Finally, through the development of BAC transgenics, we propose to begin a detailed analysis of the circuits that arise from neurochemically distinct primary afferent nociceptors. Taken together, these studies will provide an entirely new anatomical perspective on the circuits that process the nociceptive messages resulting in acute and persistent pain.

在组织或神经损伤的情况下出现持续性疼痛会导致严重的后果。 中枢神经系统回路的重大重组的程度。这些变化有助于中央 过敏/过度兴奋状态是异常性疼痛和痛觉过敏的基础，是持续性疼痛的标志 疼痛情况。许多研究都集中在损伤引起的初级传入神经萌芽和 脊髓背角“疼痛”反应神经元的生理特性发生改变，但几乎没有 有关组织和神经损伤引起的局部和远距离电路变化的信息， 脊髓和更多的吻端部位。最近，我们开发了一种转基因小鼠，其中小麦胚芽 凝集素 (WGA) 合成、顺行转运和复杂回路的跨神经元标记可以 在发育期间或成人中，由大脑或脊髓任何区域的神经元触发。在 目前的建议，我们将使用这些小鼠和我们将产生的其他小鼠来研究发育和 由小直径初级传入伤害感受器参与的中枢神经系统回路的成人组织并进行研究 组织或神经损伤后它们的改变。通过对这种跨神经元的高度新颖的修饰 追踪方法，其中只有当初级传入神经元的外周轴突具有 被横断后，我们还建议研究神经损伤引起的中枢神经系统伤害性回路的重组。 正常回路和小直径轴突和大直径轴突参与的回路重组都将 在这些实验中进行研究。最后，通过 BAC 转基因技术的发展，我们建议 开始对由神经化学上不同的初级传入神经产生的回路进行详细分析 伤害感受器。总而言之，这些研究将为研究提供一个全新的解剖学视角。 处理导致急性和持续性疼痛的伤害性信息的电路。