Plasticity and Modulation in Models of Persistent Pain

持续性疼痛模型的可塑性和调节

• 批准号: 6419044
• 负责人: RONALD DUBNER
• 金额: $ 133.96万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6419044
• 关键词: analgesia; chronic pain; neural plasticity

Pain is the major patient complaint with systemic illness, traumatic injuries and surgery. The last decade has resulted in new knowledge that is leading to significant improvements in the management of persistent pain. Nevertheless, important gaps in our understanding remain. Many difficult to treat persistent pains involve deep visceral and muscle tissue. Research on the development of nociceptive systems is minimal as the effect of early infant persistent injury is limited above the level of the brain stem, yet multiple forebrain structures participate in the perception of pain. The major theme of this program project is the study of modulatory influences in nociceptive circuitry in response to persistent visceral and cutaneous tissue injury and the effect of neonatal exposure to pain on such plasticity. The individual projects all take advantage of the development of new animal models of inflammation and examine the changes that take place in primary afferent neurons, dorsal horn circuitry and descending modulatory pathways in adults after injury and the impact of neonatal injury on these changes. Project #1 will study the changes in dorsal horn excitability that take place after cholonic inflammation in the rat and how descending modulatory mechanisms contribute to the sensitization process. Project #2 will focus on the role of early postnatal pain experience as a risk factor for the development of nociceptive systems and the neurochemical reorganization of dorsal root ganglia neurons and spinal dorsal horn neurons. Project #3 will study the modulation of primary afferent excitability and their underlying biophysical properties after inflammation in the adult and the effect of neonatal injury on these changes. Project #4 will examine the influence of forebrain structures on descending modulatory effects in a rat model of cutaneous inflammation and the effects of neonatal cutaneous and visceral pain experience on these descending circuits. Project #5 will use a model of inflammatory hyperalgesia systems in these effects, and the neuroprotective role of gustatory stimulation in preventing developmental changes in nociceptive circuitry produced by neonatal injury. In summary, this program project grant brings together a group of experts in the field of pain to study the role of neuronal modulation in animal models of persistent pain.

疼痛是全身性疾病，创伤性伤害和手术的主要患者抱怨。最近十年导致了新的知识，从而导致持续疼痛的管理有了重大改善。然而，我们理解的重要差距仍然存在。许多难以治疗持续的疼痛涉及深内脏和肌肉组织。关于伤害性系统发展的研究很少，因为早期婴儿持续损伤的作用受到脑干水平的限制，但是多个前脑结构参与了疼痛的感知。该计划项目的主要主题是研究对持续性内脏和皮肤组织损伤的调节性影响，以及新生儿暴露于这种可塑性对疼痛的影响。各个项目都利用了新的炎症动物模型的发展，并检查了原发性传入神经元，背喇叭回路和成人损伤后成人的调节途径的变化以及新生儿损伤对这些变化的影响。项目＃1将研究大鼠胆碱炎症后发生的背角兴奋性的变化，以及降低的调节机制如何有助于敏化过程。项目＃2将重点介绍早期产后疼痛经验作为伤害性系统发展的危险因素以及背根神经元和脊髓背角神经元的神经化学重组的危险因素。项目＃3将研究成人炎症后的主要传入兴奋性及其潜在的生物物理特性的调节以及新生儿损伤对这些变化的影响。项目＃4将检查前脑结构对皮肤炎症大鼠模型下降调节作用的影响，以及新生儿皮肤和内脏疼痛经历对这些下降电路的影响。项目＃5将在这些作用中使用炎症性痛觉系统模型，以及味觉刺激在预防新生儿损伤产生的伤害感受电路的发育变化中的神经保护作用。总而言之，该计划项目Grant汇集了一群疼痛领域的专家，以研究神经元调节在持续性疼痛模型中的作用。