Opioids and Spinal Nociceptive Transmission

描述(申请人提供)：这位被指导的临床科学家 发展奖将为候选人提供必要的资源 发展一种新的方法来研究阿片类药物在调制中的作用 伤害性感受。候选人目前的研究涉及阿片类药物的检查 隔离系统中伤害性初级传入神经元的作用。这 研究项目将扩大到包括伤害性感受器的研究 在脊髓内的传播。 伤害性刺激激活伤害性初级传入神经元，形成 兴奋性突触与次级伤害性神经元的联系 脊髓背角的清晰区域。这个伤害性信号是 由兴奋性和抑制性输入调制，然后从 脊髓通向更高的区域。目前还不清楚这条途径是如何进行的，以及在哪里进行。 阿片类药物起到止痛的作用。中描述的实验的目标 这个建议是：1)确定阿片类药物是否抑制兴奋性突触 伤害性神经元的反应，增强抑制反应，或两者兼而有之；2) 评价突触前和突触后抑制的生理学相关性 阿片类药物的机制；以及3)确定阿片类药物如何影响脑内神经元。 脊髓伤害性感受通路的不同部分。 拟用于上述实验的模型系统为体外实验大鼠 脊髓切片制备。这些实验所需的技术 要求很高，需要大量的培训才能掌握。在……里面 此外，脊髓神经回路和突触生理学的知识将 在这一新的研究领域获得专业知识是必要的。这些目标将是 主要通过在脊柱方面经验丰富的研究人员的密切指导实现 脐带片生理学。与其他调查人员定期举行会议 麻醉学系和神经科学中心 在突触生理学方面的经验将提供有价值的互动和 学习的机会。此外，讲课、研讨会和领导 研究生集中讨论脊髓伤害性感受性话题 传播将促进职业发展。实现这些目标将 允许候选人建立独立的科学研究计划 成功的学术生涯结合了研究、教学和临床护理。

DESCRIPTION (provided by applicant): This Mentored Clinical Scientist Development Award will provide the candidate with resources necessary to develop a new approach to study the role of opioids in the modulation of nociception. The candidate's current research involves examination of opioid actions on nociceptive primary afferent neurons in an isolated system. This research program will be broadened to include the study of nociceptive transmission within the spinal cord. Noxious stimuli activate nociceptive primary afferent neurons, which form excitatory synaptic connections with secondary nociceptive neurons in several well-defined areas of the spinal dorsal horn. This nociceptive signal is modulated by both excitatory and inhibitory inputs and then relayed from the spinal cord to higher areas. It is unclear how and where in this pathway opioids act to produce analgesia. The goals of the experiments described in this proposal are: 1) to determine whether opioids depress excitatory synaptic responses of nociceptive neurons, augment inhibitory responses, or both; 2) to evaluate the physiologic relevance of presynaptic and postsynaptic inhibitory mechanisms of opioids; and 3) to determine how opioids affect neurons in different parts of the spinal nociceptive pathway. The model system to be used for the proposed experiments is the in vitro rat spinal cord slice preparation. The techniques required for these experiments are demanding and require a significant amount of training to master. In addition, a knowledge of spinal neuronal circuitry and synaptic physiology will be needed to obtain expertise in this new field of study. These goals will be achieved primarily by close mentoring by an investigator experienced in spinal cord slice physiology. Regular meetings with other investigators in the department of Anesthesiology and the Center for Neuroscience who are experienced in synaptic physiology will provide valuable interactions and opportunities for learning. In addition, giving lectures, seminars, and leading graduate students in intensive discussions on topics in spinal nociceptive transmission will enhance career development. Achievement of these goals will allow the candidate to establish an independent scientific research program and a successful academic career combining research, teaching, and clinical care.