Endocannabinoid Modulation of Nociceptive Synapses: Cellular Properties and Functional Role

伤害感受是指动物对疼痛或伤害诱导刺激的感知能力，对动物来说至关重要。的生存。疼痛刺激如何传递到大脑可以由大脑本身改变。 例如，身体的受损区域对随后的刺激变得更加敏感，作为保护身体免受进一步损伤的一种方式。 或者，轻轻摩擦身体的疼痛区域可以暂时减轻疼痛。 该项目的目标是了解调节疼痛刺激传递到大脑的方式的生理过程，重点是内源性大麻素的影响，这是一类已知可以减轻疼痛的神经递质。此外，还将检查某些神经活动模式刺激内源性大麻素递质释放的能力。 本计画将包括行为实验、分子遗传学程序及痛觉神经元（伤害感受器）突触传递的电生理记录。 预期（1）将发现内源性大麻素递质减少伤害性突触信号传导，这将导致疼痛引起的行为减少，以及（2）非疼痛、触敏神经元的激活将刺激内源性大麻素递质的释放，导致疼痛刺激的影响减少。 该项目中的实验对于理解神经生物学的基本过程，大脑如何检测疼痛以及疼痛信号如何通过大脑本身的调节过程改变至关重要。 该提案还为行为、分子遗传学和电生理记录技术方面的研究生和本科生提供了独特的培训机会。 此外，该项目将在联邦资助的科学研究不足的州（南达科他州）和为一些农村和/或第一代大学生服务的机构（南达科他州）进行。

Nociception refers to the ability to detect pain or injury-inducing stimuli, and is critical for an animal?s survival. How painful stimuli are transmitted to the brain can be changed by the brain itself. For example, damaged regions of a body become more sensitive to subsequent stimulation as a way to protect the body from further damage. Alternatively, gently rubbing a painful area of the body can temporarily reduce pain. The goal of this project is to understand the physiological processes that modulate the ways in which painful stimuli are transmitted to the brain, focusing on the effects of endocannabinoids, a class of neurotransmitters known to attenuate pain. In addition, the capacity for certain patterns of neural activity to stimulate the release of endocannabinoid transmitters will be examined. This project will include behavioral experiments, molecular genetic procedures and electrophysiological recordings of synaptic transmission by pain-sensing neurons (nociceptors). It is expected that (1) endocannabinoid transmitters will be found to decrease nociceptive synaptic signaling, which will lead to a decrease in pain-elicited behaviors and (2) that activation of non-pain, touch-sensitive neurons will stimulate the release of endocannabinoid transmitters resulting in a decrease in the effects of painful stimuli. The experiments in this project are critical to developing an understanding of a fundamental process in neurobiology, how the brain detects pain and how pain signaling can be altered by modulatory processes within the brain itself. This proposal also provides unique training opportunities for graduate and undergraduate students in behavioral, molecular genetics and electrophysiological recording techniques. Furthermore, this project will take place in a state (South Dakota) that is under-represented in terms of federally funded scientific research and at an institution (University of South Dakota) that serves a number of rural and/or first generation college students.