Spencer Nick J, Hibberd Tim, Xie Zili, Hu Hongzhen
Visceral Neurophysiology Laboratory, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, Australia.
Department of Anesthesiology, The Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO, United States.
Front Neurosci. 2022 Dec 19;16:1096405. doi: 10.3389/fnins.2022.1096405. eCollection 2022.
In the past few years, there has been extraordinary interest in how the gut communicates with the brain. This is because substantial and gathering data has emerged to suggest that sensory nerve pathways between the gut and brain may contribute much more widely in heath and disease, than was originally presumed. In the skin, the different types of sensory nerve endings have been thoroughly characterized, including the morphology of different nerve endings and the sensory modalities they encode. This knowledge is lacking for most types of visceral afferents, particularly spinal afferents that innervate abdominal organs, like the gut. In fact, only recently have the nerve endings of spinal afferents in any visceral organ been identified. What is clear is that spinal afferents play the major role in pain perception from the gut to the brain. Perhaps surprisingly, the majority of spinal afferent nerve endings in the gut express the ion channel TRPV1, which is often considered to be a marker of "nociceptive" neurons. And, a majority of gut-projecting spinal afferent neurons expressing TRPV1 are activated at low thresholds, in the "normal" physiological range, well below the normal threshold for detection of painful sensations. This introduces a major conundrum regarding visceral nociception. How should we define a "nociceptor" in the gut? We discuss the notion that nociception from the gut wall maybe a process encrypted into multiple different morphological types of spinal afferent nerve ending, rather than a single class of sensory ending, like free-endings, suggested to underlie nociception in skin.
在过去几年里，人们对肠道与大脑之间的沟通方式产生了极大的兴趣。这是因为大量且不断积累的数据表明，肠道与大脑之间的感觉神经通路在健康和疾病中的作用可能比最初设想的要广泛得多。在皮肤中，不同类型的感觉神经末梢已被充分表征，包括不同神经末梢的形态以及它们所编码的感觉模式。而对于大多数类型的内脏传入神经，尤其是支配腹部器官（如肠道）的脊髓传入神经，我们还缺乏这方面的知识。事实上，直到最近才确定了任何内脏器官中脊髓传入神经的神经末梢。很明显，脊髓传入神经在从肠道到大脑的疼痛感知中起主要作用。也许令人惊讶的是，肠道中大多数脊髓传入神经末梢都表达离子通道TRPV1，而TRPV1通常被认为是“伤害性”神经元的标志物。而且，大多数表达TRPV1的投射到肠道的脊髓传入神经元在低阈值下被激活，处于“正常”生理范围内，远低于检测疼痛感觉的正常阈值。这就引发了一个关于内脏伤害感受的重大难题。我们应该如何定义肠道中的“伤害感受器”呢？我们讨论了这样一种观点，即来自肠壁的伤害感受可能是一个编码到多种不同形态类型的脊髓传入神经末梢中的过程，而不是像皮肤中被认为是伤害感受基础的单一类别的感觉末梢（如游离末梢）。
