Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. R01 NS069828
Dev Dyn. 2012 Jan;241(1):16-26. doi: 10.1002/dvdy.22737. Epub 2011 Sep 19.
The word "nociception" is derived from the Latin "nocere," which means "to harm." Nociception refers to the sensory perception of noxious stimuli that have the potential to cause tissue damage. Since the perception of such potentially harmful stimuli often results in behavioral escape responses, nociception provides a protective mechanism that allows an organism to avoid incipient (or further) damage to the tissue. It appears to be universal in metazoans as a variety of escape responses can be observed in both mammalian and non-mammalian vertebrates, as well as diverse invertebrates such as leeches, nematodes, and fruit flies (Sneddon [2004] Brain Research Review 46:123-130; Tobin and Bargmann [2004] Journal of Neurobiology 61:161-174; Smith and Lewin [2009] Journal of Comparative Physiology 195:1089-1106). Several types of stimuli can trigger nociceptive sensory transduction, including noxious heat, noxious chemicals, and harsh mechanical stimulation. Such high-threshold stimuli induce the firing of action potentials in peripheral nociceptors, the sensory neurons specialized for their detection (Basbaum et al. [2009] Cell 139:267-284). In vertebrates, these action potentials can either be relayed directly to a spinal motor neuron to provoke escape behavior (the so-called monosynaptic reflex) or can travel via spinal cord interneurons to higher-order processing centers in the brain. This review will cover the establishment of Drosophila as a system to study various aspects of nociceptive sensory perception. We will cover development of the neurons responsible for detecting noxious stimuli in larvae, the assays used to assess the function(s) of these neurons, and the genes that have been found to be required for both thermal and mechanical nociception. Along the way, we will highlight some of the genetic tools that make the fly such a powerful system for studies of nociception. Finally, we will cover recent studies that introduce new assays employing adult Drosophila to study both chemical and thermal nociception and provide an overview of important unanswered questions in the field.
“伤害感受”一词源自拉丁语“nocere”,意思是“伤害”。伤害感受是指对潜在有害刺激的感觉感知,这些刺激有可能造成组织损伤。由于对这种潜在有害刺激的感知通常会导致行为逃避反应,因此伤害感受提供了一种保护机制,使生物体能够避免组织的初始(或进一步)损伤。它似乎在后生动物中是普遍存在的,因为在哺乳动物和非哺乳动物脊椎动物以及各种无脊椎动物(如水蛭、线虫和果蝇)中都可以观察到各种逃避反应(Sneddon [2004] Brain Research Review 46:123-130; Tobin and Bargmann [2004] Journal of Neurobiology 61:161-174; Smith and Lewin [2009] Journal of Comparative Physiology 195:1089-1106)。几种类型的刺激都可以触发伤害感受感觉转导,包括有害热、有害化学物质和剧烈机械刺激。这种高阈值刺激会在周围伤害感受器(专门用于检测伤害的感觉神经元)中引发动作电位的发射(Basbaum 等人,[2009] Cell 139:267-284)。在脊椎动物中,这些动作电位可以直接传递到脊髓运动神经元,引发逃避行为(所谓的单突触反射),也可以通过脊髓中间神经元传递到大脑中的高级处理中心。本综述将介绍将果蝇建立为研究伤害感受感觉感知各个方面的系统。我们将涵盖幼虫中负责检测有害刺激的神经元的发育、用于评估这些神经元功能的测定法,以及发现对热和机械伤害感受都必需的基因。在此过程中,我们将突出介绍一些使果蝇成为伤害感受研究的强大系统的遗传工具。最后,我们将介绍最近的研究,这些研究引入了利用成年果蝇进行化学和热伤害感受研究的新测定法,并概述了该领域中未解决的重要问题。