Department of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, WI, USA, Madison, WI, USA.
Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Toxicol Pathol. 2020 Jan;48(1):174-189. doi: 10.1177/0192623319869011. Epub 2019 Sep 25.
The simple tripartite classification of sensory neurons as A-beta, A-delta, and C fibers fails to convey the complexity of the neurons that encode stimuli as diverse as the texture of a surface, the location of a pinprick, or the direction of hair movement as a breeze moves across the skin. It has also proven to be inadequate when investigating the molecular mechanisms underlying pain, which can encompass any combination of chemical, tactile, and thermal modalities. Beginning with a brief overview of visceral and sensory neuroanatomy, this review expands upon sensory innervation of the skin as a prime example of the heterogeneity and complexity of the somatosensory nervous system. Neuroscientists have characterized defining features of over 15 subtypes of sensory neurons that innervate the skin of the mouse. This has enabled the study of cell-specific mechanisms of pain, which suggests that diverse sensory neuron subtypes may have distinct susceptibilities to toxic injury and different roles in pathologic mechanisms underlying altered sensation. Leveraging this growing body of knowledge for preclinical trials and models of neurotoxicity can vastly improve our understanding of peripheral nervous system dysfunction, advancing the fields of toxicologic pathology and neuropathology alike.
简单的将感觉神经元分为 A-β、A-δ 和 C 纤维的三分法,无法传达出编码各种刺激的神经元的复杂性,这些刺激包括表面质地、刺痛位置或微风拂过皮肤时毛发的运动方向。当研究疼痛的分子机制时,这种分类法也被证明是不够的,因为疼痛可能包括化学、触觉和热觉等任何组合形式。本文从内脏和感觉神经解剖学的简要概述开始,扩展到皮肤的感觉神经支配,以此作为躯体感觉神经系统异质性和复杂性的主要范例。神经科学家已经确定了超过 15 种感觉神经元亚型的定义特征,这些神经元支配着小鼠的皮肤。这使得对疼痛的细胞特异性机制的研究成为可能,这表明不同的感觉神经元亚型可能对毒性损伤具有不同的易感性,并且在改变感觉的病理机制中可能具有不同的作用。利用这一日益增长的知识,进行临床前试验和神经毒性模型的研究,可以极大地提高我们对周围神经系统功能障碍的理解,从而推动毒理学病理学和神经病理学领域的发展。