Tran Emily L, Crawford LaTasha K
Department of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, WI, United States.
Front Cell Neurosci. 2020 Dec 10;14:612982. doi: 10.3389/fncel.2020.612982. eCollection 2020.
Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful. Studies that interrogate uninjured neurons in search of cell-specific mechanisms have shown that nerve injury alters intact, uninjured neurons resulting in an activity that drives stimulus-evoked pain. This review of neuropathic pain mechanisms summarizes cell-type-specific pathology of uninjured sensory neurons and the sensory ganglia that house their cell bodies. Uninjured neurons have demonstrated a wide range of molecular and neurophysiologic changes, many of which are distinct from those detected in injured neurons. These intriguing findings include expression of pain-associated molecules, neurophysiological changes that underlie increased excitability, and evidence that intercellular signaling within sensory ganglia alters uninjured neurons. In addition to well-supported findings, this review also discusses potential mechanisms that remain poorly understood in the context of nerve injury. This review highlights key questions that will advance our understanding of the plasticity of sensory neuron subpopulations and clarify the role of uninjured neurons in developing anti-pain therapies.
尽管对受损神经如何导致慢性疼痛进行了广泛研究，但我们对疼痛机制的理解仍存在重大差距。对于神经损伤引起的疼痛，即神经性疼痛而言尤其如此，在神经性疼痛中，触觉或热刺激会引发疼痛反应，而现有疗法很难对其进行治疗。奇怪的是，这种由刺激引发的疼痛依赖于完整、未受损的感觉神经元，这些神经元会传递最终被感知为疼痛的信号。研究未受损神经元以寻找细胞特异性机制的研究表明，神经损伤会改变完整、未受损的神经元，从而导致驱动刺激诱发疼痛的活动。这篇关于神经性疼痛机制的综述总结了未受损感觉神经元以及容纳其细胞体的感觉神经节的细胞类型特异性病理变化。未受损神经元已表现出广泛的分子和神经生理学变化，其中许多变化与在受损神经元中检测到的变化不同。这些有趣的发现包括疼痛相关分子的表达、兴奋性增加背后的神经生理学变化，以及感觉神经节内细胞间信号传导改变未受损神经元的证据。除了有充分支持的发现外，本综述还讨论了在神经损伤背景下仍了解甚少的潜在机制。本综述强调了一些关键问题，这些问题将推动我们对感觉神经元亚群可塑性的理解，并阐明未受损神经元在开发抗疼痛疗法中的作用。
