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.

尽管已经广泛研究了受伤的神经如何导致慢性疼痛，但在我们对疼痛机制的理解上仍存在重大差距。对于由神经损伤或神经性疼痛引起的疼痛尤其如此，其中触觉或热刺激引起疼痛反应，这特别难于用现有疗法治疗。奇怪的是，这种由刺激引起的疼痛依赖于完整无损的感觉神经元，这些神经元传递的信号最终被感觉为疼痛。研究未损伤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的未损伤神经元，从而导致引起刺激性疼痛的活动。这篇关于神经性疼痛机制的综述总结了未受伤的感觉神经元和容纳其细胞体的感觉神经节的细胞类型特异性病理学。未受伤的神经元已表现出广泛的分子和神经生理学变化，其中许多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，增加兴奋性的神经生理学变化，以及感觉神经节内细胞间信号改变未损伤神经元的证据。除了得到充分支持的发现外，本综述还讨论了在神经损伤的情况下仍知之甚少的潜在机制。