Sun Linlin, Chen Chao, Xiang Xuwu, Guo Shengyang, Yang Guang
Department of Anesthesiology, Columbia University Medical Center, New York, NY, United States.
Department of Physiology and Neuroscience, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, United States.
Front Neurosci. 2024 Apr 16;18:1368507. doi: 10.3389/fnins.2024.1368507. eCollection 2024.
Peripheral sensory neurons serve as the initial responders to the external environment. How these neurons react to different sensory stimuli, such as mechanical or thermal forces applied to the skin, remains unclear.
Using two-photon Ca imaging in the lumbar 4 dorsal root ganglion (DRG) of awake -GCaMP6s mice, we assessed neuronal responses to various mechanical (punctate or dynamic) and thermal forces (heat or cold) sequentially applied to the paw plantar surface.
Our data indicate that in normal awake male mice, approximately 14 and 38% of DRG neurons respond to either single or multiple modalities of stimulation. Anesthesia substantially reduces the number of responsive neurons but does not alter the ratio of cells exhibiting single-modal responses versus multi-modal responses. Following peripheral nerve injury, DRG cells exhibit a more than 5.1-fold increase in spontaneous neuronal activity and a 1.5-fold increase in sensory stimulus-evoked activity. As neuropathic pain resulting from nerve injury progresses, the polymodal nature of sensory neurons intensifies. The polymodal population increases from 39.1 to 56.9%, while the modality-specific population decreases from 14.7 to 5.0% within a period of 5 days.
Our study underscores polymodality as a significant characteristic of primary sensory neurons, which becomes more pronounced during the development of neuropathic pain.
外周感觉神经元是对外部环境的初始应答者。这些神经元如何对不同的感觉刺激做出反应，例如施加于皮肤的机械力或热力，仍不清楚。
我们使用清醒的表达绿色荧光钙蛋白6s（GCaMP6s）的小鼠腰4背根神经节（DRG）中的双光子钙成像技术，依次评估神经元对施加于爪足底表面的各种机械力（点状或动态）和热力（热或冷）的反应。
我们的数据表明，在正常清醒雄性小鼠中，约14%和38%的DRG神经元对单一或多种刺激模式有反应。麻醉会大幅减少有反应的神经元数量，但不会改变表现出单模式反应与多模式反应的细胞比例。外周神经损伤后，DRG细胞的自发神经元活动增加超过5.1倍，感觉刺激诱发的活动增加1.5倍。随着神经损伤导致的神经性疼痛进展，感觉神经元的多模式特性增强。在5天内，多模式群体从39.1%增加到56.9%，而模式特异性群体从14.7%减少到5.0%。
我们的研究强调多模式是初级感觉神经元的一个重要特征，在神经性疼痛发展过程中变得更加明显。
