嘌呤能受体
神经科学
伤害
背根神经节
伤害感受器
人口
神经传递
钙显像
神经元
刺激
生物
细胞生物学
受体
医学
感觉系统
细胞外
内科学
钙
环境卫生
生物化学
作者
Zhiyong Chen,Qian Huang,Xiaodan Song,Neil B. Ford,Chi Zhang,Qian Xu,Mark C. Lay,Shao Qiu He,Xinzhong Dong,Menachem Hanani,Srinivasa N. Raja
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2021-12-15
卷期号:163 (8): 1636-1647
被引量:7
标识
DOI:10.1097/j.pain.0000000000002556
摘要
In Brief Primary sensory neurons in dorsal root ganglia (DRG) are wrapped by satellite glial cells (SGCs), and neuron-SGC interaction may affect somatosensation, especially nociceptive transmission. P2-purinergic receptors (P2Rs) are key elements in the two-way interactions between DRG neurons and SGCs. However, because the cell types are in such close proximity, conventional approaches such as in vitro culture and electrophysiologic recordings are not adequate to investigate the physiologically relevant responses of these cells at a population level. Here, we performed in vivo calcium imaging to survey the activation of hundreds of DRG neurons in Pirt-GCaMP6s mice and to assess SGC activation in GFAP-GCaMP6s mice in situ. By combining pharmacologic and electrophysiologic techniques, we investigated how ganglionic purinergic signaling initiated by α,β-methyleneadenosine 5′-triphosphate (α,β-MeATP) modulates neuronal activity and excitability at a population level. We found that α,β-MeATP induced robust activation of small neurons—likely nociceptors—through activation of P2X3R. Large neurons, which are likely non-nociceptive, were also activated by α,β-MeATP, but with a delay. Blocking pannexin 1 channels attenuated the late phase response of DRG neurons, indicating that P2R stimulation may subsequently induce paracrine ATP release, which could further activate cells in the ganglion. Moreover, ganglionic α,β-MeATP treatment in vivo sensitized small neurons and enhanced responses of spinal wide-dynamic-range neurons to subsequent C-fiber inputs, suggesting that modulation via ganglionic P2R signaling could significantly affect nociceptive neuron excitability and pain transmission. Therefore, targeting functional P2Rs within ganglia may represent an important new strategy for pain modulation. This in vivo calcium imaging study shows that ganglionic application of α,β-methyleneadenosine 5′-triphosphate activated subpopulations of dorsal root ganglion neurons and satellite glial cells, and induced neuron sensitization.
科研通智能强力驱动
Strongly Powered by AbleSci AI