Dorsal root ganglia control nociceptive input to the central nervous system.

Dorsal root ganglia control nociceptive input to the central nervous system.
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DOI:
10.1371/journal.pbio.3001958
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发表时间:
2023-01
期刊:
影响因子:
9.8
通讯作者:
--
中科院分区:
生物学1区
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--
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越来越多的观察表明,外周体感神经节可能调节伤害性信息的传递,但直接证据很少。在大鼠和小鼠的实验中,我们发现外周传入的伤害性信息在背根神经节(DRG)内经历了动态过滤,并认为这种过滤发生在轴突分叉(T形连接)。利用感觉神经元(脊神经和背根)的外周和中枢突起的同步电生理记录、GABA能神经前体细胞的神经节移植和光遗传学,我们证明了通过DRG的动作电位的张力性和动态过滤的存在。局部应用GABA或从DRG移植的GABA能前体细胞中释放GABA所诱导的滤过是针对伤害性纤维的。光片成像和计算机模拟表明,与其他类型的体感纤维相比,伤害性感受器的干轴突更短,这使得躯体对T形连接过滤的控制更有效。光遗传诱导移植的GABA能细胞在DRG内释放GABA,增强了滤过性,并减轻了体内慢性炎症和神经病理性损伤所产生的伤害性刺激的超敏反应。这些发现支持DRGs对疼痛信息的“门控”,并为疼痛缓解提出了新的治疗方法。在背根神经节(DRG),沿着外周躯体感觉神经传递的信息可以被主动地修改。这项研究证明了强直的和动态的GABA能过滤通过DRG的动作电位的存在,具有缓解疼痛的治疗意义。
Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support “gating” of pain information by DRGs and suggest new therapeutic approaches for pain relief. Information transmitted along the peripheral somatosensory nerves can be actively modified at the dorsal root ganglion (DRG). This study demonstrates the existence of tonic and dynamic GABAergic filtering of action potentials traveling through the DRG, with therapeutic implications for pain relief.
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