Dorsal column and root stimulation at Aβ-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations.
Dorsal column and root stimulation at Aβ-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations.
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DOI：
10.1177/17448069221079559
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发表时间：
2022-01
期刊：
影响因子：
3.3
通讯作者：
Sdrulla AD
中科院分区：
文献类型：
--
作者：
Fan W;Sullivan SJ;Sdrulla AD
神经刺激疗法经常用于患有慢性疼痛的患者。它们来自门控制理论，该理论假设β纤维的激活招募浅背角抑制网络来关闭伤害性信息传递的门，从而达到缓解疼痛的目的。然而，目前的治疗方法的疗效有限，其潜在的回路仍然知之甚少。例如，目前尚不清楚ASDH纤维的持续刺激是否足以驱动β神经元的活动。我们在从小鼠脊髓提取的脊髓中使用多光子显微镜，在谷氨酸和GABA能种群中表达遗传编码的钙指示剂GCaMP6；使用CAIMAN软件从去卷积的钙信号中推断活动水平。持续刺激背柱或背根上的A-β纤维可强烈而短暂地激活这两个群体。在最初的增加之后，谷氨酸能神经元的活动水平下降到基线以下，在刺激停止后，两个群体的活动水平都受到了抑制。令人惊讶的是，只有大约一半的GABA能神经元对Aβ纤维刺激有反应。这一亚组在整个刺激持续时间内表现出活动增加，而无反应者随着时间的推移而减少。我们的发现表明，Aβ纤维刺激最初招募兴奋性和抑制性群体，但对他们的活动有不同的影响，为理解神经刺激装置的镇痛效应提供了基础。观点：这篇文章使用显微镜来描述小鼠脊髓细胞对非痛性神经纤维刺激的反应。这些发现加深了我们对脊髓如何处理信息的理解，并为改进止痛疗法提供了基础。
Neurostimulation therapies are frequently used in patients with chronic pain conditions. They emerged from Gate Control Theory (GCT), which posits that Aβ-fiber activation recruits superficial dorsal horn (SDH) inhibitory networks to “close the gate” on nociceptive transmission, resulting in pain relief. However, the efficacy of current therapies is limited, and the underlying circuits remain poorly understood. For example, it remains unknown whether ongoing stimulation of Aβ-fibers is sufficient to drive activity in SDH neurons. We used multiphoton microscopy in spinal cords extracted from mice expressing the genetically encoded calcium indicator GCaMP6s in glutamatergic and GABAergic populations; activity levels were inferred from deconvolved calcium signals using CaImAn software. Sustained Aβ-fiber stimulation at the dorsal columns or dorsal roots drove robust yet transient activation of both SDH populations. Following the initial increase, activity levels decreased below baseline in glutamatergic neurons and were depressed after stimulation ceased in both populations. Surprisingly, only about half of GABAergic neurons responded to Aβ-fiber stimulation. This subset showed elevated activity for the entire duration of stimulation, while non-responders decreased with time. Our findings suggest that Aβ-fiber stimulation initially recruits both excitatory and inhibitory populations but has divergent effects on their activity, providing a foundation for understanding the analgesic effects of neurostimulation devices. Perspective: This article used microscopy to characterize the responses of mouse spinal cord cells to stimulation of non-painful nerve fibers. These findings deepen our understanding of how the spinal cord processes information and provide a foundation for improving pain-relieving therapies.
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影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
5.5
作者：
Grudt, TJ;Perl, ER
通讯作者：
Perl, ER
影响因子：
16.2
作者：
Grienberger, Christine;Konnerth, Arthur
通讯作者：
Konnerth, Arthur
影响因子：
2.8
作者：
Deer, Timothy;Slavin, Konstantin V.;Wilson, Derron
通讯作者：
Wilson, Derron
影响因子：
3.4
作者：
Chisholm, Kim I.;Khovanov, Nikita;McMahon, Stephen B.
通讯作者：
McMahon, Stephen B.