Modulation of cardiac ischemia-sensitive afferent neuron signaling by preemptive C2 spinal cord stimulation: effect on substance P release from rat spinal cord

Modulation of cardiac ischemia-sensitive afferent neuron signaling by preemptive C2 spinal cord stimulation: effect on substance P release from rat spinal cord
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DOI:
10.1152/ajpregu.00544.2007
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发表时间:
2008-01-01
影响因子:
2.8
通讯作者:
Williams, Carole A.
Williams, Carole A.
中科院分区:
医学3区
文献类型:
--
作者:
Ding, XiaoHui;Ardell, Jeffrey L.;Williams, Carole A.

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上颈椎区作为椎管内胸椎反射的控制者,参与缺血心肌的神经元调控。我们的目的是确定当左冠状动脉前降支(CoAO)短暂闭塞激活心肌缺血敏感(交感)传入神经时,大鼠C2颈脊髓(SCS)的刺激是否会改变胸脊髓的输入信号。c-Fos表达的变化被用作脊髓和脑干内神经元激活的指标。P物质(SP)是一种假定的伤害性递质的释放模式,用抗体包被的微探针测量。使用了两种SCS方案:反应性SCS,与间歇CoAO同时应用;先发制人,持续SCS在重复间歇CoAO前15分钟开始并在重复间歇CoAO期间继续使用。CoAO使T4脊髓I和II层的SP释放量高于静息水平。与单独使用CoAO相比,间歇性SCS联合CoAO导致T4中更深层IV-VII的SP释放水平更高。相比之下,在先发制人的持续SCS过程中,CoAO抑制了I和II层的SP释放。与单独使用CoAO相比,先发制人的SCS同样降低了T4脊髓(I-V层)和孤束核中c-Fos的表达,但增加了T4中外侧细胞柱中的表达。这些结果表明,来自高颈区的抢先性SCS调节来自缺血心肌的感觉传入信号。
The upper cervical spinal region functions as an intraspinal controller of thoracic spinal reflexes and contributes to neuronal regulation of the ischemic myocardium. Our objective was to determine whether stimulation of the C2 cervical spinal cord (SCS) of rats modified the input signal at the thoracic spinal cord when cardiac ischemia-sensitive (sympathetic) afferents were activated by transient occlusion of the left anterior descending coronary artery (CoAO). Changes in c-Fos expression were used as an index of neuronal activation within the spinal cord and brain stem. The pattern of substance P (SP) release, a putative nociceptive transmitter, was measured using antibody-coated microprobes. Two SCS protocols were used: reactive SCS, applied concurrently with intermittent CoAO and preemptive, sustained SCS starting 15 min before and continuing during the repeated intermittent CoAO. CoAO increased SP release from laminae I and II in the T4 spinal cord above resting levels. Intermittent SCS with CoAO resulted in greater levels of SP release from deeper laminae IV-VII in T4 than CoAO alone. In contrast, SP release from laminae I and II was inhibited when CoAO was applied during preemptive, sustained SCS. Preemptive SCS likewise reduced c-Fos expression in the T4 spinal cord (laminae I-V) and nucleus tractus solitarius but increased expression in the intermediolateral cell column of T4 compared with CoAO alone. These results suggest that preemptive SCS from the high cervical region modulates sensory afferent signaling from the ischemic myocardium.