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采用模型引导的临床前脊髓刺激评估在体外成年小鼠脊髓中的轴突募集。

Assessment of axonal recruitment using model-guided preclinical spinal cord stimulation in the ex vivo adult mouse spinal cord.

机构信息

Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia.

Department of Physiology, Emory University School of Medicine, Atlanta, Georgia.

出版信息

J Neurophysiol. 2019 Oct 1;122(4):1406-1420. doi: 10.1152/jn.00538.2018. Epub 2019 Jul 24.

DOI:10.1152/jn.00538.2018
PMID:31339796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6843088/
Abstract

Spinal cord stimulation (SCS) is used clinically to limit chronic pain, but fundamental questions remain on the identity of axonal populations recruited. We developed an ex vivo adult mouse spinal cord preparation to assess recruitment following delivery of clinically analogous stimuli determined by downscaling a finite element model of clinical SCS. Analogous electric field distributions were generated with 300-µm × 300-µm electrodes positioned 200 µm above the dorsal column (DC) with stimulation between 50 and 200 µA. We compared axonal recruitment using electrodes of comparable size and stimulus amplitudes when contacting the caudal thoracic DC and at 200 or 600 μm above. Antidromic responses recorded distally from the DC, the adjacent Lissauer tract (LT), and in dorsal roots (DRs) were found to be amplitude and site dependent. Responses in the DC included a unique component not seen in DRs, having the lowest SCS recruitment amplitude and fastest conduction velocity. At 200 μm above, mean cathodic SCS recruitment threshold for axons in DRs and LT were 2.6 and 4.4 times higher, respectively, than DC threshold. SCS recruited primary afferents in all (up to 8) caudal segments sampled. Whereas A and C fibers could be recruited at nearby segments, only A fiber recruitment and synaptically mediated dorsal root reflexes were observed in more distant (lumbar) segments. In sum, clinically analogous SCS led to multisegmental recruitment of several somatosensory-encoding axonal populations. Most striking is the possibility that the lowest threshold recruitment of a nonprimary afferent population in the DC are postsynaptic dorsal column tract cells (PSDCs) projecting to gracile nuclei. Spinal cord stimulation (SCS) is used clinically to control pain. To identify axonal populations recruited, finite element modeling identified scaling parameters to deliver clinically analogous SCS in an ex vivo adult mouse spinal cord preparation. Results showed that SCS first recruited an axonal population in the dorsal column at a threshold severalfold lower than primary afferents. These putative postsynaptic dorsal column tract cells may represent a previously unconsidered population responsible for SCS-induced paresthesias necessary for analgesia.

摘要

脊髓刺激 (SCS) 临床上用于限制慢性疼痛,但对于募集的轴突群体的身份仍存在基本问题。我们开发了一种离体成年小鼠脊髓制备物,以评估通过缩小临床 SCS 的有限元模型来传递类似临床刺激时的募集情况。使用 300µm×300µm 的电极在背柱 (DC) 上方 200µm 处产生类似的电场分布,刺激电流在 50-200µA 之间。我们比较了在接触胸段 DC 时使用类似大小的电极和刺激幅度以及在 200µm 或 600µm 上方时的轴突募集情况。从 DC 远端记录的逆行反应、相邻的 Lissauer 束 (LT) 和背根 (DR) 中发现,反应幅度和部位均存在依赖性。DC 中的反应包括在 DR 中未见的独特成分,其 SCS 募集幅度最低,传导速度最快。在 200µm 上方,DR 和 LT 中轴突的阴极 SCS 募集阈值分别比 DC 阈值高 2.6 倍和 4.4 倍。SCS 募集了所有 (多达 8) 取样的尾部节段中的初级传入纤维。虽然 A 和 C 纤维可以在附近的节段募集,但只有 A 纤维募集和突触介导的背根反射在更远的 (腰椎) 节段观察到。总之,类似临床的 SCS 导致了几个感觉编码轴突群体的多节段募集。最引人注目的是,在 DC 中募集非初级传入群体的最低阈值可能是投射到薄束核的突触后背柱束细胞 (PSDCs)。脊髓刺激 (SCS) 临床上用于控制疼痛。为了识别募集的轴突群体,有限元建模确定了缩放参数,以在离体成年小鼠脊髓制备物中传递类似临床的 SCS。结果表明,SCS 首先在阈值比初级传入纤维低几倍的背柱中募集了一个轴突群体。这些假定的突触后背柱束细胞可能代表了以前未被考虑的群体,负责 SCS 诱导的刺痛感,这是镇痛所必需的。

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