Degeneration of Myelinated Efferent Fibers Induces Spontaneous Activity in Uninjured C-Fiber Afferents
Degeneration of Myelinated Efferent Fibers Induces Spontaneous Activity in Uninjured C-Fiber Afferents
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DOI：
10.1523/jneurosci.22-17-07746.2002
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发表时间：
2002-09
期刊：
影响因子：
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通讯作者：
Gang Wu;M. Ringkamp;B. Murinson;E. Pogatzki;T. Hartke;Himali M. Weerahandi;J. Campbell;J. Griffin-J.-Gr
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文献类型：
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作者：
Gang Wu;M. Ringkamp;B. Murinson;E. Pogatzki;T. Hartke;Himali M. Weerahandi;J. Campbell;J. Griffin-J.-Gr
我们最近证明，L5 脊神经横断后，L4 脊神经中未受伤的 C 纤维伤害感受器会产生自发活动。我们假设华勒变性导致来自邻近脊神经的邻近未受伤传入神经的特性发生改变。为了探讨有髓鞘纤维与无髓鞘纤维变性的作用，我们研究了大鼠 L5 腹侧神经根切断术的效果。这种病变主要导致有髓纤维的变性。使用 von Frey 毛发评估机械缩爪阈值，并使用梳理纤维技术记录 L4 脊神经中的单个 C 纤维传入。以盲法收集行为和电生理学数据。手术后 7 天，腹侧神经根切断术后观察到退缩阈值显着降低，但假手术后未观察到。单纤维记录显示，损伤后 8-10 天，25% 的 C 纤维传入神经出现低频自发活动，而假手术后只有 11%。缩爪阈值与高阈值 C 纤维传入的自发活动的发生率呈负相关。在正常动物中，对 C 纤维而非 A 纤维进行低频电刺激，强度会产生爪子继发性机械痛觉过敏的行为症状。这些结果表明有髓传出纤维的变性足以诱导 C 纤维传入纤维的自发活动和机械痛觉过敏的行为迹象。神经性疼痛行为的发展不需要来自受伤传入神经的异位自发活动。这些结果为华勒变性在神经性疼痛中的作用提供了额外的证据。
We demonstrated recently that uninjured C-fiber nociceptors in the L4 spinal nerve develop spontaneous activity after transection of the L5 spinal nerve. We postulated that Wallerian degeneration leads to an alteration in the properties of the neighboring, uninjured afferents from adjacent spinal nerves. To explore the role of degeneration of myelinated versus unmyelinated fibers, we investigated the effects of an L5 ventral rhizotomy in rat. This lesion leads to degeneration predominantly in myelinated fibers. Mechanical paw-withdrawal thresholds were assessed with von Frey hairs, and teased-fiber techniques were used to record from single C-fiber afferents in the L4 spinal nerve. Behavioral and electrophysiological data were collected in a blinded manner. Seven days after surgery, a marked decrease in withdrawal thresholds was observed after the ventral rhizotomy but not after the sham operation. Single fiber recordings revealed low-frequency spontaneous activity in 25% of the C-fiber afferents 8–10 d after the lesion compared with only 11% after sham operation. Paw-withdrawal thresholds were inversely correlated with the incidence of spontaneous activity in high-threshold C-fiber afferents. In normal animals, low-frequency electrocutaneous stimulation at C-fiber, but not A-fiber, strength produced behavioral signs of secondary mechanical hyperalgesia on the paw. These results suggest that degeneration in myelinated efferent fibers is sufficient to induce spontaneous activity in C-fiber afferents and behavioral signs of mechanical hyperalgesia. Ectopic spontaneous activity from injured afferents was not required for the development of the neuropathic pain behavior. These results provide additional evidence for a role of Wallerian degeneration in neuropathic pain.