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ARTICLE, Behavioral/Systems

Degeneration of Myelinated Efferent Fibers Induces Spontaneous Activity in Uninjured C-Fiber Afferents

Gang Wu, Matthias Ringkamp, Beth B. Murinson, Esther M. Pogatzki, Timothy V. Hartke, Himali M. Weerahandi, James N. Campbell, John W. Griffin and Richard A. Meyer
Journal of Neuroscience 1 September 2002, 22 (17) 7746-7753; DOI: https://doi.org/10.1523/JNEUROSCI.22-17-07746.2002
Gang Wu
1Departments of Neurosurgery,
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Matthias Ringkamp
1Departments of Neurosurgery,
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Beth B. Murinson
2Neurology, and
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Esther M. Pogatzki
1Departments of Neurosurgery,
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Timothy V. Hartke
1Departments of Neurosurgery,
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Himali M. Weerahandi
1Departments of Neurosurgery,
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James N. Campbell
1Departments of Neurosurgery,
4Applied Physics Laboratory, Johns Hopkins University, Baltimore, Maryland 21287
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John W. Griffin
2Neurology, and
3Neuroscience, and the
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Richard A. Meyer
1Departments of Neurosurgery,
4Applied Physics Laboratory, Johns Hopkins University, Baltimore, Maryland 21287
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    Fig. 1.

    Spontaneous activity in two typical C-fiber afferents recorded 8 d after an L5 ventral rhizotomy.A, Teased-fiber techniques were used to record activity from single nerve fibers of the L4 spinal nerve (R) in sham-operated animals and in animals after transection of the L5 ventral root (T). Electrical stimulation of the sciatic nerve (S) was used to identify and count the number of C-fibers at the recording electrode. B, The presence of spontaneous action potential activity was assessed over a 5 min recording interval. In this example, two C-fibers with low-grade spontaneous activity were recorded simultaneously. On the left, eachpanel represents the spontaneous activity of one fiber, and each vertical line corresponds to the time of occurrence of an action potential. The action potential waveforms are illustrated on the right. C, Suprathreshold electrical stimulation at the sciatic nerve produced three discrete action potential waveforms at C-fiber latencies. The action potential waveform starting at 21 msec (peak at 22 msec) had the same shape as the spontaneously active fiber 1, providing evidence that the spontaneous activity came from this C-fiber. The two other C-fibers had superimposed waveforms (from 26 to 32 msec). Fiber 2 corresponds to one of these C-fibers.

  • Fig. 2.
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    Fig. 2.

    Histological confirmation of the ventral rhizotomy lesion. A, Spinal roots at the level of the dorsal root ganglion 7 d after ventral rhizotomy, demonstrating a selective lesion of the ventral root axons. The ventral root on theright (asterisk) shows ongoing Wallerian degeneration. The dorsal root ganglion on the left shows intermixed cells and axons of the DRG, with no evidence of injury or fiber degeneration. Magnification, 100×. B, Left lateral plantar nerve 7 d after ventral rhizotomy shows a mixture of degenerating and intact myelinated axons. A myelinated axon undergoing Wallerian degeneration (asterisk) is seen in close proximity to the unmyelinated axons of C-fibers (arrows), a small myelinated axon, and an intact large myelinated axon (on the right). Magnification, 4500×.

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    Fig. 3.

    Ventral rhizotomy produces mechanical hyperalgesia on the side ipsilateral to the lesion and spontaneous activity in C-fibers. A, Mechanical withdrawal thresholds decreased after the lesion but not after the sham surgery. Measurements were made before (open bars) and 7 d after (filled bars) the surgery (*p< 0.05; Wilcoxon matched pairs test). B, Incidence of spontaneous activity in high-threshold C-fibers increases after the L5 ventral rhizotomy (***p < 0.001; χ2test). The proportion of low-threshold fibers with spontaneous activity that responded to gentle brushing of the skin did not change with the lesion. However, the proportion of high-threshold fibers with spontaneous activity that did not respond to gentle brushing of the skin significantly increased after the lesion. C, Hyperalgesia is associated with a high incidence of spontaneous activity. The paw-withdrawal threshold for each animal is plotted as a function of the incidence of spontaneous activity in high-threshold C-fiber afferents for that animal. Animals with low paw-withdrawal thresholds had a higher incidence of spontaneous activity in high-threshold C-fiber afferents. Open symbolscorrespond to sham-operated animals, and filled symbolscorrespond to lesioned animals. D, Distribution of discharge frequencies for the high-threshold, C-fiber afferents. The distribution for the lesioned animals (filled bars) was similar to the distribution for the sham-operated animals (open bars). Data are normalized by the total number of spontaneously active, high-threshold afferents (n = 36, lesioned; n = 13, sham). The experimenters were blinded to the type of surgery at the time of the behavioral and electrophysiological measurements. Seven sham-operated animals and seven lesioned animals were studied.

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    Fig. 4.

    Low-frequency electrocutaneous stimulation at C-fiber strength produces behavioral signs of hyperalgesia. The incidence of paw withdrawal is plotted as a function of time. Electrical stimulation (ES) of the heel (1 pulse every 5 sec for 10 min) was applied at C-fiber strength (filled symbols) or at A-fiber strength (open symbols).A, The response to the 150 mN von Frey probe increased significantly immediately after the termination of the C-fiber stimulation and remained high for 15 min. B, The response to the 75 mN probe also increased significantly after the C-fiber stimulation. There was no significant change in response after the A-fiber stimulation. (* p ≤ 0.05 and **p ≤ 0.01 with respect to average baseline response; ANOVA, followed by paired t test)

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The Journal of Neuroscience: 22 (17)
Journal of Neuroscience
Vol. 22, Issue 17
1 Sep 2002
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Degeneration of Myelinated Efferent Fibers Induces Spontaneous Activity in Uninjured C-Fiber Afferents
Gang Wu, Matthias Ringkamp, Beth B. Murinson, Esther M. Pogatzki, Timothy V. Hartke, Himali M. Weerahandi, James N. Campbell, John W. Griffin, Richard A. Meyer
Journal of Neuroscience 1 September 2002, 22 (17) 7746-7753; DOI: 10.1523/JNEUROSCI.22-17-07746.2002

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Degeneration of Myelinated Efferent Fibers Induces Spontaneous Activity in Uninjured C-Fiber Afferents
Gang Wu, Matthias Ringkamp, Beth B. Murinson, Esther M. Pogatzki, Timothy V. Hartke, Himali M. Weerahandi, James N. Campbell, John W. Griffin, Richard A. Meyer
Journal of Neuroscience 1 September 2002, 22 (17) 7746-7753; DOI: 10.1523/JNEUROSCI.22-17-07746.2002
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Keywords

  • neuropathic pain
  • nerve injury
  • sensitization
  • hyperalgesia
  • neuropathy
  • Wallerian degeneration
  • unmyelinated cutaneous afferent
  • in vivo
  • single nerve fiber recording

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