Abnormal impulse generation in focally demyelinated trigeminal roots

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✓ In 12 cats and two Macaca mulatta monkeys, areas of chronic focal injury were induced in the trigeminal root by implantation of a chromic suture in the nerve near its entry into the brain stem. Experimental lesions were examined histologically and electrophysiologically at 1 week, 3 weeks, and 6 weeks after surgery. At 3 weeks following implantation, lesioned nerves showed areas of focal inflammation surrounding implanted sutures with prominent demyelination of adjacent axons. A total of 497 trigeminal units were studied, 304 of which had associated demyelination of the root. In these 304 cells, two types of abnormal impulse generation from areas of focal demyelination were recorded. Reflected orthodromic action potentials and prolonged high-frequency after-discharges following short priming trains of orthodromic stimuli were observed in 23% and 4% of cells, respectively. Ectopic spike initiation from areas of focal demyelination was not dependent upon anatomical continuity of the nerve with the brain stem, was augmented by hyperventilation, and could be eliminated by the intravenous administration of diphenylhydantoin sodium. The relevance of these findings to the pathophysiological mechanisms of pain syndromes involving peripheral nerves in general and the trigeminal system in particular is discussed.

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Address reprint requests to: Kim J. Burchiel, M.D., Department of Neurological Surgery, University of Washington, Seattle, Washington 98195.

© AANS, except where prohibited by US copyright law.

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Figures

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    A: Recordings from a single cell. Scale: 100 µV and 5 msec; negativity is upward in this and all subsequent figures. Upper Tracing: Response with a doublet to an orthodromic stimulus (o). Lower Tracings: Collision of a second paired stimulus with the extra spike of the doublet shows this spike to be propagating antidromically. B: Paired orthodromic stimuli demonstrate this cell's absolute refractory period of approximately 1 msec. C: Doublet and single action potential response to tactile stimulation of this cell's receptive field.

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    Joint interval histogram of the unit in Fig. 1 shows this cell's responses to an increasing and decreasing frequency ramp of orthodromic stimulation from 10 to 100 Hz, and demonstrates the production of extra spikes (that is, the points of the “arrow pointing to the origin” along the axis representing long followed by short intervals and vice versa). The data are plotted as the duration (msec) of each interspike interval (Ti) versus the next occurring interval (Ti+1).

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    This unit responded with a doublet to a single orthodromic stimulus (arrow) following complete section of the trigeminal nerve at its entry into the brain stem. Scale: 100 µV and 1 msec.

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    Left: A slow sweep of spontaneous activity from a trigeminal unit isolated from a ganglion with an associated root lesion (upper). Firing of this unit was rare during normal ventilation. (Respiratory rate = 10.) Center trace shows a fast sweep of the unit's response to a single orthodromic stimulus (arrow). The underlying poststimulus histogram (lower) sums the unit's response to 250 orthodromic stimuli with respect to time after stimulus occurrence. Right: Fifteen minutes after the respiratory rate was increased threefold, the unit's spontaneous activity is greatly increased, and the unit commonly fires spontaneous doublets (upper). The response to orthodromic stimulus now is two action potentials as shown in the fast sweep (center) and the poststimulus histogram (lower). Vertical scale is 100 µV, upper horizontal scale is 20 msec, lower scale is 1 msec.

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    Left: A unit responded to a single orthodromic stimulus (arrow) with a doublet is shown in the oscillographic tracing (upper) and in the poststimulus histogram (lower), which sum 250 responses. Note that the extra spike does not occur on a one-for-one basis with the expected orthodromic response. Right: One minute after the intravenous administration of 50 mg of diphenylhydantoin the extra spike is abolished.

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    After-discharge of a cell following a brief train of 300 Hz orthodromic stimuli (indicated by bracket). Only the first second of each successive 5-second epoch is shown. Note the 100-msec latency of the after-discharge following cessation of the priming train. Scale: 100 µV and 100 msec.

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    a: Action potentials in an after-discharge evoked by high-frequency stimulation of this cell. b and c: Collision of an orthodromic stimulus (o) with a spike of the after-discharge shows the action potential to be propagating in an antidromic direction toward the periphery. d: Paired orthodromic stimuli demonstrate this cell's absolute refractory period of approximately 0.8 msec. Scale: 100 µV and 2 msec.

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    A: Action potentials within the after-discharge of a unit (1); response of that unit to a single antidromic stimulus (arrow below) (2); collision of the antidromic stimulus with a spike of the after-discharge shows that the after-discharge action potential is travelling in an orthodromic direction toward the brain-stem stimulating electrode (3 and 4). B: Slow sweep of an antidromic stimulus occurring within an after-discharge showing that there is transient blockade of the after-discharge for a brief period following the stimulus. Scale: 100 µV and 2 msec.

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    1 and 3: Low- and medium-power views of a normal trigeminal root section. Luxol fast blue, × 56 (1) and × 300 (3). 2 and 4: Trigeminal root in which two 4–0 chromic sutures were implanted 3 weeks previously. Note the area of demyelination surrounding the implanted sutures. Luxol fast blue, × 56 (2) and × 300 (4). 5: High-power view of a normal trigeminal nerve showing normal axons. Holmes, × 800. 6: Same tissue as is shown in 2 and 4. Note that there are staining axons (arrow) within the demyelinated region adjacent to the suture material. Holmes, × 800.

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