Background
The studies of Sherrington and others showed that in chronic spinalized and decerebrated
preparations reflexes were easily elicitable and responded violently to stimuli, which
otherwise had no effect before injury [[1],[2]]. Hyper-reflexia and spasticity which is velocity dependent increase in muscle tone
[[3]], are considered as signs for corticoreticulospinal system lesions [[4],[5]]. There is also evidence linking the development of spasticity and hyper-reflexia
to changes in spinal α motor neurons excitability [[6],[7],[8]] spinal interneuronal hyperexcitability [[9]] and potentiated synaptic input with muscle stretch [[10],[11],[12],[13],[14]]. However, the exact pathophysiological mechanism which underlies muscle tone and
abnormalities in reflexes is unknown. Although, there is the possibility that peripheral
nerve physiology might be altered after spinal cord injury (SCI), there have been
limited studies to investigate it directly. However, muscle contraction studies showed
significant alteration in muscle properties after SCI [[15],[16]] suggesting that the physiology of the peripheral axons would be altered as a result
of SCI and spasticity.
A recent study by Lin et al., [[17]] demonstrated that the function of the peripheral nerves was altered after SCI in
humans. They specifically found that peripheral nerves were of high threshold and
sometimes were completely inexcitable. They attributed these results to changes in
axonal structure and ion channels. However, there is always the possibility that these
findings might reflect a lower motor neuron lesion in human subjects. Therefore, an
investigation of axonal changes in a more controlled animal model may provide more
unequivocal data.
In the present study, we asked, using an animal model, whether the nerve-muscle complex
(sciatic-triceps surae) becomes hyperexcitable after spinal cord injury. We specifically
hypothesized that excitability measures - amplitude, threshold, latency, conduction
velocity, and stimulus-response curves of nerve and muscle - would demonstrate the
characteristics of hyperexcitability in nerve-muscle complex after SCI. Moreover,
we hypothesized that muscle twitches will demonstrate the properties of spastic muscle
as reported by Harris et al., [[15]]. The present investigation gives evidence that sciatic-triceps surae complex is
indeed hyperexcitable after SCI. Thus, it may provide an additional mechanism for
spastic syndrome that develops after SCI.
Methods
Animals
Experiments were carried out on CD-1 male and female adult mice in accordance with
NIH guidelines, with all protocols approved by the College of Staten Island IACUC.
Animals were housed under a 12 h light-dark cycle with free access to food and water.
Spinal cord contusion injury
Mice were deeply anaesthetized with ketamine/xylazine (90/10 mg/kg i.p.). A spinal
contusion lesion was produced (n = 7) at spinal segment T13 using the MASCIS/NYU impactor
[[18]]. The impactor was fitted with a 1 mm-diameter impact head rod (5.6 g) released
from a distance of 6.25 mm onto T13 spinal cord level exposed by a T10 laminectomy.
After the injury, the overlying muscle and skin was sutured, and the animals were
allowed to recover under a heating lamp at 30°C. To prevent infection after the wound
was sutured, a layer of ointment containing gentamicin sulfate was applied. Following
surgery, animals were maintained under pre-operative conditions for ~8 months before
testing. The time of recovery was selected to ensure a stable chronic SCI during testing.
Behavioral testing
The following behavioral evaluation were performed just before the electrophysiological
studies, approximately 8 months after SCI.
Basso mouse scale (BMS)
Motor ability of the hindlimbs was assessed by the categorical motor rating of BMS
[[19]], using rating system of: 0, no ankle movement; 1-2, slight or extensive ankle movement;
3, plantar placing or dorsal stepping; 4, occasional plantar stepping; 5, frequent
or consistent plantar stepping; no animal scored more than 5. Each mouse was observed
for 4 min in an open space before a score was given.
Abnormal posture scale (APS)
After SCI, animals usually developed muscle tone abnormalities that were exaggerated
during locomotion. We developed a posture scale to quantify the number of muscle tone
abnormalities demonstrated by the animals. The rating scale ranges from 0 to 12 with
a cumulative score based on the sum of the following abnormalities: limb crossing
of midline, abduction, and extension or flexion of the hip joint, paws curling or
fanning, knee flexion or extension, ankle dorsi or planter flexion. A score of one
was given for each abnormality. The total score is the sum of abnormalities from both
hindlimbs. Abnormal postures were usually accompanied by spasmodic movements of the
hindlimbs.
Electrophysiological procedures
Intact (n = 7) and SCI (n = 7) animals underwent a terminal electrophysiological experiment.
Animals were anesthetized using ketamine/xylazine (90/10 mg/kg i.p). Electrophysiological
procedures started approximately 45 min after the first injection to maintain anesthesia
at moderate to light level [[20]]. As needed, anesthesia was kept at this baseline level using supplemental dosages
(~5% of the original dose).
The skin covering the two hindlimbs was removed. Both triceps surae muscles were partially
separated from the surrounding tissue preserving blood supply and nerves. The tendon
of each of the muscles was connected to the force transducers with a hook shaped 0-3
surgical silk thread. In addition, the sciatic nerve was cleared from the surrounding
tissue from the knee to the hip joint. The tissue was kept moist by drops of saline.
Both hind and fore limbs and the proximal end of the tail were rigidly fixed to the
base. Muscles were attached to force displacement transducers (FT10, Grass Technologies,
RI, USA); the muscle length was adjusted to obtain the strongest twitch force (optimal
length). The whole setup was placed on an anti-vibration table (WPI, Sarasota, FL,
USA). Animals were kept warm during the experiment with radiant heat (27°C).
A stainless steel bipolar stimulating electrode (500 μm shaft diameter; 100 μm tip;
FHC, ME, USA) was set on the exposed sciatic nerve close to the hip joint (2 cm from
the recording electrode) ([Figure 1A]). Electrode was then connected to stimulator outputs (PowerLab, ADInstruments, Inc,
CO, USA). Extracellular recordings were made with pure iridium microelectrode (0.180
mm shaft diameter; 1-2 μm tip; 5.0 MΩ; WPI, Sarasota, FL, USA). The recording electrodes
were inserted into the sciatic nerve branch that innervates the triceps surae muscle
([Figure 1A]). The proper location was confirmed by penetration-elicited motor nerve spikes,
which were correlated with muscle twitches ([Figure 1B]). Recording electrode site was ~3 mm from the muscle. It is important to emphasize
that the location of the recording and stimulating electrodes was maintained consistent
across all animals. The record of extracellular activity was passed through a standard
head stage, amplified, (Neuro Amp EX, ADInstruments, Inc, CO, USA) filtered (bandpass,
100 Hz to 5 KHz), digitized at 4 KHz, and stored in the computer for subsequent processing.
A power lab data acquisition system and LabChart 7 software (ADInstruments, Inc, CO,
USA) were used to acquire and analyze the data.
Figure 1 Sciatic nerve recording. A: anatomical illustration of sciatic nerve branches seen under the microscope.
The tibial nerve (black) has three branches supplying the triceps surae muscle. The
recording electrode (R) is inserted into the tibial nerve just before it enters the
muscle. The stimulating electrode is situated 2 cm away from the recording electrode.
B: Spontaneous activity from the tibial nerve that was correlated with muscle twitches
confirming that the location of the recording (R) electrode is in the nerve bundle
that innervates the triceps surae muscle. S - bipolar, stimulating electrode
Stimulus-muscle and stimulus-nerve response curves were generated by delivering stimuli
(1 ms duration), which were increased in steps (in Volts) starting from 0.05, and
then increasing from 0.1, to 1.0, and from 2 to 10, in 0.1 V and 1 V increments, respectively.
To determine the strength-duration time constant (SDTC), a test protocol was used
with 17 stimuli of different durations (10, 20, 30, 40, 50, 70, 90, 150, 200, 300,
400, 600, 800, 1000, 2000 μs). The strength of the stimulation (mA) was adjusted accordingly
for each of the durations tested to elicit minimal (all or none) triceps surae muscle
response (contraction). In the same group of animals, a test stimulus of two durations
(10 and 1000 μs) was used to measure the time constant of 40% of maximal muscle contraction.
The threshold charge (threshold current × stimulus duration) was plotted against the
stimulus duration. The time constant is given as the negative intercept of the linear
regression line of the threshold charge against stimulus duration on the duration
axis.
Data analysis
F-wave was elicited by application of the stimulus equal in strength to superamaximal
stimulation necessary to generate M-wave. F-wave latency was measured from stimulus
artifact to the early onset of F-wave and was determined as the average of at least
10 F-waves from each animal. The peripheral motor conduction time (PMCT) was calculated
by:
Where M is the latency of the M-response, F is the latency of the F-wave. The 1 ms term is a correction for the delay in re-excitation
of the motoneuron [[21]].
We recorded the time from the start of the stimulus artifact to the onset of the first
deflection of nerve compound action potential (nCAP) as well as muscle twitch. Latency
of muscle twitch was also measured as the time from the earliest onset of nCAP to
the earliest onset of muscle twitch. Measurements were recorded using a cursor and
a time meter on LabChart software. The amplitude of sciatic nerve nCAP was measured
as peak-to-peak. Analysis of muscle contractions were performed with peak analysis
software (ADInstruments, Inc, CO, USA), as the height of twitch force measured relative
to the baseline. Slopes for muscle contractions were extracted through Matlab-based
calculations (MathWorks, Natick, MA).
Statistical analysis
All data are reported as group means ± SEM. One sample t-tests were used for single
group. Two sample student’s t -tests (or Mann-Whitney Rank Sum Test) was used for two groups; statistical significance
at the 95% confidence level. To compare multiple measurements, we performed one way
ANOVA with Solm-Sidak corrections for post hoc analysis. Statistical analyses were performed using SigmaPlot (SPSS, Chicago, IL),
Excel (Microsoft, Redwood, CA), and LabChart software (ADInstruments, Inc, CO, USA).
Results
We used BMS and APS to identify the animals with SCI those developed locomotor and
muscle tone abnormalities. BMS showed that animals with SCI had significant locomotor
abnormalities (22.22% ± 4.9% of control). In addition, APS showed that animals with
SCI had significant increase in the number of muscle tone abnormalities (9.1 ± 0.59).
To establish the excitability of the nerve-muscle complex in animals with SCI, we
compared the stimulus-response (twitch force) curve generated from animals with SCI
to that generated from the controls. Stimulus-response curve of SCI animals was shifted
to the left at stimuli level(s) of less than 2 V ([Figure 2A]). This clearly suggests that nerve-muscle complex in SCI animals is of lower threshold
compared to controls. The difference between SCI animals and controls was most obvious
at stimulus intensities between 0.7 to 1 V (p < 0.05, [Figure 2A] &[2B]). In SCI animals, when stimulus-response curves from strong and weak muscles were
compared, obvious differences emerge between the two curves (see [Figure 2C]). Although weak muscles had weak responses, they had very low thresholds. In SCI
animals, responses from strong muscles had intermediate thresholds. The minimal threshold
defined as the least stimulus intensity at which muscles would respond was also calculated.
In [Figure 2D], the average minimal threshold (averaged for strong and weak muscles) in SCI animals
(0.71 ± 0.06 V) was significantly less than in the controls (1.19 ± 0.14 V) (p < 0.01).
These results suggest that muscle contraction is more easily evocable in SCI animals,
as compared to controls.
Figure 2 Muscle twitches, evoked by sciatic nerve stimulation, in control and spinal
cord injured (SCI) animals. Stimulus-response curves were generated by stimulating the sciatic nerve and recording
muscle twitches from the triceps surae muscles. A: Representative twitches from animals
with SCI (red) and control (black) obtained by stimulus with intensity of 0.7 mA.
B: Cumulative averages of the muscle responses from SCI and control animals plotted
against stimulus intensity. It is noteworthy that muscle twitches are more easily
evocable in animals with SCI than in controls. Note also the difference became differentiated
at stimulus intensities 0.7 to 1 V (p < 0.05). C: In SCI animals, stimulus-response
curve in weak muscles was different from that in strong muscles. Note that the threshold
in weak muscles (0.05 V) was much lower than the threshold in strong muscles (0.6
V). D: Average minimal threshold was significantly lower in SCI animals compared to
controls (p < 0.003).
Since muscle contraction involves many steps before its occurrence (including nerve
excitation, neuromuscular transmission and muscle membrane excitation), it should
be considered an indirect measure for nerve excitability. Therefore, to estimate the
nerve excitability, we recorded nCAP from the tibial branch of the sciatic nerve that
supplies the triceps surae muscle. [Figure 3A] shows an increase in the amplitude of nCAP as well as shorter latency in nCAP recorded
from SCI animals compared to controls. In [Figure 3B], stimulus-response curves from SCI animals and controls show that sciatic nerve
in SCI animals is of low threshold
Figure 3 Sciatic nerve compound action potentials (nCAP) from injured and control
animals (averages for both limbs). A: an overlay of two nCAPs from animal with SCI (red) and control (black). Note
that nCAP from SCI has shorter latency than control. Filled triangle indicates stimulus
artifact. B: stimulus-response curves show that sciatic nerves responses were of low
threshold and larger amplitude in SCI animals (open circles), compared to controls
(filled circles). The non-linear relationship between stimulus intensity and nCAP
is represented by polynomial curve fit. Note that the fit for SCI (–-) is shifted to the left compared to controls (–) suggesting an increase in excitability.
C: response:stimulus ratio was calculated for all submaximal nCAP (*p < 0.05). D:
nCAP latency measured from the onset of stimulus artifact to
To further illuminate this finding, the response to stimulus ratio for all submaximal
nCAP was calculated and was found ([Figure 3D]) to be significantly higher in SCI animals (1436.3 ± 531.2%) than in controls (206.3
± 29.7%) (p < 0.05). nCAP latency in SCI was significantly shorter (2.4 ± 0.2 ms)
than in controls (3.0 ± 0.2 ms) (p < 0.01, [Figure 3D]).
SDTC was significantly higher in SCI animals (0.3 ± 0.009 ms) than in controls (0.09
± 0.003 ms) (p < 0.02) for all or none responses ([Figure 4A]). SDTC was also significantly higher in SCI animals (0.1 ± 0.02 ms) than controls
(0.005 ± 0.001 ms) for muscle contraction equal to 40% of maximal muscle response
(p < 0.01; [Figure 4B]). These results suggest demyelination and/or increase in persistent Na+ currents.
Figure 4 Strength-duration time constant (SDTC) for the sciatic nerve. A: SDTC for sciatic nerve of minimal threshold (defined as the current strength
at which an all or non-response of triceps surae muscle is elicited) of control (black
bar) and SCI (gray bar) animals are shown. B: SDTC was measured for the same groups
of animals in A for triceps surae muscles responses of 40% of maximum (mean ± SE);
stimulus durations of 0.01 ms and 1 ms were used.
The latency of muscle contraction measured from the stimulus artifact to the onset
of muscle contraction ([Figure 5A]), was significantly shorter in SCI animals (6.9 ± 0.3 ms) as compared to the controls
(7.9 ± 0.4 ms) (p < 0.02) ([Figure 5B]). Latencies between the onset of nCAP and the onset of muscle contraction was significantly
shorter in SCI animals (4.2 ± 0.3 ms) than in the controls (5.1 ± 0.3 ms) (p < 0.05)
([Figure 5C]). Similar to axons, these results indicate that muscle responses of the SCI group
were rapid as well. This may be indicative of changes in either neuromuscular transmission
or excitation-contraction coupling.
Figure 5 The latency of muscle contractions. A: an overlay of muscle twitches from control (black) and SCI animals (red). The
boxed area is enlarged in the inset on the right to show the difference in the onset
of muscle contraction. The filled triangle marks the time of the stimulus. B: muscle
contraction latency, measured from the onset of the stimulus artifact, was significantly
shorter in SCI animals compared to control (*p < 0.022). C: muscle contraction latency,
measured from the onset of nCAP, was also significantly shorter in SCI animals compared
to controls (*p < 0.034).
F-waves analyses were performed to evaluate changes along the peripheral motor nerve
after SCI. [Figure 6A] illustrates some of the differences in F-waves between SCI and control animals.
Although there was a visible reduction in the amplitude of F-wave in SCI animals,
it was not statistically significant ([Figure 6B]). However, the latency of F-wave was significantly reduced in SCI animals (0.011
± 0.001 sec) when compared to controls (0.021 ± 0.002 sec) (p < 0.001, [Figure 6C]). PMCT was also significantly reduced (-0.493 ± 0.001 sec) when compared to controls
(-0.488 ± 0.001 sec) (p < 0.01, [Figure 6D]). Additional analysis established no significant correlation between PMCT values
and measured parameters (age, body length and weight) in either SCI or control animals.
Therefore we concluded that the PMCT is a good estimate for changes in conduction
velocity.
Figure 6 Changes in F-wave and peripheral motor conduction time (PMCT) after spinal
cord injury (SCI). A: superimposed traces show F-waves from control and SCI animals. Motor responses
were clipped for clarity. B: there was a trend of reduction in F-wave amplitude in
SCI animals however, did not reach statistical significant compared to controls (p
> 0.05). C: F-wave latency was significantly shorter in SCI animals than in controls
(*p < 0.001). D: PMCT was significantly lower in SCI animals compared to controls
(*p = 0.001).
The twitch properties were analyzed to gain better understanding of the many simultaneous
changes occurring in the peripheral nerves and muscles after SCI. These twitches were
measured at the maximal twitch force of each muscle, using the data shown in [Figure 1]. [Figure 7A] depicts the representative twitches normalized to twitch peak force. The twitches
from SCI animals appear slower in rising and falling (lower slopes) compared to the
twitches from the controls. The rising and falling slopes were highly correlated (Pearson
Correlation, r = 0.96, p < 0.01, [Figure 7B]), which indicates coupling between the processes responsible for the two events.
The mean rising slope was significantly lower in SCI animals (0.13 ± 0.02) compared
to those of the controls (0.25 ± 0.05) (p < 0.05, [Figure 7C]). The mean overall falling slope was significantly lower in SCI animals (-0.11 ±
0.03) when compared to controls (-0.03 ± 0.01) (p < 0.02, [Figure 7D]). The decay function of muscle twitch was divided into two periods, marked (b) and
(c) in [Figure 7A]. Falling slopes of these two periods were calculated separately, assuming that they
represent different motor units. The mean falling slope of the first period (b) in
SCI animals (-0.13 ± 0.03) was not statistically significant from controls (-0.19
± 0.06) ([Figure 7E]). In contrast, the mean falling slope of the second period (c) in SCI animals (-0.02
± 0.002) was significantly lower than the controls (-0.05 ± 0.01) (p < 0.02, [Figure 7F]).
Figure 7 Changes in muscle contraction properties after SCI. A: representative normalized muscle twitches from SCI (red) and control (black)
animals normalized to peak twitch force. Note the slow rising and falling of the twitch
from SCI animals. The curve segments marked a, b, and c are different periods of muscle
contraction that was analyzed separately below (the straight line marks the (b) segment
of the curve). B: A significant correlation between rising and falling slopes, indicating
that twitches with higher rising slope are associated with higher falling slope value.
Data in B are from all muscles of SCI and control animals. C: The mean value of the
rising slope in normal animals was significantly higher than in controls (*p = 0.033).
D: The mean value of the falling slope of the entire decay period (b and c) was significantly
lower in SCI animals compared to control. E: The mean value of the first part of the
decay period of muscle contraction marked (b) was lower on SCI compared to control,
however, the difference was not statistically significant (p = 0.411). F: The mean
value of the falling slope at the last part of the decay marked (c), was significantly
lower in SCI animals compared to controls (p = 0.012).
Discussion
The results show that the spinal cord injury leads to increased excitability of nerve-muscle
complex. Several measures of excitability were employed in the present study. An increase
in nerve conduction velocity was accompanied by reduced threshold for nCAP generation
and an increase in its amplitude. Thus, the muscle could be excited easier and faster.
Moreover, reduction in the duration of PMCT indicates that post-injury axonal changes
lead to an increase in the conduction velocity along the whole motor nerve from the
spinal cord to the site of the recording electrode located very close to the muscle.
These results confirm the finding in paralyzed rats by Cope et al [[22]], however these results contradict the finding in human with SCI [[23]].
Importantly, SDTC was significantly increased in the sciatic nerves of injured animals.
This suggests demyelination and/or increased persistent sodium current [[24]]. The analysis of properties of muscle twitch in SCI animals revealed slowness in
the rate of muscle contraction and relaxation. Similar changes were reported by Harris
and collaborators [[15]] investigating segmental tail muscle in the rats. Since our experiments were performed
on triceps surae muscle in mice, one can conclude that spinal cord injury might cause
similar changes in all spastic muscles and across species.
In the present study, all injured animals exhibited behavioral signs of spasticity
and demonstrated spasms. This indicates that the SCI that leads to spasticity may
also be responsible for the increase in excitability of axons and muscles. It is known
that spinal cord injury or brain damage results in hyperexcitability of neuromuscular
system (expressed as dystonia, spasticity, spasm and hyper-reflexia). Although possible
mechanisms of hyperexcitability may include among others the increased excitability
of spinal motoneurons [[6],[7],[8]], spinal interneuronal hyperexcitability and potentiated synaptic input to the muscle
[[10],[11],[12],[13],[14]] the exact mechanism of this phenomenon remains largely unknown. Our results expand
current views on the hyperexcitability-mediating mechanisms, demonstrating that the
whole neuromuscular complex becomes hyperexcitable and may participate in the mechanisms
of spastic syndrome and its expression. This notion contradicts recent findings described
by Lin et al., [[17]], who reported higher axonal threshold in human subjects with SCI. These differences
may be due to a complex pathophysiology of SCI in humans which may be additionally
complicated by nerve root injury. While pathophysiology of SCI in humans has been
subdivided into several different types [[25]]which can involve both peripheral and central damage, experimental damage of the
spinal cord in animals represents reproducible injury executed in a well controlled
fashion. The lesions are usually localized and limited to the zone of approximately
700 μ without apparent root damage (Ahmed, unpublished observation). The effects of
SCI can also depend on the type of the muscle innervated by a damaged spinal cord
segment. While Lin et al., [[17]] evaluated motor pathway of tibialis anterior, triceps surae muscle and its innervations
was the subject of our research. In support of this notion Yoshimura and Groat [[26]] reported that in SCI rats there was an increase in the excitability of the afferent
neurons innervating urinary bladder but there was no change in neurons innervating
the colon.
Inferences from the present results point to lesion-induced intrinsic changes in the
peripheral axons and muscles. SDTC reflects mostly passive properties of the membrane
at the nodes of Ranvier [[27]]. Its increase in SCI animals might indicate injury-induced demyelination and/or
an increase of the expression of sodium channels (particularly persistent Na+ channel) at the nodes, similarly as reported by Yoshimura and Groat [[26]] in afferents to urinary bladder, and observed by us in the sciatic nerve (unpublished
observation). While upregulation of the sodium channel expression, or an increase
in their rate activation constant [[28]] could reflect additional processes responsible for the increased conduction velocity,
it can also be influenced by changes in axon diameter, myelin capacitance, and axoplasmic
conductance [[29],[30]]. An increase in any of these factors with the exception of myelin capacitance would
increase the conduction velocity. An increase in the diameter of the spinal neurons
(which enhances axoplasmic conductance) observed after SCI [[31],[26]] could also take place in our animals and be responsible for observed increase in
conduction velocity. In addition to axonal diameter, the axoplasmic conductance (and
subsequently conduction velocity) can be enhanced by limited hypomyelination of the
axon especially at the internode regions [[32]]. The hypomyelination could also induce up-regulated expression of the sodium channels
and ensuing hyperexcitability, as reported for shiverer mouse brain [[33]].
A model of the possible sequence of events that may lead to changes in axonal excitability
is illustrated in [Figure 8]. The intense barrage of activity that occurs at the onset of the lesion is an event
that might change the ionic composition of extra- and intra-cellular environments.
As reported by us previously, the axonal excitability is regulated by its previous
activity [[16]], and electrical stimulation of sciatic nerve causes the nerve to release preloaded
glutamate analog [[34]]. Thus, axonal neurotransmitter release and ionic composition changes after intense
activity at the onset of spinal cord lesion may play a role in the consequent axonal
excitability changes. Alternatively, spinal shock that can persist up to several weeks
after SCI [[35]], may also lead to hypomyelination followed by hyperexcitability of peripheral axons.
Figure 8 The model of events which may lead to hyperexcitability and atrophy after
SCI. Each event may represent a potential target for clinical intervention. Two pathways
are posited for hypomyelination: SCI causes immediate intense activity that may initiate
mechanisms that eventually lead to hypomyelination, or the period of inactivity that
followed spinal cord injury called spinal shock. Either way hypomyelination (in lesion
environment) would lead to upregulation of sodium channels (Na+ II) that will cause hyperexcitability. According to Waxman hypothesis [[38]] the activity of these channels would lead to reversed action of Na+- Ca2+ exchanger, followed by an increase in intracellular Ca2+concentration, axonal death and subsequent muscle atrophy.
There was difference in threshold between week and strong muscles in animals with
SCI. In that, weaker muscles expressed lower threshold than stronger muscles, becoming
hyperexcitable. However, it has been reported that the weakness of the muscle induced
by disuse in intact animals does not lead to hyperexcitability [[36],[37]]. This implies that hyperexcitability is not induced by injury-related disuse of
the weak and spastic muscles, but might result from interaction between the effects
of disuse and lesion-induced processes.
In conclusion, we have demonstrated that the nerve-muscle complex becomes hyperexcitable
in animals with SCI. The nCAP from the sciatic nerve was of higher amplitude, lower
threshold, longer strength-duration time constant, and faster conduction velocity.
In addition, the earliest onset of muscle contraction from the triceps surae muscle
was shorter in SCI animals when compared to controls. Muscle twitches were of slower
rising and falling slopes, with prolonged contraction duration in SCI animals compared
to controls. These findings show that after SCI motor axons undergo excitability changes
similar to their perikarya in the ventral horn of the spinal cord [[6],[7],[8]]. One might speculate that hyperexcitability of peripheral motor axons after SCI
injury may partially underlie the expression of spastic syndrome seen after SCI.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
ZA design, analyze and perform the experiments and wrote the paper. RF assisted in
data analysis and revising the manuscript. AW assisted in interpreting the data and
in writing and revising the manuscript. All authors read and approve the final manuscript.
Cite this article as: Ahmed et al., Excitability changes in the sciatic nerve and triceps surae muscle after spinal cord
injury in mice Journal of Brachial Plexus and Peripheral Nerve Injury 2010, 5:8
