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Published in final edited form as:
Exp Brain Res. 2006 January ; 168(4): 577–586.

Modulation of flexion reflex induced by hip angle changes inhuman spinal cord injury
Maria Knikou, Elizabeth Kay, and William Zev Rymer
Sensory Motor Performance Program, Rehabilitation Institute of Chicago, Chicago, IL, USA
The Feinberg School of Medicine, Department of Physical Medicine and Rehabilitation,
Northwestern University, Chicago, IL, USA
Biology Department, Programs in Physical Therapy, Neuroscience Graduate School, College ofStaten Island, City University of New York, 2800 Victory Boulevard, Bldg 5N-207, Staten Island, NY
10314, USA

Abstract
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The flexion reflex can be elicited via stimulation of skin, muscle, and high-threshold afferents
inducing a generalized flexion of the limb. In spinalized animal models this reflex is quite prominentand is strongly modulated by actions of hip proprioceptors. However, analogous actions on the flexion
reflex in spinal cord injured (SCI) humans have not yet been examined. In this study, we investigatedthe effects of imposed static hip angle changes on the flexion reflex in ten motor incomplete SCI
subjects when input from plantar cutaneous mechanoreceptors was also present. Flexion reflexes
were elicited by low-intensity stimulation of the sural nerve at the lateral malleolus, and were recorded
from the ipsilateral tibialis anterior (TA) muscle. Plantar skin stimulation was delivered through two
surface electrodes placed on the metatarsals, and was initiated at different delays ranging from 3 to
90 ms. We found that non-noxious sural nerve stimulation induced two types of flexion reflexes in
the TA muscle, an early, and a late response. The first was observed only in three subjects and evenin these subjects, it appeared irregularly. In contrast, the second (late) flexion reflex was present
uniformly in all ten subjects and was significantly modulated during hip angle changes. Flexion
reflexes recorded with hip positioned at different angles were compared to the associated control
reflexes recorded with hip flexed at 10°. Hip flexion (30°, 40°) depressed the late flexion reflex,
while no significant effects were observed with the hip set in neutral angle (0°). Strong facilitatory
effects on the late flexion reflex were observed with the hip extended to 10°. Moreover, the effectsof plantar skin stimulation on the flexion reflex were also found to depend on the hip angle. The
results suggest that hip proprioceptors and plantar cutaneous mechanoreceptors strongly modulate
flexion reflex pathways in chronic human SCI, verifying that this type of sensory afferent feedback
interact with spinal interneuronal circuits that have been considered as forerunners of stepping andlocomotion. The sensory consequences of this afferent input should be considered in rehabilitation
programs aimed to restore movement and sensorimotor function in these patients.

Keywords
Cutaneous afferents; Flexion reflex; Hip proprioceptors; Rehabilitation; Sensorimotor integration

E-mail:knikou@mail.csi.cuny.edu, Tel.: +1-718-9823316, Fax: +1-718-9822984.

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Flexion reflexes are polysynaptic responses securing withdrawal of skin areas from a potential
offending stimulus (Sherrington 1910). However, beyond this nociceptive function, flexion
reflexes appear also to be tightly coupled with posture and locomotion (Lundberg 1979,
Grillner 1981). Because of the consistent actions of many different afferents involved in thegeneration of the flexion reflex (e.g., excitation of flexors and inhibition of extensors), thesewere termed as flexion reflex afferents (FRA) (see reviews of Lundberg 1979; Hultborn andIllert 1991), although diverse actions not belonging to the classical FRA model have also beenreported (Schomburg 1990), verifying that these FRA responses, which ‘may’ evoke flexion
reflexes, have access to other mutually exclusive alternative pathways, as originally proposedby Eccles and Lundberg (1959).

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Excitation of FRA induces two different classes of flexion reflexes, for example, an early anda late reflex. The early flexion reflex in individuals with a spinal cord injury (SCI) resembles
the early flexion reflex observed in neurologically intact subjects and in spinal cats (Meinck
et al. 1985; Anden et al. 1966a). In the acute spinal cat, FRA excitation at a non-nociceptive
level generates a widespread short latency excitation of many flexor motor pools (Anden et al.
1966a). However, activation of spinal monoaminergic terminals by intravenous injection of ldopa depresses transmission in the short-latency flexion reflex and releases long-latency FRA
pathways resulting in a long lasting excitation of flexor motor pools with concomitant extensor
inhibition (Anden et al. 1966b, c). Because of the strong reciprocal expression of this response
between excitatory interneuronal pathways (from ipsi- and contralateral FRA) to flexor andextensor motoneurons, Jankowska et al. (1967a, b) suggested that this reflex is also involvedin spinal stepping, verified by the alternating bursts of flexor and extensor activity following
administration of Nialamide (Jankowska et al. 1967a). Excitation of FRAs at a non-nociceptive
level induces also a late flexion reflex in individuals with a motor complete SCI (Roby-Brami
and Bussel 1987; Knikou and Conway 2005), which displays similar characteristics to thatobserved in the spinal cat after l-dopa (Roby-Brami and Bussel 1990, 1992).

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Several studies have concentrated also on the nociceptive flexion withdrawal reflex, which
combines flight and defence movements (Sherrington 1910). In healthy humans, this reflex
has a short central conduction time and is thus related to early flexion reflexes (Hagbarth andFiner 1963). Following a SCI, the nociceptive early flexion reflex is still observable in thebiceps femoris muscle (Dimitrijevic and Nathan 1968). It is apparent that nociception or
cutaneous sensation determines the type of the flexion reflex elicited, and it should be
mentioned that the nociceptive flexion reflex is not synonym to the late flexion reflex evokedby non-noxious stimulus, which presents the ‘‘flexion phase of the alternating reflex act of
stepping,’’ as originally proposed by Sherrington (1910).
Previous work has shown that the flexion reflex is influenced by limb posture, site ofstimulation, electrically-induced muscle contraction, and by actions of descending pathways(Hagbarth 1952; Andersen et al. 1999; Baxendale and Ferrell 1981; Schomburg 1990;
Baldissera et al. 1981; Knikou and Conway 2005). In the acute spinal cat preparation, lateflexion reflexes are generated by spinal interneurons that are strongly modulated by signals
transmitting hip position (Grillner and Rossignol 1978). Similar findings have also beenreported in spinal-injured man (Conway and Best 1995). Hip proprioceptors modulate
substantially soleus H-reflex excitability, actions of spinal inhibitory interneurons exerted
either from group Ia or Ib afferents, and interact with plantar cutaneous mechanoreceptors toalter soleus H-reflex magnitude in both SCI and able-bodied subjects (Knikou and Rymer
2002a, b; Knikou 2005 Knikou 2006). These actions signify that hip proprioceptors participate
in complex interneuronal circuits that have been linked to human posture and locomotion (seereview of Baldissera et al. 1981). Recent studies have demonstrated that hip-mediated afferent

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input modulates locomotion in human SCI by enhancing the swing phase following apronounced hip extension (Dietz et al. 1998, 2002). Similar results were also reported in infants
during walking, where hip proprioceptors interacted with load pathways leading to an enhanced
swing driven by exaggerated hip extension (Pang and Yang 2000).
In the cat, activation of mechanoreceptor afferents of the foot sole delay the initiation of swing,
inhibit late flexion reflexes, and promote stance (Duysens and Pearson 1976; Duysens 1977;
Conway et al. 1995), signifying the functional interaction of the plantar mechanoreceptors withflexion reflex pathways. Recent studies support the notion that cutaneous afferents shape thelocomotor pattern and contribute to the recovery of stepping following spinalization in the cat(Bouyer and Rossignol 2003). In humans, proprioceptive information from the foot solecontributes to the maintenance of erect posture (Kavounoudias et al. 2001), probably bystrengthening the ongoing motoneuronal discharge (Kernell and Hultborn 1990).

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Collectively, there is considerable evidence that activation of plantar cutaneous afferents or
hip proprioceptors can independently influence flexion reflex excitability. The present study
was undertaken to investigate the contribution of hip proprioceptors and plantar cutaneousafferents on flexion reflex excitability in ten motor incomplete SCI subjects under precisely
controlled experimental conditions. We found that the late flexion reflex was either inhibitedor facilitated depending on the imposed hip angle of the ipsilateral leg. We also found that
excitation of plantar cutaneous mechanoreceptor afferents during hip angle changes either
facilitated or depressed the flexion reflex depending on the hip angle. These findings strongly
support the notion that hip-mediated afferent input interacts with complex spinal interneuronal
circuits associated with control of walking in humans. Preliminary accounts of this work havebeen presented in abstract form (Knikou et al. 2005).

Materials and methods
Subjects
All experiments were approved by the Institutional Review Board (IRB) of the Northwestern
University (Chicago, IL, USA), and conducted according to the 1964 Declaration of Helsinki.
Informed consent was obtained from all subjects or from their parents prior to testing. Ten
subjects with SCI ranging from C5–8 and T3–11 participated in the study. Subjects
participating in the current tests are the same who participated in a previous study (Knikou
2005), and are identified with the same numbers.

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The impairment scale of the American Spinal Injury Association (ASIA) (Maynard et al.
1997) was employed to classify the completeness of the lesion. Joint and muscle proprioception
was assessed by asking the subjects to identify the position and direction of movement in the
joints of both lower extremities with eyes closed, performed passively by the experimenter.
For cutaneous sensation assessment, subjects were asked to identify with eyes closed, the sitewhere a piece of cotton and/or needle touched them. None of the subjects had signs of lower
motoneuron disorder. Subjects’ characteristics are summarized in Table 1.
Subject position
Each subject was transferred to the adjustable chair of a Biodex Rehabilitation/Testing System
2 (Biodex Medical Systems, Shirley, NY, USA), and was positioned supine. The right lower
limb was secured to a knee ankle foot orthosis (KAFO), previously used in similar studies in
SCI subjects (Knikou and Rymer 2002b; Knikou 2005). For each subject, adjustments weremade to fit shank and thigh lengths, with ankle and knee joints set at 20° of plantar flexion and
30° of flexion, respectively. The KAFO was connected to the motor head of the Biodex. With
the KAFO secured to the lower limb, the center of the subjects’ hip joint was aligned with the

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center of the Biodex motor head unit. The leg was moved in the sagittal plane by theexperimenter. During the experiment, the head and arms were fully supported and subjects
were asked to relax.
TA flexion reflex (elicitation and recording protocol)
The flexion reflex was evoked by electrical stimulation of the sural nerve, according to theprocedures described by Roby-Brami and Bussel (1987). The sural nerve was stimulated at theright lateral submalleolar region through two disposable pre-gelled Ag-AgCl electrodes (AmbuInc., Denmark). The rationale for choosing the sural nerve was that it is a pure sensory nerve,in contrast to the posterior tibial nerve which is a mixed nerve innervating both skin and muscle.
The reflex was evoked by a 30 ms pulse train of 1–ms pulses delivered at 300 Hz once every
10 s, generated by a constant current stimulator (DS7A, Digitimer, UK). At this interstimulusinterval, no evidence of habituation in the flexion reflex was encountered (Fuhrer 1976).
Surface electromyograms (EMG) were recorded by a single differential electrode (DE-2.1;
DelSys, Boston, MA) placed over the ipsilateral TA muscle following light mechanicalabrasion of the skin. The recorded EMG signals were amplified and band-pass filtered (10 Hz–
1 kHz) before being sampled at 5 kHz (LabView PCI-MIO-16E-4, Texas National Instruments
Inc., USA).

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At the beginning of each test, the stimulus delivered to the sural nerve was set at 0 mA andwas increased slowly so to observe the evoked response on the digital oscilloscope screen. The
stimulus intensity during which the initial EMG TA activity was induced was identified as thereflex threshold (RT). This reflex response was categorized as early if its latency was less than
100 s, and as late when its latency was beyond 120 ms (Roby-Brami and Bussel 1987). Further
increments in stimulus strengths were delivered so to observe if the expression of the flexion
reflex changed with increments in the stimulation intensity. During testing, the sural nerve wasstimulated at 1.5×RT. At this intensity, no limb movement was evoked and subjects reported
no pain following sural nerve stimulation, indicating that the test afferent volley included large
muscle and cutaneous afferents eliciting the non-nociceptive flexion reflex (Sherrington
1910).
Conditioning stimulation (electrical): excitation of plantar cutaneous afferents

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The experimental protocol employed to excite plantar cutaneous afferents was identical to that
previously employed to condition the soleus H-reflex with hip set at different angles in thesame SCI subjects (Knikou 2005). Two Ag-AgCl surface electrodes (Ambu Inc., Ølstykke,
Denmark) were placed transversely across the first and third metatarsals. Using a constantcurrent stimulator (DS7, Digitimer, UK), the perceptual threshold (PT) that corresponded tothe stimulus intensity first perceived by the subject was established. All conditioning stimuli
were equivalent to 3×PT. At this stimulation intensity no movement of the intrinsic musclesof the foot was elicited and no pain was reported, signifying that the conditioning afferent
volley excited mainly low-threshold plantar cutaneous afferents. Tactile units remain largely
intact after chronic SCI (Thomas and Westling 1995), thus transmission of plantar skinsensation was not regarded as problematic in the current study.
The conditioning stimulus train consisted of five pulses with an inter-stimulus interval of 4.8
ms and pulse train duration of 24 ms. The conditioning stimulation train was repeated once
every 10 s and preceded the flexion reflex at different conditioning test (C-T) intervals,
measured as the time between the end of the pulse train delivered to the foot sole and the
beginning of the pulse train delivered to the sural nerve. The C-T intervals tested ranged from
3 to 90 ms (3, 6, 9, 15, 30, 60, 90 ms), so to observe short-and long-lasting effects of plantar
skin stimulation on the flexion reflex with hip positioned at different hip angles (10°, 30°

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flexion; 10° extension). These intervals were selected so to compare the effects on the flexion
reflex with the ones previously reported on the soleus H-reflex (Knikou 2005). For each control
and conditioned flexion reflex recorded in all subjects, a minimum of 15 reflex responses wereacquired every 10 s and saved for further analysis.
Experimental procedures
For the tests examining the modulation pattern of the flexion reflex, the hip was passively
flexed at 10°. Flexion reflexes recorded at this angle were considered to be the control reflexes.
Reflexes were subsequently recorded with the hip positioned randomly at 30° and at 40° of
flexion, at a neutral position (0°), and at 10° of extension. These flexion reflexes wereconsidered as the conditioned ones and were expressed as a percentage of the mean size of thecontrol reflex.

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In the second test, flexion reflexes were conditioned with plantar cutaneous afferent stimulation
at varying time delays with the hip positioned randomly at 10°, 30° of flexion, and at 10° of
extension. The stimulus strength evoking the control flexion reflex recorded at different hipangles (30° of flexion, 10° of extension) was carefully adjusted for these reflexes to have similar
amplitude with the control flexion reflex recorded with hip flexed at 10°. This allowed tocounteract the modulatory effects that hip angle changes have on the flexion reflex and thus
to compare the amount of facilitation/inhibition due to the conditioning stimulation across hipangles and subjects tested. The conditioned flexion reflexes were expressed as a percentage ofthe control flexion reflex recorded at each hip angle. Tests were completed in two different
experimental sessions and each session lasted about 2 h.
Data analysis
The digitized EMG signals were full-wave rectified and the size of the flexion reflexes (early
and/or late) were quantified by calculating the area under the EMG records corresponding to
the period between the onset latency and the point in time at which the response fell below 1.5
standard deviation of the baseline EMG activity. In all tests, the conditioned reflexes wereexpressed as a percentage of the associated control flexion reflex.
In the tests examining the effects of static hip angle changes on flexion reflex excitability, theconditioned flexion reflexes recorded with hip flexed (30°, 40°), extended (10°), and at a neutral
angle (0°) were expressed as a percentage of the mean size of the control flexion reflex recordedwith hip flexed at 10°. A one-way analysis of variance (ANOVA) and post hoc Bonferroni
tests were applied to the data to establish significant differences between control andconditioned reflexes.

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The conditioned flexion reflexes that utilized stimulation of plantar cutaneous afferents wereexpressed as a percentage of the mean size of the control reflex recorded at each hip angle
tested. For each subject, a one-way ANOVA along with post hoc Bonferroni tests were applied
to the data to establish significant differences between control and conditioned reflexes acrossdifferent C-T intervals at each hip angle. The mean size of the conditioned flexion reflex fromeach subject was then grouped according to the hip angle and the C-T interval investigated. A
two-way ANOVA with repeated measures was applied to the data to establish if changes in
the magnitude of the conditioned flexion reflex across hip angles and C-T intervals investigatedwere statistically significant different. For all statistical tests, alpha was set at 95% ofconfidence interval. The results are presented as mean values and standard error of the mean
(SEM).

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Results
Observations on the expression of the early and late flexion reflex

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Examples of the two different classes of flexion reflexes are illustrated in Fig. 1. In subject 3,
sural nerve stimulation at 7.4 (=RT), and at 9.2 mA induced both the early and the late flexion
reflex, with the latter showing an increase in magnitude and duration with increases in thestimulus intensity. Similarly, in subject 5, at the stimulation intensity of 10.4 (=RT) and 17.4
mA both early and late flexion reflexes were present. However, this was not the case for subject
10 (Fig. 1). In this subject, sural nerve stimulation at 16.2 mA (=RT) and at 17.5 mA induced
no early flexion reflex. The early flexion reflex was observed in three out of the ten subjects.
Based on the expression of the early flexion reflex, it was apparent that this response was not
regularly observed, whatever the stimulus intensity employed. The late flexion reflexes (>120ms) were consistently observed under all conditions tested in all ten subjects. The occurrenceof a late response was independent of whether or not an early response was present.
Effects of imposed hip angle changes on the flexion reflex

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An early flexion reflex (<100 ms) was present sporadically in three subjects (s3, s5, and s8)
during hip angle changes. In subjects 3 and 5, the early flexion reflex was depressed with hip
flexed at 30° and in neutral angle (0°), while with hip extended to 10° it was absent (ordepressed). Interestingly, the absence of the early component with hip extended at 10° in these
two subjects coincided with facilitation of the late flexion reflex. In contrast, in subject 8 theearly flexion reflex was equally depressed with hip either flexed (30°, 40°) or extended at 10°.
In Fig. 2a, the effects of controlled static hip angle changes on the late flexion reflex are
indicated for one subject (s7) with the hip flexed at 10°, 30°, and 40° and with the hip extended
at 10°. As illustrated in the EMG recordings, positioning the hip in flexion angles resulted indepression of the flexion reflex, while a significant facilitation of the reflex was induced when
the hip was extended to 10°.
Positioning the hip at different flexion and extension angles resulted in significant changes on
the size of the late flexion reflex compared to control reflex values obtained with hip flexed at
10°. No significant changes were observed in the magnitude of the reflex with the hip positioned
in neutral (0°) (Fig. 2). The late flexion reflex was reduced when the hip was positioned at 30°
and at 40° of flexion, reaching overall amplitudes of only 77 ± 5% and 70 ± 6% of the control
reflex values. In contrast, with the hip extended at 10°, the flexion reflex was significantly
increased compared to control reflex values, reaching a mean level of 190 ± 34% of control
reflex values (P<0.05). The amplitude of the conditioned flexion reflex across hip angles was
statistically significant different (P<0.05).

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Effects of plantar cutaneous stimulation on the flexion reflex during hip angle changes
In these tests, the early flexion reflex was sporadically observed across the three subjects (s3,s5, s8) resulting in no possible establishment of the conditioning effects of plantar cutaneousafferents excitation on the early flexion reflex during hip angle changes.
The late flexion reflex was present in all subjects following plantar cutaneous afferent
excitation at all hip joint angles tested. A summary of the induced changes on the late flexion
reflex is illustrated in Fig. 3. In this figure, each data point presents the average size of theconditioned flexion reflex of all subjects. Plantar cutaneous afferent stimulation delivered withhip extended to 10° resulted in no significant effects on the flexion reflex for C-T intervals that
ranged from 3 to 9 ms (Fig. 3a). In contrast, for the longer C-T intervals tested (15–90 ms) the
conditioned flexion reflex was facilitated. The reflex magnitude for these intervals ranged from118 ± 6% to 140 ± 9% of the control reflex (P<0.05). Similarly, with hip flexed at 30° (Fig.

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NIH-PA Author Manuscript3c) no significant effects on the flexion reflex were encountered for C-T intervals that ranged
from 3 to 30 ms, while at the C-T intervals of 60 and 90 ms the flexion reflex was facilitated.
Moreover, excitation of plantar cutaneous afferents with hip flexed at 10° induced nosignificant effects on the flexion reflexes for C-T intervals of 3, 6, and 9 ms (P>0.05) (Fig. 3b).
During the longer C-T intervals the flexion reflex was depressed compared to control reflex
values (Fig. 3b).

Discussion
The present work extends our previous observations that hip proprioceptors modulatesignificantly both the soleus H-reflex and the actions of spinal inhibitory interneurons inneurologically intact and in spinal-injured subjects (Knikou and Rymer 2002a, b; Knikou
2005 Knikou 2006). Current results suggest that hip proprioceptors are also able to strongly
modulate flexion reflex pathways. During concurrent tactile input from the plantar aspect of
the foot, hip proprioceptors interacted with the interneurons of the FRA pathway modulating
the magnitude of the flexion reflex. Finally, the two classes of the flexion reflex did not dependon the intensity employed to excite FRA, with the early response shown to be absent (ordepressed) in most subjects, suggesting that different interneuronal pathways might beinvolved during their expression.

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Observations on the two types of the flexion reflex
The incidence of the early flexion reflex was low (30%). This is in agreement with previous
observations in SCI subjects (Shahani and Young 1971; Roby-Brami and Bussel 1987; Knikou
and Conway 2005), and in spinal l-dopa-treated cats (Conway et al. 1987; Anden et al.
1966a). In the present study, the test reflex stimulus intensity was normalized to the thresholdof the first evoked TA EMG activity, whether this corresponded to the early or to the lateflexion reflex. Thus, the presence of the early flexion reflex was not related to the stimulus
intensity employed to excite the FRA. In addition, the late flexion reflex appeared
independently of the early reflex (see Fig. 1c).
Our findings support the notion that the early and the late flexion reflexes are transmitted via
different interneuronal pathways (Schomburg 1990). The irregularity of the appearance of theearly flexion reflex suggests that it might be suppressed following a SCI in humans, in a similarmanner to that reported for the acute and chronic spinal cats following l-dopa administration(Anden et al. 1966a, b).
Possible receptors contributing to the flexion reflex modulation during hip angle changes

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Based on the current experimental protocol, it is difficult to identify the afferents or the
receptors that contributed to the flexion reflex modulation during imposed hip angle changes.
Nonetheless, evidence from studies in both humans and lower vertebrates suggest that thecontribution of hip muscle spindle afferents responding to stretch cannot be ignored. Muscle
spindle afferents are considered as receptors for detecting limb position (Prochazka et al.
1989), with their static discharges known to depend on the amount of the muscle shorteningor lengthening (Ribot-Ciscar et al. 2003). These findings are in agreement with the reports ofpatients, stating that they can still detect the position of their hip after a total hip joint
replacement (Grigg et al. 1973).
Stretch-sensitive group II afferents, considered as part of the FRA system, have diverse actions
on both flexors and extensors in acute-spinal preparations at rest (reviewed in McCrea 2001).
During fictive locomotion, FRA stimulation including the group II afferents, enhances theongoing flexion or resets the step cycle to flexion (Schomburg et al. 1998), while changes in
hip position, presumably via activity in flexor muscle stretch receptors and mainly group II

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afferents entrain the step cycle during fictive locomotion (Kriellaars et al. 1994; Perreault etal. 1995; Hiebert et al. 1996). Although the above studies were conducted under dynamic
conditions, they signify the impact of hip flexor muscle spindle afferents in FRA spinal
pathways. To conclude, it is likely that muscle spindle afferents responding to stretch
contributed to the observed effects.
Interaction of hip proprioceptors with FRA pathways
Sustained changes in hip extension angle induced a significant facilitation of the late flexion
reflex, while hip flexion resulted in reflex depression. No significant effects on the magnitudeof the reflex were observed when the hip was positioned at a neutral angle (0°), when comparedto the control reflex recorded with hip flexed at 10°. Our results show that during an imposed
hip extension, the late flexion reflex magnitude increases, which is in line with the modulation
pattern of the flexion reflex reported previously in SCI subjects, in human infants during
walking, and in the spinal cat model (Conway and Best 1995; Pang and Yang 2000, 2001;
Grillner and Rossignol 1978).

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It is important to note that our studies rely on sustained changes in hip joint angle, and that theeffects of dynamic hip movement may be different. Further, reorganization of the flexion reflex
during assisted walking in human SCI might result in different response patterns. However, it
has recently been reported that imposed extension of the hip produces a hip flexion momentin SCI subjects lying supine (Steldt and Schmit 2004), and augments the swing phase during
body weight-assisted treadmill walking in human SCI (Dietz et al. 2002), suggesting thatsimilar afferent systems and neuronal mechanisms might be involved under static and dynamic
conditions.

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At this point, we should consider the possibility that if motoneuronal excitability is increasedby hip extension then any afferent input, regardless of origin, will be magnified. In this case,the question that arises is whether the effects of hip angle changes were mediated by changes
in motoneuronal excitability alone or whether hip proprioceptors influenced directly the
excitability of interneurons of the FRA pathway. In this respect, we observed that the twoclasses of the flexion reflex (early and late) were modulated differently during hip angle
changes. A depression of the early reflex was observed with hip angle changes, but was
independent of the hip angle (flexion vs. extension). In two of three subjects this reflex
component was absent (or depressed) with hip extended at 10°, when the associated late flexion
reflex was facilitated. Given that the early and late flexion reflex effects were different during
hip angle changes, this argues against a simple increase in motoneuronal excitability. Thisconclusion is further supported by the interaction of hip proprioceptors with spinal inhibitory
interneurons such as those of reciprocal Ia, presynaptic, and Ib inhibitory interneurons in spinalinjured man (Knikou 2005). Nonetheless, future studies using more detailed methods arenecessary to address the relative contribution of interneurons in the expression of the spinal
reflexes during static or dynamic imposed hip angle changes.
Based on our results and on the spinal origin of the late flexion reflex (Baldissera et al. 1981;
Roby-Brami and Bussel 1987), it is apparent that the effects of hip angle changes weretransmitted through spinal interneurons. The similar modulation pattern observed between thelate flexion reflex and the soleus H-reflex during hip angle changes in spinal-injured man(Knikou and Rymer 2002b) also indicate that key spinal interneuronal circuits interact
systematically depending on the direction of the movement.
Interaction of plantar cutaneous afferents and FRA during hip angle changes
The present study supports the significant actions of low-threshold plantar cutaneous afferents
on spinal reflex pathways in individuals with an established chronic SCI. Under static

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conditions, excitation of plantar cutaneous afferents with hip extended and flexed at 10°
resulted in a significant long lasting facilitation and inhibition of the late flexion reflex,
respectively. With the hip flexed at 30°, the late flexion reflex was facilitated during the longest
C-T intervals investigated (60 and 90 ms) (see Fig. 3).
We have previously shown that activation of low-threshold plantar cutaneous afferents withidentical stimulation parameters in the same SCI subjects induce only facilitatory effects on
the soleus H-reflex with the amount of reflex facilitation to depend on the hip angle (see Fig.
2 in Knikou 2005). Our findings agree well with the notion that cutaneous mechanoreceptors
access ‘alternative reflex pathways’ to flexors and extensors so to promote stance (Hagbarth
1952;Schomburg 1990;Burke 1990). Further, sural nerve stimulation and excitation of plantar
cutaneous afferents were both low-threshold, while the distances of the stimulation sites tospinal segmental levels associated with the flexion reflex were equivalent. Thus, we can assume
that the conduction time of the testing and conditioning stimuli were similar. Therefore, given
the long latency of the flexion reflex and the long duration of the C-T intervals tested, it islikely that the reflex modulation was mediated through long latency spinal networks, whichmight also be involved in the spinal locomotor centers.

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Low-threshold stimulation of the deep or plantar nerves during late flexion reflexes indecerebrate spinal cats injected with L-dopa is effective in terminating the flexor phase(Conway et al. 1995), verifying that the effects of cutaneous afferents on the FRA pathways
are of spinal origin. The demonstration that activation of plantar cutaneous afferents caninfluence differently the flexion reflex during controlled hip angle variations suggests thepresence of an interneuronal switch triggered by concurrent input from hip proprioceptors andcutaneous mechanoreceptors.

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Earlier studies have reported that stimulation of low-threshold sensory afferents induces abimodal excitability pattern in extensor motoneurons, for example, an early inhibition that isfollowed by a substantial late facilitation of the H-reflex (Delwaide et al. 1981). It was later
proposed that cutaneous input modulates transmission in presynaptic inhibitory pathways ofboth flexor and extensor group Ia afferents in man (Nakashima et al. 1990; Iles 1996). Studies
addressing similar effects in human SCI have shown that sural nerve stimulation exciting nonnociceptive afferents facilitates the ipsilateral TA H-reflex and decreases the heteronymous Ia
facilitation exerted from the quadriceps onto soleus α motoneurons (Roby-Brami and Bussel
1990). These findings suggest that FRA stimulation induces presynaptic inhibition oftransmission of Ia afferent terminals, and that cutaneous afferents from the foot have spinal
oligosynaptic or polysynaptic connections with the interneurons of the FRA pathway.
Nonetheless, a specific neuronal mechanism involved in the flexion reflex modulation under
the current experimental protocol cannot be established.
Further, plantar cutaneous afferents include mechanoreceptors mediating sensation of theapplied load (Kavounoudias et al. 2000) contributing to body posture awareness (Roll et al.
2002). However, given the lack of load input in the present experiments, modulation of thesepathways might be different under loading conditions. Thus, there is a need for future studies
to address spinal integration of these afferent signals to both flexors and extensors duringassisted walking in human SCI.
Possible effects of intersubject variability
The spinal lesions were classified as ASIA C in nine out of ten subjects with their injury levelto range from C5 to T9. Similarly, six out of the ten subjects were taking varying amounts ofantispastic medications at the time of the study. We found however no significant differencesin the magnitude of the conditioned flexion reflex across conditioning protocols whencomparing data from subjects on spasticity medications to those without medications (P>0.05).
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Nonetheless, the sample size for this comparison was small. The antispastic effect of baclofen,
for example, on the expression of long-latency flexion reflex pathways has not been identified.
Thus, the study of such effects is an important topic for future studies since hip proprioceptive
input influences walking in individuals with SCI (Dietz et al. 2002).
Conclusions and considerations for SCI rehabilitation
The late flexion reflex in human SCI has been compared with the late flexion reflex observedin l-dopa-treated acute and chronic spinal cats (Roby-Brami and Bussel 1990, 1992; Anden etal. 1966a, b). This reflex in the cat and in man is considered to utilize interneurons of spinal
locomotor centers (Lundberg 1979; Baldissera et al. 1981; Bussel et al. 1989). Our findings
demonstrate that the late flexion reflex in spinal-injured man is influenced by afferent feedback
from both cutaneous mechanoreceptors and hip proprioceptors.
Flexion reflexes are also utilized to promote the swing phase of gait during functional electricalstimulation (FES)-assisted walking in individuals with a SCI (Postans et al. 2004). In this set
up, the flexion reflex provides a synchronized flexion movement of hip, knee, and ankle
promoting the swing phase of gait. It is thus advisable for optimizing this intervention FRA
excitation to occur before the hip has reached a neutral angle.

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In the light of the emerging new findings during body weight-assisted treadmill walking(Harkema 2001), employed alone or in combination with FES utilizing the flexion reflex toassist stepping after SCI, and that the influence of plantar sensitivity on postural control islikely to increase in a neurological disorder (Meyer et al. 2004), the activity of theseinterneuronal pathways should be further investigated during assisted walking in motor
incomplete SCI patients, thus afferent input of proper amplitude and time be present during
their locomotor training.
Acknowledgements
Authors are in debt to the subjects for their willingness to participate on many hours of experimentation throughout
the project. This study was supported by the National Institute of Child Health and Human Development (NICHD),
National Institutes of Health (NIH), Grant No. 5R03HD43951 (MK).

References

NIH-PA Author Manuscript

Anden NE, Jukes MG, Lundberg A, Vyklicky L. The effect of Dopa on the spinal cord 1. Influence ontransmission from primary afferents. Acta Physiol Scand 1966a;67:373–386. [PubMed: 5967601]
Anden NE, Jukes MG, Lundberg A. The effect of Dopa on the spinal cord. 2. A pharmacological analysis.
Acta Physiol Scand 1966b;67:387–397. [PubMed: 5967602]
Anden NE, Jukes MG, Lundberg A, Vyklicky L. The effect of Dopa on the spinal cord. 3. Depolarization
evoked in the central terminals of ipsilateral Ia afferents by volleys in the FRA. Acta Physiol Scand
1966c;68:322–336.
Andersen OK, Sonnenborg FA, Arendt-Nielsen L. Modular organization of human leg withdrawal
reflexes elicited by electrical stimulation of the foot sole. Muscle Nerve 1999;22:1520–1530.
[PubMed: 10514229]
Ashworth B. Preliminary trial of carisoprodol in multiple sclerosis. Practioner 1964;192:540–542.
Baldissera F, Hultborn H, Illert M (1981) Integration in spinal neuronal systems. In: Handbook ofphysiology, the nervous system II, pp 509–595
Baxendale RH, Ferrell WR. The effect of knee joint discharge on transmission in flexion reflex pathways
in decerebrate cats. J Physiol (Lond) 1981;315:231–242. [PubMed: 7310709]
Bouyer LJG, Rossignol S. Contribution of cutaneous inputs from the hindpaw to the control oflocomotion. II. Spinal cats. J Neurophysiol 2003;90:3640–3653. [PubMed: 12944535]
Burke D. Exteroceptive reflexes and flexor spasms. Adv Neural Regenerat Res 1990:379–389.

Exp Brain Res. Author manuscript; available in PMC 2006 February 6.

Knikou et al.

Page 11

NIH-PA Author Manuscript
NIH-PA Author Manuscript
NIH-PA Author Manuscript

Bussel B, Roby-Brami A, Yakovleff A, Bernis N. Late flexion reflex in paraplegic patients: evidence fora spinal stepping generator. Brain Res Bull 1989;22:53–56. [PubMed: 2653569]
Conway BA, Hultborn H, Kiehn O. Proprioceptive input resets central locomotor rhythm in the spinal
cat. Exp Brain Res 1987;68:643–656. [PubMed: 3691733]
Conway BA, Best N. The effect of changes in static hip position on the flexion reflex in motor complete
spinal cord injured humans. J Physiol Suppl 1995;487:75–76.
Conway BA, Scott DT, Riddell JS (1995) The effects of plantar nerve stimulation on long latency flexion
reflexes in the acute spinal cat. In: A. Taylor, M.N. Gladden, R. Durbada (eds) Alpha and gamma
motor systems. Plenum Press, pp. 593–595
Delwaide PJ, Crenna P, Fleron MH. Cutaneous nerve stimulation and motoneuronal excitability. I: Soleus
and tibialis anterior excitability after ipsilateral and contralateral sural nerve stimulation. J Neurol
Neurosurg Psychiatry 1981;44:699–707. [PubMed: 7299408]
Dietz V, Wirtz M, Curt A, Colombo G. Locomotor pattern in paraplegic patients: training effects recoveryof spinal cord function. Spinal Cord 1998;36:380–390. [PubMed: 9648193]
Dietz V, Muller R, Colombo G. Locomotor activity in spinal man: significance of afferent input fromjoint and load receptors. Brain 2002;125:2626–2634. [PubMed: 12429590]
Dimitrijevic MR, Nathan PW. Studies of spasticity in man. 3. Analysis of reflex activity evoked by
noxious cutaneous stimulation. Brain 1968;91:349–368. [PubMed: 5721935]
Duysens J, Pearson KG. The role of cutaneous afferents from the distal hindlimb in the regulation of thestep cycle of thalamic cats. Exp Brain Res 1976;24:245–255. [PubMed: 1253857]
Duysens J. Reflex control of locomotion as revealed by stimulation of cutaneous afferents inspontaneously walking premammillary cats. J Neurophysiol 1977;40:737–751. [PubMed: 886369]
Eccles JC, Lundberg A. Synaptic actions in motoneurones by afferents which may evoke the flexion
reflex. Arch Ital Biol 1959;97:199–221.
Fuhrer MJ. Interstimulus interval effects on habituation of flexor withdrawal activity mediated by thefunctionally transected human spinal cord. Arch Phys Med Rehabil 1976;57:577–582. [PubMed:
999483]
Grillner S, Rossignol S. On the initiation of the swing phase of locomotion in chronic spinal cats. Brain
Res 1978;146:269–277. [PubMed: 274169]
Grillner S (1981) Control of locomotion in bipeds, tetrapods, and fish. In: Brooks VB (ed) Handbook ofphysiology: the nervous system: motor control, Vol. 2. Am. Physiol. Soc. Bethesda, pp. 1179–1236
Grigg P, Finerman GA, Riley LH. Joint-position sense after total hip replacement. J Bone J Surg
1973;55:1016–1025.
Hagbarth KE. Excitatory and inhibitory skin areas for flexor and extensor motoneurones. Acta Physiol
Scand Suppl 1952;94:1–57. [PubMed: 14943559]
Hagbarth KE, Finer BL. The plasticity of human withdrawal reflexes to noxious skin stimuli in lower
limbs. Prog Brain Res 1963;1:65–81.
Harkema SJ. Neural plasticity after human spinal cord injury: applications of locomotor training to therehabilitation of walking. Prog Clin Neurosci 2001;7:455–468.
Hiebert GW, Whelan PJ, Prochazka A, Pearson KG. Contribution of hind limb flexor muscle afferents
to the timing of phase transitions in the cat step cycle. J Neurophysiol 1996;75:1126–1137. [PubMed:
8867123]
Hultborn H, Illert M (1991) How is motor behavior reflected in the organization of spinal systems. In:
Humphrey DR, Freud HJ (eds) Motor control: concept and issues, Wiley, New York, pp.49–73
Iles JF. Evidence for cutaneous and corticospinal modulation of presynaptic inhibition of Ia afferents
from the human lower limb. J Physiol (Lond) 1996;491:197–207. [PubMed: 9011611]
Jankowska E, Jukes MGM, Lund S, Lundberg A. The effect of DOPA on the spinal cord. 5. Reciprocalorganization of pathways transmitting excitatory action to alpha motoneurones of flexors andextensors. Acta Physiol Scand 1967a;70:369–388. [PubMed: 4293473]
Jankowska E, Jukes MGM, Lund S, Lundberg A. The effect of DOPA on the spinal cord. 6. Half centreorganization of interneurones transmitting effects from the flexor reflex afferents. Acta Physiol Scand
1967b;70:389–402. [PubMed: 4294400]

Exp Brain Res. Author manuscript; available in PMC 2006 February 6.

Knikou et al.

Page 12

NIH-PA Author Manuscript
NIH-PA Author Manuscript
NIH-PA Author Manuscript

Kavounoudias A, Roll R, Roll J-P. Foot sole and ankle muscle inputs contribute jointly to human erect
posture regulation. J Physiol (Lond) 2001;532:869–878. [PubMed: 11313452]
Kernell D, Hultborn H. Synaptic effects on recruitment gain: a mechanism of importance for the inputoutput relations of motoneurone pools. Brain Res 1990;507:176–179. [PubMed: 2302576]
Knikou M, Rymer WZ. Effects of changes in hip joint angle on H-reflex excitability in humans. [Erratumin Exp Brain Res (2002) 144:558]. Exp Brain Res 2002a;143:149–159. [PubMed: 11880891]
Knikou M, Rymer WZ. Hip angle induced modulation of H reflex amplitude, latency and duration in
spinal cord injured humans. Clin Neurophysiol 2002b;113:1698–1708. [PubMed: 12417222]
Knikou M (2005) Effects of hip joint angle changes on intersegmental spinal coupling in human spinal
cord injury. Exp Brain Res DOI: 10.1007/s00221-005-0046-6, published online on July 30, 2005
Knikou M, Conway BA (2005) Effects of electrically induced muscle contraction on flexion reflex inhuman spinal cord injury. Spinal Cord DOI: 10.1038/sj.sc.3101772
Knikou M, Rymer WZ, Kay E (2005) Hip proprioceptors interact with plantar cutaneous afferents
modulating the flexion reflex in human spinal cord injury. Abstract Viewer/Itinerary Planner.
Washington, DC: Society for Neuroscience
Knikou M. Effects of changes in hip position on actions of spinal inhibitory interneurons in humans. Int
J Neurosci 2006;116(6)in press
Kriellaars DJ, Brownstone RM, Noga BR, Jordan LM. Mechanical entrainment of fictive locomotion in
the decerebrate cat. J Neurophysiol 1994;71:2074–2086. [PubMed: 7931503]
Lundberg A (1979) Multisensory control of spinal reflex pathways. In: R. Granit O. Pomeiano (ed),Reflex control of posture and movement. Elsevier, Amsterdam, pp 11–28
Maynard FM, Bracken MB, Creasey G, Ditunno JF, Donovan WH, Ducker TB, Garber SL, Marini RJ,
Stover SL, Tator CH, Waters RL, Wilberger JP, Young W. International standards for neurologicaland functional classification of spinal cord injury. Spinal Cord 1997;5:266–274. [PubMed: 9160449]
McCrea DA. Spinal circuitry of sensorimotor control of locomotion. J Physiol (Lond) 2001;533:41–50.
[PubMed: 11351011]
Meinck H-M, Kuster S, Benecke R, Conrad B. The flexor reflex-influence of stimulus parameters on thereflex response. Electroencephalogr Clin Neurophysiol 1985;61:287–298. [PubMed: 2411507]
Meyer PF, Oddsson LI, De Luca CJ. The role of plantar cutaneous sensation in unperturbed stance. Exp
Brain Res 2004;156:502–512.
Nakashima K, Rothwell JC, Day BL, Thompson PD, Marsden CD. Cutaneous effects on presynaptic
inhibition of flexor Ia afferents in the human forearm. J Physiol (Lond) 1990;426:369–380. [PubMed:
2172516]
Pang M, Yang JF. The initiation of the swing phase in human infant stepping: importance of hip positionand leg loading. J Physiol (Lond) 2000;528:389–404. [PubMed: 11034628]
Pang M, Yang JF. Interlimb co-coordination in human infant stepping. J Physiol (Lond) 2001;533:617–
625. [PubMed: 11389217]
Perreault M-C, Angel MJ, Guertin P, McCrea DA. Effects of stimulation of hindlimb flexor group II
afferents during fictive locomotion in the cat. J Physiol (Lond) 1995;487:211–220. [PubMed:
7473250]
Postans NJ, Hasler JP, Granat MH, Maxwell DJ. Functional electric stimulation to augment partial
weight-bearing supported treadmill training for patients with acute incomplete spinal cord injury: apilot study. Arch Phys Med Rehabil 2004;85:604–610. [PubMed: 15083437]
Prochazka A, Trend PSJ, Hulliger M, Vincent S. Ensemble proprioceptive activity in the cat step cycle:
towards a representative look-up chart. Prog Brain Res 1989;80:61–74. [PubMed: 2634286]
Ribot-Ciscar E, Bergenheim M, Albert F, Roll J-P. Proprioceptive population coding of limb position inhumans. Exp Brain Res 2003;149:512–519. [PubMed: 12677332]
Roby-Brami A, Bussel B. Long latency spinal reflex in man after flexor reflex afferent stimulation. Brain
1987;110:707–725. [PubMed: 3107749]
Roby-Brami A, Bussel B. Effects of FRA stimulation on the soleus H-reflex in patients with a complete
spinal cord lesion: evidence for presynaptic inhibition of Ia transmission. Exp Brain Res
1990;81:593–601. [PubMed: 2171974]

Exp Brain Res. Author manuscript; available in PMC 2006 February 6.

Knikou et al.

Page 13

NIH-PA Author Manuscript

Roby-Brami A, Bussel B. Inhibitory effects on flexor reflexes in patients with a complete spinal cordlesion. Exp Brain Res 1992;90:201–208. [PubMed: 1521608]
Roll R, Kavounoudias A, Roll J-P. Cutaneous afferents from human plantar sole contribute to body
posture awareness. NeuroReport 2002;13:1957–1961. [PubMed: 12395099]
Schomburg ED. Spinal sensorimotor systems and their supraspinal control. Neurosci Res 1990;7:265–340. [PubMed: 2156196]
Schomburg ED, Petersen N, Barajon I, Hultborn H. Flexor reflex afferents reset the step cycle during
fictive locomotion in the cat. Exp Brain Res 1998;122:339–350. [PubMed: 9808307]
Shahani BT, Young RR. Human flexor reflexes. J Neurol Neurosurg Psychiatry 1971;34:616–627.
[PubMed: 5122389]
Sherrington CS. Flexion-reflex of the limb, crossed extension-reflex and reflex stepping and standing. J
Physiol (Lond) 1910;40:28–121. [PubMed: 16993027]
Steldt RE, Schmit BD. Modulation of coordinated muscle activity during imposed sinusoidal hip
movements in human spinal cord injury. J Neurophysiol 2004;92:673–685. [PubMed: 15044520]
Thomas CK, Westling G. Tactile unit properties after human cervical spinal cord injury. Brain
1995;118:1547–1556. [PubMed: 8595483]

NIH-PA Author Manuscript
NIH-PA Author Manuscript
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Fig. 1.

The full-wave rectified EMG averages of the two classes of the flexion reflex are identified byvertical cursors placed at the start and at the end of the corresponding EMG burst. For all threesubjects, the top EMG corresponds to the stimulation intensity during which a response in thetibialis anterior muscle was first observed. In subject 10 (c), the early flexion reflex was absent
when the sural nerve was stimulated at non-nociceptive stimulus intensities

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Fig. 2.

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Effects of imposed static hip angle changes on the late flexion reflex.(a) The average lateflexion reflex recorded with the ipsilateral hip set at 10° of flexion (control hip angle), 30° of
flexion, 40° of flexion and at 10° of extension for one subject (s7) is presented. (b) Pool data
showing the effects of hip angle variations on the late flexion reflex. For each hip angle tested,
the average size of the conditioned late flexion reflexes (as a percentage of the control lateflexion reflex recorded with hip flexed at 10°) was calculated for all subjects tested.
Asterisks indicate cases of statistically significant differences between the control and theconditioned reflex sizes (P<0.05). Error bars indicate the SEM

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Fig. 3.

Time course of the effects of plantar cutaneous afferent excitation on the late flexion reflex
with hip positioned at 10° of extension (a), 10° of flexion (b), and at 30° of flexion (c). For
each conditioning test interval, the overall average size of the conditioned late flexion reflex
is presented as a percentage of the associated control flexion reflex recorded at each hip angle
tested. Asterisks indicate statistically significant differences between the conditioned and thecontrol flexion reflex (P<0.05). Error bars represent the SEM

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M
M
M
M
M
F
M
M
M
M

S1
S3
S4
S5
S6
S7
S8

S9
S10

S11

50

42
50

23
27
45
20
17
59
15

Postinjury (months)

162

38
186

78
26
54
21
27
26
26

3

0
1

1
0
2
2
0
0
2

Ashworth score

C

C
C

C
C
C
C
D
C
C

ASIA scale

C5

C8
C5

C5
C5
C6
T11
C6
T9
T3

Lesion level

IntactIntactIntactIntactIntactIntactNo sensation ofcold/warm
IntactNo sensation ofcold/warm
No sensation ofcold/warm

Sensation-

Plavix Lipotor 75 mg
Baclofen 30 mg

Baclofen 60 mg
Baclofen 20 mg
Baclofen 20 mg
Baclofen 10 mg-

Medication/day

Spasticity at the ankle was scaled according to the Ashworth scale (Ashworth 1964). The completeness of the lesion was classified according to the American Spinal Injury Association (ASIA) scale(Maynard et al. 1997), and represents ASIA B: motor complete but sensory incomplete; ASIA C: sensory and motor incomplete, but with more than half of the muscles below injury level having a
muscle grade of less than 3 out of 5, and ASIA D: sensory and motor incomplete with at least half of the muscles below the level of the injury having a muscle grade of 3 or higher. F, Female; M,
Male.

GenderAge (years)

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Subjects

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Table 1

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SCI subjects’ characteristics
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