Expansion of nociceptive withdrawal reflex receptive fields in spinal cord injured humans

OBJECTIVE: In spinal cord injured (SCI) subjects, exaggerated withdrawal reflexes associated with a dominant flexor pattern irrespective of stimulation site have been reported. In the present study, withdrawal reflex receptive field (RRF) was determined in complete SCI subjects (N=9). METHODS: Distributed electrical stimulation was applied to the sole of the foot, and reflexes in tibialis anterior, soleus, biceps femoris, and vastus lateralis muscles were recorded together with knee and ankle movement trajectories. A group of spinally intact subjects (N=10) were included as controls. With the subjects in supine position, stimulation was applied to 10 different sites on the foot sole. Based on the tibialis anterior reflex threshold for stimulation on the mid foot sole, two stimulus intensities (1.1 times the reflex threshold and 1.4 times the reflex threshold) were used for all 10 sites. RESULTS: In SCI subjects, dorsi-flexion dominated independent of stimulus site and the tibialis anterior RRF covered the entire foot sole in contrast to a well-defined tibialis anterior receptive field at the medial, distal foot sole in the spinally intact subjects. Further, the soleus RRF also covered the entire sole in the SCI subjects. The reflexes in biceps femoris and vastus lateralis muscles were small and associated with weak knee flexion at all 10 sites in the SCI subjects and in the controls. CONCLUSIONS: The RRF of the ankle flexor and the ankle extensor muscles both covered the entire sole of the foot indicating an expansion of the RRFs following spinal cord injury. The expansion is most likely due to lack of descending inhibitory control and/or increased sensitivity of the spinal reflex loop in the SCI subjects. SIGNIFICANCE: The study improves the understanding of spinal reflex control in spinal intact and spinal cord injured subjects.     

Reflex receptive fields for human withdrawal reflexes elicited by non-painful and painful electrical stimulation of the foot sole.

OBJECTIVES: Human withdrawal reflex receptive fields (RRFs) were assessed for 4 different electrical stimulus intensities, ranging from below the pain threshold (PTh) to up to two times the PTh intensity (0.8x, 1.2x, 1.6x, and 2.0xPTh). METHODS: Thirteen subjects participated, and the reflexes were recorded in a sitting position. The stimuli were delivered in random order to 12 positions distributed over the foot sole. Tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL), and biceps femoris (BF) reflexes were recorded. Further, knee and ankle joint angle changes were recorded. RESULTS: The strongest reflexes were seen in the TA compared with the other 3 muscles. Dorsi-flexion dominated distal to the talocrural joint corresponding to the TA receptive field area. An expansion of the RRF for the TA and GM was seen when increasing the stimulus intensity from 0.8xPTh to 1.2xPTh and from 1.2xPTh to 1.6xPTh, indicating a gradually increasing reflex threshold towards the border, where TA contraction is inappropriate in a withdrawal reaction. For the BF and VL, the borders of the RRF areas were not detected. By integrating the reflex size within the RRF (i.e. the reflex volume), gradually increasing reflexes for increasing stimulus intensity were seen in all 4 muscles tested, most clearly in the TA and GM. The subjective pain intensity correlated to the reflex volume for the TA, GM, and BF. CONCLUSIONS: In conclusion, the highest reflex sensitivity was seen in the centre of the RRF, while the stimulus intensity needed for eliciting a reflex increased towards the receptive field border. Within the RRF, stronger reflexes were evoked for increasing stimulus intensity. The limit in the size of the receptive field size for the TA and GM supports a modular withdrawal reflex organisation.     

Modular organization of human leg withdrawal reflexes elicited by electrical stimulation of the foot sole.

Human withdrawal reflex receptive fields were determined for leg muscles by randomized, electrical stimulation at 16 different positions on the foot sole. Tibialis anterior, gastrocnemius medialis, peroneus longus, soleus, rectus femoris, and biceps femoris reflexes, and ankle joint angle changes were recorded from 14 subjects in sitting position. Tibialis anterior reflexes were evoked at the medial, distal foot and correlated well with ankle dorsal flexion. Gastrocnemius medialis reflexes were evoked on the heel and correlated with plantar flexion. Stimulation on the distal, medial sole resulted in inversion (correlated best with tibialis anterior activity), whereas stimulation of the distal, lateral sole evoked eversion. Biceps femoris reflexes were evoked on the entire sole followed by a small reflex in rectus femoris. A detailed withdrawal reflex organization, in which each lower leg muscle has its own receptive field, may explain the ankle joint responses. The thigh activity consisted primarily of flexor activation.     

Nociceptive withdrawal reflexes evoked by uniform-temperature laser heat stimulation of large skin areas in humans

Nociceptive withdrawal reflexes (NWR) were evoked by brief (200 ms) painful CO(2) laser stimulation at five intensities (1.2, 1.4, 1.6, 1.8, and 2.0 x pain threshold) applied to nine sites (2 cm(2)) separated by 1.7 cm on the dorsal side of the foot and anterior part of the lower leg of 14 healthy volunteers. The purpose of the study was to investigate the characteristics of NWRs evoked by a natural stimulation modality. The reflexes were measured as the electromyographic response from the iliopsoas (ILI), quadriceps vastus lateralis (QVL), biceps femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles. Stimulus-response relationships between heat intensity and the reflex magnitude and correlation between perceived pain intensity and reflex magnitude were observed in the ILI, QVL, BF, and TA but not the SOL. No significant differences in reflex magnitude were found between the stimulation sites. NWRs were evoked more often in flexor muscles than extensor muscles, indicating a non-site-specific reflex organization. The paper presents a new method to evoke NWRs by uniform-temperature laser heat stimulation of large skin areas in humans. These heat evoked reflexes had a stimulus-response relationship.     

Gradual enlargement of human withdrawal reflex receptive fields following repetitive painful stimulation

Dynamic changes in the topography of the human withdrawal reflex receptive fields (RRF) were assessed by repetitive painful stimuli in 15 healthy subjects. A train of five electrical stimuli was delivered at a frequency of 3 Hz (total train duration 1.33 s). The train was delivered in random order to 10 electrode sites on the sole of the foot. Reflexes were recorded from tibialis anterior, soleus, vastus lateralis, biceps femoris, and iliopsoas (IL). The RRF changes during the stimulus train were assessed during standing with even support on both legs and while seated. The degree of temporal summation was depending on stimulation site. At the most sensitive part of the RRF, a statistically significant increase in reflex size was seen after two stimuli while four stimuli were needed to observe reflex facilitation at less sensitive electrode sites. Hence, the region from which reflexes could be evoked using the same stimulus intensity became larger through the train, that is, the RRF was gradually expanding. Reflexes evoked by stimuli four and five were of the same size. No reflex facilitation was seen at other stimulus sites outside the RRF. In all muscles except in IL, the largest reflexes were evoked when the subjects were standing. In the ankle joint, the main withdrawal pattern consisted of plantar flexion and inversion when the subjects were standing while dorsi-flexion was prevalent in the sitting position. Up to 35 degrees of knee and hip flexion were evoked often leading to a lift of the foot from the floor during standing. In conclusion, a gradual expansion of the RRF was seen in all muscles during the stimulus train. Furthermore, the motor programme task controls the reflex sensitivity within the reflex receptive field and, hence, the sensitivity of the temporal summation mechanism.     

Modulation of human short latency reflexes between standing and walking

Inhibition of the magnitude of soleus muscle homonymous (H) reflexes occurs in humans when walking, compared to standing. The current study asked, (1) was the task modulation of Ia reflexes limited to soleus muscle, (2) was there support for attributing a presynaptic source to the inhibition in humans and (3) did an oligosynaptic short latency reflex show similar task modulation? In 3 subjects, H reflexes were evoked in vastus medialis and soleus, at 4 levels of contraction in the target muscle, with constant stimulus intensity when walking and standing. The reflex magnitudes in both muscles were significantly inhibited during the contractions for walking, compared to standing. Such inhibition also occurred in H reflexes of tibialis anterior muscle. An excitatory oligosynaptic reflex was then evoked in vastus medialis, through low intensity stimulation of the common peroneal nerve during walking and standing. The mean amplitudes of this reflex were not significantly different (P less than 0.05) between the two conditions, at any contraction level. The depression of quadriceps H reflexes, compared to the oligosynaptic reflexes through the same quadriceps motoneuronal pool in the same task, strongly suggested that the inhibition of H reflexes arose at other sites besides the motoneuronal cell body and proximal dendrites. We conclude that Ia H reflexes of various leg muscles of humans are inhibited when walking but that this does not generalize to the oligosynaptic short latency reflex between the anterior shank and thigh.     

Differential Effects of a Distant Noxious Stimulus on Hindlimb Nociceptive Withdrawal Reflexes in the Rat

Recent studies indicate that the nociceptive withdrawal reflexes to individual muscles are evoked by separate reflex pathways. The present study examines whether nociceptive withdrawal reflexes to different muscles are subject to differential supraspinal control in rats. A distant noxious stimulus was used to activate a bulbospinal system which selectively inhibits 'multireceptive' neurons (i.e. neurons receiving excitatory tactile and nociceptive inputs) in the dorsal horn of the spinal cord. Withdrawal reflexes, recorded with electromyographic techniques in single hindlimb muscles, were evoked by standardized noxious pinch. Thirty-seven rats, anaesthetized with halothane and nitrous oxide, were used. Whereas withdrawal reflexes to the extensor digitorum longus and brevis, tibialis anterior and biceps posterior muscles were strongly inhibited, reflexes to interossei muscles were potentiated during noxious pinch of the nose. Reflexes to peronei muscles were not significantly changed. The effects on the reflexes usually had an onset latency of <0.5 s and outlasted the conditioning stimulation by up to 2 s. The monosynaptic la reflex to the deep peroneal nerve, innervating dorsiflexors of the digits and ankle, was not significantly changed during noxious pinch of the nose. Hence, the inhibitory effects on the hindlimb withdrawal reflexes induced by the conditioning stimulation were presumably exerted on reflex interneurons. It is concluded that nociceptive withdrawal reflexes to different hindlimb muscles are differentially controlled by descending pathways activated by a distant noxious stimulus. The results support our previous conclusion that there are separate nociceptive withdrawal reflex pathways to different hindlimb muscles.     

Tibialis Anterior and Soleus Withdrawal Reflexes Elicited by Electrical Stimulation of the Sole of the Foot during Gait

The aim of the present study was to investigate the modulation and functional importance of nociceptive withdrawal reflexes elicited from the sole of the foot and recorded from the soleus (SOL) and tibialis anterior (TA) muscles during gait. Cutaneous electrical stimulation delivered at four locations of the sole of the foot was used to elicit the withdrawal reflex. Reflexes were recorded from eight healthy subjects during treadmill walking. The reflexes were elicited at heel‐contact, during foot‐flat, at heel‐off, and during mid‐swing. The reflexes evoked in TA were largest when the arch of the foot was stimulated, and smallest following stimulation of the heel (significant difference during stance, p ≤ 0.002). The largest soleus responses were elicited when the arch of the foot was stimulated (significant difference compared with the fifth metatarsophalangeal joint, stimulation after heel‐contact, p < 0.05). The TA reflex, expressed as a proportion of the electromyogram during unperturbed gait, was smallest during swing (p < 0.05, compared with stance) whereas the SOL reflex was maximal during swing (p < 0.05, compared with stance). The results suggest that the modulation of the reflex promotes an appropriate withdrawal while preserving balance and continuity of motion. These results may have applications in assisting gait of hemiplegics.     

H-reflex modulation during walking in spastic paretic subjects.

Hoffman (H) reflexes were elicited from the soleus muscle during treadmill walking in 21 spastic paretic patients. The soleus and tibialis anterior muscles were reciprocally activated during walking in most patients, much like that observed in healthy individuals. The pattern of H-reflex modulation varied considerably between patients, from being relatively normal in some patients to a complete absence of modulation in others. The most common pattern observed was a lack of H-reflex modulation through the stance phase and slight depression of the reflex in the swing phase, considerably less modulation than that of normal subjects under comparable walking conditions. The high reflex amplitudes during periods of the step cycle such as early stance seems to be related to the stretch-induced large electromyogram bursts in the soleus in some subjects. The abnormally active reflexes appear to contribute to the clonus encountered during walking in these patients. In three patients who were able to walk for extended periods, the effect of stimulus intensity was examined. Two of these patients showed a greater degree of reflex modulation at lower stimulus intensities, suggesting that the lack of modulation observed at higher stimulus intensities is a result of saturation of the reflex loop. In six other patients, however, no reflex modulation could be demonstrated even at very low stimulus intensities.     

Can Ib axons be selectively activated by electrical stimuli in human subjects?

A tendon-vibration technique, used to raise the electrical threshold of muscle spindle Ia afferent fibers above that of Golgi tendon organ Ib afferent fibers in animals, was tested on human subjects. After prolonged tendon vibration, electrical stimulation of the posterior tibial nerve was ineffective or markedly less effective in eliciting Hoffmann (H-) reflexes in the soleus muscle at previbration threshold intensities. With stimulus intensity held constant at values between 1.0 to 1.4 X threshold, postvibration H-reflex myoelectric amplitudes returned to previbration values usually within 60 min. However, at higher electrical stimulus intensities (1.8 X threshold), postvibration H-reflex amplitudes were produced at or near previbration values irrespective of postvibration recovery time; in contrast, initial postvibration tendon tap reflexes were potentiated. Findings suggest that it is indeed possible to selectively activate Ib afferent fibers in humans by electrical stimuli.     

Effects of femoral nerve stimulation on the electromyogram and reflex excitability of tibialis anterior and soleus

The present study was undertaken to determine whether femoral nerve stimulation would produce heteronymous reflex responses in tibialis anterior (TA) and soleus, demonstrable by averaging the electromyogram (EMG) produced by a voluntary contraction, and whether the responsible changes in excitability were sufficient to affect the H reflexes of TA and soleus. In both muscles, femoral stimuli produced short-latency, presumably monosynaptic excitation, better defined in poststimulus averages of unrectified EMG, followed by long-lasting inhibition, better defined in averaged rectified traces. The H reflexes underwent changes at appropriate latencies. The thresholds for excitation and inhibition were, respectively, below and above threshold for the quadriceps M wave. The heteronymous responses were largely independent of stimulus rate and, within limits, scaled with the level of background contraction. The ability to define these heteronymous connections using relatively simple methodology extends their utility. Such tests may prove useful in probing pathophysiological mechanisms in individual patients. © 1996 John Wiley & Sons, Inc.     

Somatovesical and vesicovesical excitatory reflexes in urethane-anaesthetized rats

The effect of spinal cord transection on excitatory somato- and vesicovesical micturition reflexes have been investigated in urethane-anaesthetized rats. In adult rats, 3 distinct types of excitatory reflexes to the bladder may be observed: a somatovesical reflex organized at spinal level and two vesicovesical reflexes organized at spinal and supraspinal level, respectively. In agreement with results of lesion experiments (Neurosci. Lett., 8 (1978) 27-33), bladder voiding is abolished following spinal cord transection although both somato- and vesicovesical reflexes may be demonstrated in acute spinal rats. Occurrence of the spinal vesicovesical reflex during the collecting phase of the cystometrogram appears to be inhibited by a supraspinal inhibitory pathway.     

Modulation of the withdrawal reflex during hemiplegic gait: effect of stimulation site and gait phase.

OBJECTIVE: The objective of the study was to investigate the sensitivity of the nociceptive withdrawal reflex to stimulation of different locations on the sole of the foot during hemiplegic gait. METHODS: Reflexes were evoked by cutaneous electrical stimulation of 4 locations on the sole of the foot of 7 hemiplegic and 6 age-matched healthy persons. The stimuli were delivered at heel-contact, during foot-flat, at heel-off, and during mid-swing. Reflexes were recorded from muscles of the stimulated and the contralateral leg. Ankle, knee, and hip joints angles were recorded using goniometers. RESULTS: In the hemiplegic persons, the size of tibialis anterior reflexes, and the latency of soleus reflexes were site- and phase-modulated. In both groups, the tibialis anterior reflexes were significantly smaller with stimulation to the fifth metatarsophalangeal joint and the heel compared with the first metatarsophalangeal joint and the arch of the foot. The tibialis anterior reflexes evoked at heel-off and mid-swing were larger in hemiplegic persons than in healthy persons. Reflexes in the proximal and contralateral limb muscles were not site-modulated during hemiplegic gait. The kinematic response at the ankle joint was also different in the two groups during mid-swing. CONCLUSIONS: Hemiplegic and healthy middle-aged people presented different phase-modulation of the kinematic and muscle nociceptive reflex responses evoked by stimulation delivered on the sole of the foot. SIGNIFICANCE: The results have potential application in programs to rehabilitate hemiplegic gait.     

Tendon vibration-induced inhibition of human and cat triceps surae group I reflexes: evidence of selective Ib afferent fiber activation

In humans, prolonged vibration of the Achilles tendon produced transient depression or abolition of the soleus H-reflex. Recovery of the electrical reflex threshold to previbration values at a constant lower stimulus intensity usually occurred between 10 to 55 min. Electrical stimulation at higher multiples of the reflex threshold produced reflex EMG amplitudes more immediately comparable to previbration controls. When postvibration H-reflexes were completely abolished, poststimulus averaging of voluntarily maintained tonic EMG activity showed evidence of inhibition at a 46-ms latency in contrast to a 32-ms previbration H-reflex latency. In cat, observation of H-reflexes were rare, but stimulus-evoked changes in EMG activity mimicked the postvibration depression seen in humans. Ventral root postvibration reflexes from triceps surae varied in magnitude but were usually depressed or abolished at 1.0 to 1.2 times the electrical reflex threshold. These responses returned to previbration control amplitudes within 20 to 35 min. Magnitude of depression and time to recovery were dependent on the intensity of the electrical stimulus. In five experiments, depression of postvibration reflex activity and recovery were accompanied by gradual recovery in amplitude of the group I volley to previbration amplitudes. Elevated group Ia axonal electrical thresholds, monitored from seven isolated units, were observed to recover to previbration values in parallel with postvibration reflex recovery to control amplitudes. At electrical stimulus intensities greater than 1.4 times the reflex threshold, postvibration reflex responses were often potentiated, probably reflecting posttetanic potentiation of group Ia pathways activated at their higher axonal thresholds. In two observations, postvibration Ib axonal electrical thresholds did not change. Overall, the findings supported the proposal that postvibration depression of soleus H-reflexes in humans or cats is caused by both disfacilitation and autogenetic inhibition due to withdrawal of Ia afferent activation and increased selectivity of Ib afferent fiber stimulation, respectively.     

Spatial facilitation of motor evoked responses in monitoring during spinal surgery.

During spinal cord monitoring, motor responses in the tibialis anterior muscles were recorded on transcranial electrical stimulation of the motor cortex. In order to facilitate the responses, the cortical stimulus was preceded by a train of stimuli to the foot sole within the receptive field of the withdrawal reflex of the tibialis anterior muscle. This cutaneous input provides a spatial facilitation of the cortically elicited response. When the stimulus interval was 50-100 ms, large and reliable responses were seen in most cases.     

Reproducibility of tendon jerk reflexes during a voluntary contraction.

OBJECTIVES: The present study explored whether testing tendon jerks during voluntary contraction of the test muscle would improve reproducibility by effectively 'clamping' the excitability of the motoneurone pool at firing threshold. METHODS: Tendon jerk reflexes of soleus, tibialis anterior and vastus lateralis and the soleus H reflex were recorded in 12 healthy subjects at rest and during voluntary contractions of 10-20% of maximum. Recordings were repeated 8-10 times in 5 subjects, in whom reflex symmetry was also determined. RESULTS: Not all tendon jerk reflexes could be recorded at rest, and the variability of latency and amplitude was high. All reflexes could be recorded in each subject during contractions. The latency of tendon jerk reflexes decreased by approximately 2 ms during contractions, but H-reflex latency decreased by only 0.2-0.3 ms. For the tendon jerks, an asymmetry of >3.0 ms at rest and >2.5 ms contracting would be outside 3 SD of the normal mean. In repeat studies, the coefficient of variation of reflex latency was <4% for the tendon jerk. CONCLUSIONS: A voluntary contraction could potentiate the tendon jerk by a number of mechanisms, but the most important is probably enhancement of the excitability of the motoneurone pool. The present techniques should increase the value of tendon reflex testing when assessing possible peripheral nerve, plexus and root disturbances.     

Definition of human reflex excitability by statistical analysis of quantal EMG responses

A precise method has been devised to estimate soleus motoneurone pool excitability by probit analysis of quantal (all-or-none) reflex EMG responses to critical electrical stimulation. The technique is shown to be sensitive to changes induced by weak excitatory or inhibitory inputs and is likely to be useful in the study of monosynaptic proprioceptive reflexes.     

Posterior root-muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord

Continuous epidural stimulation of lumbar posterior root afferents can modify the activity of lumbar cord networks and motoneurons, resulting in suppression of spasticity or elicitation of locomotor-like movements in spinal cord-injured people. The aim of the present study was to demonstrate that posterior root afferents can also be depolarized by transcutaneous stimulation with moderate stimulus intensities. In healthy subjects, single stimuli applied through surface electrodes placed over the T11-T12 vertebrae with a mean intensity of 28.6 V elicited simultaneous, bilateral monosynaptic reflexes in quadriceps, hamstrings, tibialis anterior, and triceps surae by depolarization of lumbosacral posterior root fibers. The nature of these posterior root-muscle reflexes was demonstrated by the duration of the refractory period, and by modifying the responses with vibration and active and passive movements. Stimulation over the L4-L5 vertebrae selectively depolarized posterior root fibers or additionally activated anterior root fibers within the cauda equina depending on stimulus intensity. Transcutaneous posterior root stimulation with single pulses allows neurophysiological studies of state- and task-dependent modulations of monosynaptic reflexes at multiple segmental levels. Continuous transcutaneous posterior root stimulation represents a novel, non-invasive, neuromodulative approach for individuals with different neurological disorders.     

Tetanus toxin reduces local and descending regulation of the H‐reflex

Introduction: Skeletal muscles that are under the influence of tetanus toxin show an exaggerated reflex response to stretch. We examined which changes in the stretch reflex may underlie the exaggerated response. Methods: H‐reflexes were obtained from the tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles in rats 7 days after intramuscular injection of tetanus toxin into the TA. Results: We found effects of the toxin on the threshold, amplitude, and duration of H‐waves from the TA. The toxin inhibited rate‐dependent depression in the FDB between the stimulation frequencies of 0.5–50 HZ and when a conditioning magnetic stimulus applied to the brain preceded a test electrical stimulus delivered to the plantar nerve. Conclusions: Tetanus toxin increased the amplitude of the H‐wave and reduced the normal depression of H‐wave amplitude that is associated with closely timed stimuli, two phenomena that could contribute to hyperactivity of the stretch reflex. Muscle Nerve 49:495–501, 2014     

Cutaneous withdrawal reflexes of the upper extremity

We characterized reflexes of the upper limb elicited by electrical stimulation of the fingers. Surface electromyogram (EMG) was recorded from several upper extremity muscles, and a finger was stimulated through paired ring electrodes. A train of 4–10 shocks at a frequency of 300 Hz and an intensity 4–6 times the perceptual threshold was the most effective stimulus for evoking EMG activity in relaxed arm muscles. Habituation was prominent. Latencies of EMG activity were <100 ms for most proximal and forearm muscles, and at least 40 ms prior to voluntary withdrawal movements. The timing of EMG activity in arm muscles was similar to that of the E2 component of the cutaneomuscular reflex evoked in these same muscles during contraction, and coincided with a silent period in active hand muscles. We conclude that cutaneous stimuli to the fingers activate a complex motor pattern that tends to withdraw the hand at the same time the grasp is released. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:591–598, 1998.