Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system

Animal experiments have shown that the nociceptive reflex can be used as an indicator of central temporal integration in the nociceptive system. The aim of the present study on humans was to investigate whether the nociceptive reflex, evoked by repetitive strong electrical sural nerve stimuli, increased when summation was reported by the volunteers. The reflexes were recorded from the biceps femoris and rectus femoris muscles in eight volunteers following a series of stimulations at 0.1, 1, 2, and 3 Hz. Each series consisted of five consecutive stimuli. Using 0.1- and 1-Hz stimulation, the reflex was not facilitated in the course of the five consecutive stimuli. Following 2- and 3-Hz stimulation, the reflex size (root mean square amplitude) increased significantly during the course of the fifth stimulus. This reflex facilitation was followed by a significant increase (summation) in the pain magnitude when compared with 1- and 0.1-Hz stimulation. Furthermore, the threshold for psychophysical summation could be determined. This threshold (stimulus intensity) decreased when the stimulus frequency (1–5 Hz) of the five consecutive stimuli was increased. The nociceptive reflex and the psychophysical summation threshold might be used to clarify and quantify aspects of temporal summation within the human nociceptive system.     

Short and medium latency muscle responses evoked by electrical vestibular stimulation are a composite of all stimulus frequencies

Electrical vestibular stimulation produces biphasic responses in muscles maintaining balance. The two components of these muscle responses (termed the short latency and medium latency components) are believed to be independent and elicited by vestibular stimuli of different frequencies. We tested these hypotheses by determining (a) if frequency-specific stimulation protocols could evoke independently the short and medium latency responses and (b) whether these two components are triggered by distinct brain regions with a fixed time delay, interacting around 10 Hz. First, subjects were provided 10–25 Hz, 0–10 Hz, and 0–25 Hz vestibular stimuli to selectively modulate the short latency, medium latency, or both components of the response; and second, they were provided twenty sinusoidal stimuli from 1 to 20 Hz with a 0–20 Hz control trial, designed to determine whether an interaction between the short and medium latency responses occurs at a specific stimulation frequency. Both the 0–10 Hz and 10–25 Hz vestibular stimuli elicited multiphasic waveforms, suggesting the short and medium latency components were not modulated independently by the frequency-specific stimuli. Sinusoidal vestibular stimuli evoked responses at the stimulated frequency but no evidence of a reflex component interaction was observed. Instead, summation of the responses evoked by each of the sinusoidal stimuli resembled the biphasic response to broad bandwidth stimuli. Due to the lack of interaction and linear contribution of all stimulus frequencies to both the short and medium latency responses, the present results support the use of broad bandwidth electrical vestibular signal for physiological or clinical testing.     

Modulation of heat evoked nociceptive withdrawal reflexes by painful intramuscular conditioning stimulation

Convergence between cutaneous heat nociceptors and muscles afferents was investigated by applying a phasic, conditioning electrical stimulus to the tibialis anterior muscle (a train of five 1 ms pulses over 21 ms) at varying time intervals relative to a thermal test stimulus used for evoking the withdrawal reflex in humans. The 200 ms thermal stimulus was applied on the dorsum of the foot at an intensity of two times the pain threshold. The conditioning electrical stimulus was applied at an intensity of two times the pain threshold via a set of intramuscular needle electrodes. The conditioning-test interval was varied between –400 ms and 8,000 ms at 17 different intervals. The mean reflex onset latency of reflexes evoked by thermal stimuli alone was 354 ± 9 ms. A facilitation of the reflex was seen when the conditioning stimulus was applied 275 ms (174 ± 30% compared to control) and 300 ms (162 ± 32% compared to control) after the test stimulus onset indicating sensory convergence between muscle afferents (group I–III) and cutaneous Aδ heat nociceptors arriving simultaneously at the spinal cord.     

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10–25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50–60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.     

Eye movements during combined pursuit, optokinetic and vestibular stimulation in macaque monkey

 During natural behaviour in a visual environment, smooth pursuit eye movements (SP) usually override the vestibular-ocular reflex (VOR) and the optokinetic reflex (OKR), which stem from head-in-space and scene-relative-to-eye motion, respectively. We investigated the interaction of SP, VOR, and OKR, which is not fully understood to date. Eye movements were recorded in two macaque monkeys while applying various combinations of smooth eye pursuit, vestibular and optokinetic stimuli (sinusoidal horizontal rotations of visual target, chair and optokinetic pattern, respectively, at 0.025, 0.05, 0.1, 0.2, 0.4, and 0.8 Hz, corresponding to peak stimulus velocities of 1.25–40°/s for a standard stimulus of ±8°). Slow eye responses were analysed in terms of gain and phase. During SP at mid-frequencies, the eyes were almost perfectly on target (gain 0.98 at 0.1 Hz), independently of a concurrent vestibular or optokinetic stimulus. Pursuit gain at lower frequencies, although being almost ideal (0.98 at 0.025 Hz with pursuit-only stimulation), became modified by the optokinetic input (gain increase above unity when optokinetic stimulus had the same direction as target, decrease with opposite direction). At higher stimulus frequencies, pursuit gain decreased (down to 0.69 at 0.8 Hz), and the pursuit response became modified by vestibular input (gain increase during functionally synergistic combinations, decrease in antagonistic combinations).Thus, the pursuit system in monkey dominates during SP-OKR-VOR interaction, but it does so effectively only in the mid-frequency range. The results can be described in the form of a simple dynamic model in which it is assumed that the three systems interact by linear summation. In the model SP and OKR dominate VOR in the low- to mid-frequency/velocity range, because they represent closed loop systems with high internal gain values (>>1) at these frequencies/velocities, whereas the VOR represents an open loop system with about unity-gain (up to very high frequencies). SP dominance over OKR is obtained by allowing an ’attentional/volitional’ mechanism to boost SP gain and a predictive mechanism to improve its dynamics. Received: 27 November 1998 / Accepted: 8 March 1999     

Reaction time facilitation by acoustic task-irrelevant stimuli is not related to startle

Previous research has been interpreted to suggest that the startle reflex mediates the RT facilitation observed if intense, accessory acoustic stimuli are presented coinciding with the onset of a visual imperative stimulus in a forewarned simple RT task. The present research replicated this finding as well as the facilitation of startle observed during the imperative stimulus. It failed, however, to find any relationship between the size of the blink startle reflex elicited by the accessory acoustic stimuli, which differed in intensity and rise time, and RT or RT facilitation observed on trials with accessory acoustic stimuli. This finding suggests that the RT facilitation is not mediated by the startle reflex elicited by the accessory acoustic stimuli.     

Modulation of the soleus H reflex by electrical subcortical stimuli in humans

Over the past two decades, the H reflex has been used as a neural tool to assess the effect on the motoneuronal pool of conditioning volleys in supraspinal descending tracts elicited by transcranial magnetic stimulation (TMS) or auditory stimuli. However, mechanisms mediating such modulation are unclear. These hypothesized neural pathways are likely to be affected by single electrical stimulus applied through the electrodes implanted in the subthalamic nucleus for deep brain stimulation (sSTNDBS). To improve our knowledge on such mechanisms, we examined in 11 Parkinson’s disease patients the effects of conditioning sSTNDBS applied contralateral and ipsilateral to the H reflex recording on the amplitude of the soleus H reflex, at interstimulus intervals (ISIs) between 0 and 110 ms. There was a significant main effect of the ISI (P < 0.001) and of the sSTNDBS stimulation side (P = 0.019) on the percentage change in the soleus H-reflex amplitude. Contralateral sSTNDBS modulation of the soleus H reflex resembles that of TMS in healthy subjects with two facilitation phases (at 5–20 ms and at 60 ms), while after ipsilateral sSTNDBS, there is only a single facilitation phase peaking up at 5 ms later than the first facilitation period observed with contralateral stimulation. These findings contribute to the discussion of the mechanisms underlying the excitability of the spinal alpha motoneuron pool and the modulation of the H reflex by supraspinal stimuli.     

Enhanced temporal summation of pressure pain in the trapezius muscle after delayed onset muscle soreness

Temporal summation of muscle pain is an important factor in musculoskeletal pain as central integration of repetitive nociceptive input can be facilitated in musculoskeletal pain patients. The aim of this study is to evaluate changes in temporal summation of pressure pain after induction of delayed onset muscle soreness (DOMS) of the trapezius muscle. Sixteen healthy volunteers participated in the study. Temporal summation of pain was induced by sequential pressure stimulation by a computer-controlled algometer. Sequential stimulation consisting of ten stimuli (at pressure pain threshold intensity) was applied over the trapezius muscle. Stimulus duration was 1 s and inter-stimulus intervals (ISI) were 1, 5, 10, and 30 s, respectively. The pain was rated on a continuous visual analogue scale (VAS, 10 cm) after each stimulus and normalised to the VAS score from the first stimulus. DOMS was induced in the right trapezius muscle by eccentric shoulder exercises while the left trapezius muscle served as control. Temporal summation of pressure evoked pain was measured before and 24 h after the exercise. At 24 h after exercise, soreness intensity during shoulder elevation was 3.7±0.2 cm, while no soreness was observed on the control side. When sequential pressure stimulation was applied to the DOMS muscle, VAS scores for 1 s ISI progressively increased to a higher level than before exercise (VAS increase for the last stimulus: 0.8±0.2 cm vs. 0.6±0.1 cm, P<0.05), while VAS scores for ISI 5, 10, and 30 s were not increased. On the control side, significant increases in VAS scores was observed for all ISIs but not affected by contralateral DOMS. Facilitation of temporal summation for 1 s ISI indicated that DOMS may increase the central excitability besides involving peripheral sensitisation. During DOMS there was no potential for further nociceptor sensitisation by repeated noxious pressure stimuli, which may account for the diminishment of temporal summation evoked by pressure stimuli with ISI 5, 10, and 30 s. These data indicate that muscle soreness might facilitate the central components of temporal summation to mechanical stimulation.     

Facilitation of the human nociceptive reflex by stimulation of Aβ-fibres in a secondary hyperalgesic area sustained by nociceptive input from the primary hyperalgesic area

Hyperalgesia was induced in healthy volunteers by topical capsaicin applied on the dorsum of the foot within the receptive field of the sural nerve. Under presence of hyperalgesia different normally non-noxious conditioning stimuli were applied to the hyperalgesic area and the polysynaptic nociceptive spinal reflex and pain ratings were used to assess central excitability. The nociceptive reflex was measured in the knee extensor and flexor muscles evoked by electrical stimulation of the sural nerve trunk at an intensity of 1.5 times the initial reflex threshold (an intensity above the pain threshold). Thermal stimulation of the primary hyperalgesic area (re)established both on-going spontaneous pain and secondary hyperalgesia. Thus, increased nociceptive reflexes were recorded and increased pain intensity reported when Aβ-fibres in the secondary hyperalgesic area were activated concurrently with the reflex testing after a non-noxious thermal stimulation of the primary hyperalgesic area. The Aβ-fibre activation was achieved by continuous low-intensity electrical stimulation (40 Hz) that was initiated after on-going pain produced by the thermal stimulation had waned. The same measurement without prior thermal conditioning stimulation of the primary area resulted in no reflex facilitation, indicating rapid changes in the central excitability with existence of on-going nociceptive activity. This indicates that the development and maintenance of secondary hyperalgesia are dependent on sustained peripheral nociceptive activity. The study also shows that a central summation of nociceptive and non-nociceptive afferent activity can occur once secondary hyperalgesia is present.     

Influence of different properties of a reaction time task on the pre-movement gating of input from Ia afferents to motoneurons

Summary The monosynaptic reflex (H reflex) is facilitated before movement onset in human subjects who are performing a conditioned plantar flexion of the ankle in a reaction time task. The aim of this study was to investigate how tightly this gating of Ia spindle input is coupled with the conditioned muscle contraction. Test H reflexes were elicited at various times during the reaction time (RT) in order to test the efficacy of Ia volleys on the soleus motoneurons. Tactile, auditory and visual go stimuli were used. The RT to a tactile stimulus was about the same as the RT to an auditory stimulus although distance and therefore conduction time from the site of stimulation to the cerebral cortex was much larger for the tactile than for the auditory modality. The RT to visual stimulation was about 20 ms longer than to the other two modalities. Although central latencies depended clearly on the stimulus modality the duration of the H reflex facilitation, i.e. the interval between the onset of the facilitation and the onset of the voluntary muscle contraction, was always the same. Similarly, the reflex facilitation was insensitive to the succeeding contrast of a visual go stimulus. The subjects were also examined in visual RT tasks in which different advance information about the laterality and the execution of the contraction was given. By combination the following four RT situations were realized: (1) simple, go, (2) choice, go, (3) simple, go — no go and (4) choice, go — no go. RT was shortest in the simple go and increased by about 65 ms in the choice, go and the simple, go — no go situation. It lengthened, however, less than 130 ms in the choice, go — no go situation indicating an interaction between the factors laterality and execution of the contraction. As with various stimulus modalities and succeeding contrasts, the premovement H reflex facilitation remained constant irrespective of the complexity of the RT task. This property was however not observed if data obtained within one RT task (constant modality, simple, go) were processed. There was a highly significant positive correlation between the duration of the facilitation and RT. The duration of the EMG burst of the conditioned contraction was, however, independent of RT. These results were interpreted as indicating that RT depended on attention which affects most central components of RT and that the interval between the onset of the gating process and the onset of the contraction (duration of the H reflex facilitation) might depend on several supraspinal motor centers whereas the duration of the EMG burst might be computed locally. Several studies including the present one provide a possible explanation for the lag between the onset of the H reflex facilitation and the movement onset. The relatively slow speed at which presynaptic inhibition at Ia afferents can be removed necessitates an early onset such that a fully operative spinal reflex for assistance of muscle contractions and correction of perturbances is assured at movement onset.     

Facilitation of female reproductive behavior from mesensephalic central gray in the rat.

Electrical stimulation in the mesencephalic central gray (CG) and adjacent subtectum through chronically implanted electrodes in free-moving estrogen-primed ovariectomized female rats elicited a rapid and large facilitation of the lordosis reflex in response to either male mounts or manula cutaneous stimuli. Unilateral stimulation was sufficient for this effect. The facilitation increased in a graded manner to increased stimulus intensity, and was optimally evoked by stimuli delivered at 50--150 Hz. Facilitation disappeared rapidly following the end ot electrical stimulation, and within 15 min, reflex performance returned to the prestimulation level. Lordosis facilitation appeared when no aversive responses occurred; stimulation with comparable parameters at the lateral edge of CG or in the mesencephalic reticular formation often resulted in postural changes or aversive responses but was not able to facilitate lordosis. Lordosis refelx facilitation was probably mediated by projections descending from neurons in and around the CG, and represents stimulation of a functional link between ascending somatosensory and descending motor systems for the control of lordosis behavior.     

Spinal substance P and N-methyl-D-aspartate receptors are coactivated in the induction of central sensitization of the nociceptive flexor reflex.

We have studied the effects and interactions of the neurokinin-1 receptor antagonist CP-96,345 and the N-methyl-D-aspartate receptor/channel blocker MK-801, both applied intravenously, on the flexor reflex and on the facilitation of the flexor reflex by conditioning stimulation of cutaneous C-afferents in decerebrate, spinalized, unanesthetized rats. The flexor reflex was evoked by subcutaneous electrical stimuli applied to the sural nerve innervation area 1/min at an intensity that activated C-fibers and was recorded as electromyogram from the ipsilateral hamstring muscles. The magnitude of the baseline flexor reflex was usually highly stable in the course of the experiments without experimental manipulations. The same stimulus was used as a conditioning train (0.9 Hz, 20 shocks) and caused a brief facilitation of the flexor reflex, which was maximal 0.5 and 1 min after stimulation (255.1 +/- 23.6% over baseline). During the course of the conditioning stimulus train, the reflex magnitude was gradually increased (wind-up). MK-801 (0.1 and 0.5 mg/kg) consistently depressed the polysynaptic flexor reflex. At a dose of 0.5 mg/kg, but not 0.1 mg/kg, MK-801 reduced the wind-up and blocked the facilitation of the flexor reflex induced by the conditioning stimulus by 90%. The facilitatory effect of 7 pmol intrathecal substance P was also partially reduced by MK-801. CP 96,345 (1 and 3 mg/kg) did not depress the flexor reflex, but dose-dependently antagonized reflex facilitation by the conditioning stimulus train, similarly to its antagonism of intrathecally applied 7 pmol substance P-induced facilitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The brief and the prolonged facilitatory effects of unmyelinated afferent input on the rat spinal cord are independently influenced by peripheral nerve section

Single C-fibre strength stimuli applied to the sciatic nerve in the decerebrate spinal rat evoke three separate bursts of activity in posterior biceps/semitendinosus flexor alpha motorneurones which are associated with the arrival in the spinal cord of volleys in the A-beta, A-delta and C-afferent fibres. Repetitive stimulation of the sciatic nerve at 1 Hz for 20 s generates a progressive wind-up of response and an after-discharge lasting up to 10 s. Twelve to fourteen days after section of the sciatic nerve, stimuli applied central to the section evoke a larger than normal response in the posterior biceps/semitendinosus flexor motorneurones and repetitive stimulation (1 Hz, 20 s) produces an after-discharge which is four times longer than that produced by stimulation of the intact nerve. In addition to the direct excitatory effects of sciatic nerve stimulation on the flexor motorneurones which lasts for seconds, conditioning stimuli to the sciatic nerve at C-fibre strength (1 Hz, 20 s) produce a facilitation of the flexor reflex evoked by a standard pressure stimulus to the ipsilateral and contralateral toes which lasts for 70 min. However, although the direct excitatory effects of stimulating a sectioned sciatic nerve on the posterior biceps/semitendinosus flexor motorneurones are exaggerated, the facilitation of the cutaneous flexion reflex evoked by stimulating sectioned sciatic nerves (1 Hz, 20 s) only lasts for 17 min. These results show that the mechanism which produces the rapid effects of sciatic nerve stimulation on the flexor reflex circuit can be separated from the mechanism which produces the prolonged facilitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamics of the horizontal vestibuloocular reflex after unilateral labyrinthectomy: response to high frequency, high acceleration, and high velocity rotations

Loss of vestibular information from one labyrinth results in a marked asymmetry in the horizontal vestibuloocular reflex (VOR). The results of prior studies suggest that long-term deficits in VOR are more severe in response to rapid impulses than to sinusoidal head movements. The goal of the present study was to investigate the VOR following unilateral labyrinthectomy in response to different stimuli covering the full range of physiologically relevant head movements in macaque monkeys. The VOR was studied 1–39 days post-lesion using transient head perturbations (up to 12,000°/s²), rapid rotations (up to 500°/s), and sinusoidal rotations (up to 15 Hz). In response to rotations with high acceleration or velocity, both contra- and ipsilesional gains remained subnormal. VOR gains decreased as a function of increasing stimulus acceleration or velocity, reaching minimal values of 0.7–0.8 and 0.3–0.4 for contra and ipsilesional rotations, respectively. For sinusoidal rotations with low frequencies and velocities, responses to contralesional stimulation recovered within ∼ 4 days. With increasing velocities and frequencies of rotation, however, the gains of contra- and ipsilesional responses remained subnormal. For each of the most challenging stimuli tested (i.e., 12,000°/s² transient head perturbations, 500°/s fast whole-body rotations and 15 Hz stimulation) no significant compensation was observed in contra- or ipsilesional responses over time. Moreover, we found that gain of the cervico-ocular reflex (COR) remained negligible following unilateral loss indicating that neck reflexes did not contribute to the observed compensation. VOR responses elicited by both sinusoidal and transient rotations following unilateral labyrinthectomy could be described by the same mathematical model. We conclude that the compensated VOR has comparable response dynamics for impulses and sinusoidal head movements.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Evidence suggesting that a transcortical reflex pathway contributes to cutaneous reflexes in the tibialis anterior muscle during walking in man

Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of the tibialis anterior (TA) EMG-activity at a latency of 70–95 ms in the early and middle swing phase of human walking. The present study investigated the underlying mechanism for this facilitation. In those subjects in whom it was possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17 tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve (3 shocks, 3-ms interval, 2.0–2.5× perception threshold) was found to have the same latency in the swing phase of walking. The facilitation observed during tonic dorsiflexion has been suggested to be – at least partly – mediated by a transcortical pathway. To investigate whether a similar mechanism contributes to the facilitation observed during walking, magnetic stimulation of the motor cortex (1.2× motor threshold) was applied in the early swing phase at different intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were more facilitated by prior sural-nerve stimulation (conditioning-test intervals of 50–80 ms) than the algebraic sum of the control MEP and the cutaneous facilitation in the EMG when evoked separately. In four of these subjects, a tibialis anterior H-reflex could also be evoked during walking. In none of the subjects was an increase of the H-reflex similar to that for the MEP observed. In five experiments on four subjects, MEPs evoked by magnetic and electrical cortical stimulation were compared. In four of these experiments, only the magnetically induced MEPs were facilitated by prior stimulation of the sural nerve. We suggest that a transcortical pathway may also contribute to late cutaneous reflexes during walking. Received: 24 September 1997 / Accepted: 2 June 1998     

Long-interval intracortical inhibition in a human hand muscle

When two motor cortical stimuli are delivered with an interstimulus interval of 50–200 ms, the response (motor evoked potential; MEP) to the second stimulus is typically suppressed. This phenomenon is termed long-interval intracortical inhibition (LICI), although data from one subject suggest that facilitation is possible. Moreover, we recently showed that suppression can be mediated at a spinal level. We characterized LICI more fully by exploring a broad range of contraction strengths and test stimulus intensities. MEPs were evoked in first dorsal interosseous by transcranial magnetic stimulation over the motor cortex. Single test and paired (conditioning-test interval of 100 ms) stimuli at intensities of 100–160% resting motor threshold were delivered at rest or during brief contractions of 10, 25, or 100% maximal voluntary force. Inhibition or facilitation was quantified with the standard ratio in which conditioned MEPs were expressed as a percentage of unconditioned MEPs. Inhibition was greatest at weak–moderate contraction strengths and least at rest and during maximal efforts. Both at rest and during maximal efforts, MEPs evoked by strong stimuli were facilitated. In a subset of subjects, cervicomedullary stimulation was used to activate the corticospinal tract to identify possible spinal influences on changes to MEPs. Contraction strength and test stimulus intensity each had different effects on unconditioned and conditioned MEP size, and hence, LICI is highly dependent on both factors. Further, because motoneurons are facilitated during contraction but disfacilitated after a strong conditioning stimulus, the standard ratio of LICI is of questionable validity during voluntary contractions.     

Effects of flexor reflex afferent stimulation on the soleus H reflex in patients with a complete spinal cord lesion: evidence for presynaptic inhibition of Ia transmission

Summary The effects of electrically stimulating the Flexor Reflex Afferent (FRA) on the soleus H reflexes were investigated in 34 paraplegic patients having a clinically complete spinal cord lesion. Conditioning stimuli (5–50 mA) were applied to the ipsilateral or contralateral sural nerve. The conditioning-test interval ranged from 20 to 1000 ms. A late ipsilateral flexor reflex (EMG) was found in all patients. A late contralateral extension reflex was sporadically observed in only 3 patients. The excitability curves usually showed two phases of ipsilateral H reflex inhibition and contralateral H reflex facilitation, one between 50 and 130 ms and the other after over 200 ms. These intervals correspond to early and late flexion reflexes. With high intensity stimulation the early and late ipsilateral inhibition fused. An early low threshold ipsilateral facilitation occured in 9 patients. The contralateral late facilitation was followed by prolonged inhibition in 10 patients. Changes in presynaptic inhibition were assessed by measuring the heteronymous monosynaptic Ia facilitation from quadriceps to soleus. For methodological reasons, it was only possible to investigate the effect of contralateral conditioning volleys which was performed in 5 patients. A significant and regular reduction of the heteronymous Ia facilitation was found in 4 patients. This reduction is taken to indicate that the FRA evokes presynaptic inhibition of Ia transmission to alpha motoneurones. Presynaptic inhibition was also indicated by the enhancement of a vibratory stimulus induced inhibition in 2 subjects. These results are consistent with the hypothesis that the reflex organization in patients with a spinal cord section is similar to that of the acute spinal cat injected with DOPA.     

Startle blink facilitation during the go signal of a reaction time task is not affected by movement preparation or attention to the go signal

Startle reflex eliciting stimuli presented at the onset of the go signal in a simple forewarned reaction time (RT) task (at a SOA of 0 ms) elicit larger blink reflexes than do stimuli presented later (e.g., at a SOA of 150 ms) or during inter trial intervals. The present study investigated whether this facilitation is affected by attention to the go signal or motor preparation. Participants performed a forewarned reaction time task that crossed the requirements for a speeded response (Hold versus Move) and for a discrimination task performed with the go signal (Report versus No report). Relative to control reflexes, blinks elicited at a SOA of 0 ms were facilitated and blinks elicited at a SOA of 150 ms were inhibited. RTs were slower on trials that required attention to the go signal and in both attention conditions and at both SOAs shortened in the presence of a blink-eliciting stimulus. However, neither attention to the go signal nor motor preparation affected blink facilitation at the 0 ms SOA. This finding suggests that the blink reflex facilitation observed at a SOA of 0 ms with the onset of a go signal reflects on the summation of sub- and supra-threshold activations of the startle pathway.     

Standardizing procedures to study sensitization of human spinal nociceptive processes: Comparing parameters for temporal summation of the nociceptive flexion reflex (TS-NFR)

Temporal summation of pain (TS-pain) is the progressive increase in pain ratings during a series of noxious stimulations. TS-pain has been used to make inferences about sensitization of spinal nociceptive processes; however, pain report can be biased thereby leading to problems with this inference. Temporal summation of the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception) can potentially overcome report bias, but there have been few attempts (generally with small Ns) to standardize TS-NFR procedures. In this study, 50 healthy participants received 25 series of noxious electric stimulations to evoke TS-NFR and TS-pain. Goals were to: 1) determine the stimulation frequency that best elicits TS-NFR and reduces electromyogram (EMG) contamination from muscle tension, 2) determine the minimum number of stimulations per series before NFR summation asymptotes, 3) compare NFR definition intervals (90-150 ms vs. 70-150 ms post-stimulation), and 4) compare TS-pain and TS-NFR when different stimulation frequencies are used. Results indicated TS-NFR should be elicited by a series of three stimuli delivered at 2.0 Hz and TS-NFR should be defined from a 70-150 ms post-stimulation scoring interval. Unfortunately, EMG contamination from muscle tension was greatest during 2.0 Hz series. Discrepancies were noted between TS-NFR and TS-pain which raise concerns about using pain ratings to infer changes in spinal nociceptive processes. And finally, some individuals did not have reliable NFRs when the stimulation intensity was set at NFR threshold during TS-NFR testing; therefore, a higher intensity is needed. Implications of findings are discussed.     

Ultrastructure of a Sarcocystis sp. infecting skinks of the genus Agama

Macroscopically visible sarcocysts were observed in the skeletal muscles of naturally infected skinks of the genus Agama (infection rate 11.3%). Sarcocysts were described by means of transmission electron microscopy. These cysts measured 0.03–0.25 × 0.38–1.7 mm (mean 0.12 × 1.1 mm). Typical mature cysts were bordered by a primary cyst wall that measured 2.4–5.3 μm (mean 3.9 μm) and was folded into a few nonbranched finger-like protrusions measuring 0.7–1.5 × 1.0–2.5 μm (mean 1.2 × 1.5 μm). These protrusions contained granular elements, but filaments and tubular elements were not observed. A relatively thick, homogeneous tape was observed just underneath the primary cyst wall, measuring 0.5–1.0 μm (mean 0.8 μm) and containing a granulated ground substance in which filaments and tubular elements were not observed. Metrocytes measured 3.1–5.5 × 4.2–7.2 μm (mean 4.0 × 5.8 μm) and merozoites measured 1.2–3.3 × 4.4–8.6 μm (mean 2.6 × 7.5 μm). The fine ultrastructural characteristics of both metrocytes and merozoites were similar to those described for many Sarcocystis species and were generally nonspecific. Received: 21 February 2000 / Accepted: 1 March 2000