Are changes in nociceptive withdrawal reflex magnitude a viable central sensitization proxy? Implications of a replication attempt.

OBJECTIVE: The nociceptive withdrawal reflex (NWR) has been proposed to read-out central sensitization (CS). Replicating a published study, it was assessed if the NWR magnitude reflects sensitization by painful heat. Additionally, NWR response rates were compared for two stimulation, the sural nerve at the lateral malleolus (SU) and the medial plantar nerve on the foot sole (MP), and three recording sites, biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA) muscles. METHODS: 16 subjects underwent one experiment with six blocks of eight transcutaneous electrical stimulations to elicit the NWR while surface electromyography was collected. Tonic heat was concurrently applied in the same dermatome. Temperatures rose from 32 °C in the first to 46 °C in the last block following the previously published protocol. RESULTS: Tonic heat did not influence NWR magnitude. The highest NWR response rate was obtained for MP-TA combination (79%). Regarding elicitation in all three muscles, SU stimulation outperformed MP (59% vs 57%). CONCLUSIONS: The replication failed. NWR magnitude as a CS proxy in healthy subjects needs continued investigation. With respect to response rates, MP-TA proved efficient, whereas SU stimulation seemed preferable for multiple muscle recordings. SIGNIFICANCE: Unclear methodological descriptions in the original study affected CS and NWR replication. The NWR magnitude changes induced by CS may closely depend on the different stimulation methods used.

Improved acquisition of contact heat evoked potentials with increased heating ramp.

Contact heat evoked potentials (CHEPs) represent an objective and non-invasive measure to investigate the integrity of the nociceptive neuraxis. The clinical value of CHEPs is mostly reflected in improved diagnosis of peripheral neuropathies and spinal lesions. One of the limitations of conventional contact heat stimulation is the relatively slow heating ramp (70 °C/s). This is thought to create a problem of desynchronized evoked responses in the brain, particularly after stimulation in the feet. Recent technological advancements allow for an increased heating ramp of contact heat stimulation, however, to what extent these improve the acquisition of evoked potentials is still unknown. In the current study, 30 healthy subjects were stimulated with contact heat at the hand and foot with four different heating ramps (i.e., 150 °C/s, 200 °C/s, 250 °C/s, and 300 °C/s) to a peak temperature of 60 °C. We examined changes in amplitude, latency, and signal-to-noise ratio (SNR) of the vertex (N2-P2) waveforms. Faster heating ramps decreased CHEP latency for hand and foot stimulation (hand: F = 18.41, p < 0.001; foot: F = 4.19, p = 0.009). Following stimulation of the foot only, faster heating ramps increased SNR (F = 3.32, p = 0.024) and N2 amplitude (F = 4.38, p = 0.007). Our findings suggest that clinical applications of CHEPs should consider adopting faster heating ramps up to 250 °C/s. The improved acquisition of CHEPs might consequently reduce false negative results in clinical cohorts. From a physiological perspective, our results demonstrate the importance of peripherally synchronizing afferents recruitment to satisfactorily acquire CHEPs.

Normative data of contact heat evoked potentials from the lower extremities.

Contact heat evoked potentials (CHEPs) have become an acknowledged research tool in the assessment of the integrity of the nociceptive system and gained importance in the diagnostic work-up of patients with suspected small fiber neuropathy. For the latter, normative values for CHEP amplitude and latency are indispensable for a clinically meaningful interpretation of the results gathered in patients. To this end, CHEPs were recorded in 100 healthy subjects over a wide age range (20-80 years) and from three different dermatomes of the lower extremities (L2, L5, and S2). A normal baseline (35-52 °C) and increased baseline stimulation (42-52 °C) were applied. Statistical analysis revealed significant effects of stimulation site, stimulation intensity, and sex on CHEP parameters (N2 latency, N2P2 amplitude, and NRS). Significant positive correlations of body height with N2 latency, and pain ratings with N2P2 amplitudes were observed. This is the first time that normative values have been obtained from multiple dermatomes of the lower extremities. The present dataset will facilitate the clinical application of CHEPs in the neurophysiological diagnosis of small fiber neuropathy and by discerning pathological findings help establish a proximal-distal gradient of nerve degeneration in polyneuropathies.

Contact heat evoked potentials: Reliable acquisition from lower extremities.

OBJECTIVE: To investigate test-retest reliability of contact heat evoked potentials (CHEPs) from lower extremities using two different stimulation protocols, i.e., normal and increased baseline temperature. METHODS: A total of 32 able-bodied subjects were included and a subset (N = 22) was retested. CHEPs were recorded from three different dermatomes of the lower extremity (i.e., L2, L5, and S2). Test-retest reliability of CHEPs acquisition after simulation in various lower limb dermatomes using different stimulation protocols was analyzed. RESULTS: The study revealed an improved acquisition of CHEPS employing the increased baseline protocol, particularly when stimulating more distal sites, i.e., dermatome L5 and S2. Based on repeatability coefficients, CHEP latency (N2 potential) emerged as the most robust CHEP parameter. Although CHEP amplitudes (N2P2 complex) and pain ratings were decreased in the retest, amplitudes still showed fair to excellent intraclass correlation coefficients using normal baseline or increased baseline temperature, respectively. CONCLUSIONS: This is the first study to demonstrate that CHEPs acquisition from the lower extremities is improved by increasing the baseline temperature of the thermode. SIGNIFICANCE: This study highlights the usability of CHEPs as a viable diagnostic method to study small fiber integrity.

Cardiovascular control, autonomic function, and elite endurance performance in spinal cord injury.

We aimed to determine the relationship between level of injury, completeness of injury, resting as well as exercise hemodynamics, and endurance performance in athletes with spinal cord injury (SCI). Twenty-three elite male paracycling athletes (C3-T8) were assessed for neurological level/completeness of injury, autonomic completeness of injury, resting cardiovascular function, and time to complete a 17.3-km World Championship time-trial test. A subset were also fitted with heart rate (HR) monitors and their cycles were fitted with a global positioning systems device (n = 15). Thoracic SCI exhibited higher seated systolic blood pressure along with superior time-trial performance compared with cervical SCI (all P < 0.01). When further stratified by autonomic completeness of injury, the four athletes with cervical autonomic incomplete SCI exhibited a faster time-trial time and a higher average speed compared with cervical autonomic complete SCI (all P < 0.042). Maximum and average HR also tended to be higher in cervical autonomic incomplete vs autonomic complete. There were no differences in time-trial time, HR, or speed between thoracic autonomic complete vs incomplete SCI. In conclusion, autonomic completeness of injury and the consequent ability of the cardiovascular system to respond to exercise appear to be a critical determinant of endurance performance in elite athletes with cervical SCI.

Applanation tonometry: a reliable technique to assess aortic pulse wave velocity in spinal cord injury.

STUDY DESIGN: Within-subject repeated measures. OBJECTIVES: To determine the intra- and inter-tester reliability of aortic pulse wave velocity (aPWV) measurements collected using applanation tonometry in individuals with spinal cord injury (SCI). SETTING: Inpatient Rehabilitation Centre and outpatient Clinic in Vancouver, BC, Canada. METHODS: Fifteen men and three women with traumatic SCI (age: 46±16 years; C3-L1; American Spinal Injury Association Impairment Scale A-D; 2-284 months post injury) participated in two testing sessions separated by an average of 2 days. During each testing session, aPWV measurements were collected in the supine position following 10 min of rest. Arterial blood pressure waveforms were collected simultaneously by two trained raters at the carotid and femoral arterial sites using applanation tonometry. Heart rate was continuously measured using a single-lead electrocardiogram, whereas brachial blood pressures were measured at 5-min intervals using an automated device. RESULTS: Intra- and inter-tester aPWV measurements demonstrated almost perfect reliability with intraclass correlation coefficients of 0.91 and 0.98 (P<0.001), and coefficients of variation of 5.9% and 3.4%, respectively. The smallest detectable differences (SDDs) for intra- and inter-tester measurements were 0.9 m s(-1) and 0.6 m s(-1), respectively. There were no significant differences in heart rate or blood pressure between intra- and inter-testing sessions. CONCLUSION: Applanation tonometry measurements of aPWV are reliable in individuals with SCI. In addition, the SDDs were smaller than a clinically relevant value, suggesting that this measurement is suitable for repeated measures study designs in SCI.

Modulation of spinal neuronal excitability by spinal direct currents and locomotion after spinal cord injury.

OBJECTIVE: Spinal neuronal function is impaired after a severe spinal cord injury (SCI) and can be assessed by the analysis of spinal reflex (SR) behavior. We applied transcutaneous spinal direct current stimulation (tsDCS) and locomotor activity, to determine whether the excitability of spinal neuronal circuitries underlying locomotion can be modulated after motor complete SCI. METHOD: SRs were evoked by non-noxious electrical stimulation of the tibial nerve. SR behavior was assessed before, immediately after, and 20 min after four different interventions (anodal, cathodal, sham tsDCS, or locomotion) in subjects with motor complete SCI and healthy subjects. RESULTS: SR amplitudes in SCI subjects were increased after anodal tsDCS by 84% (p < 0.05). Cathodal, sham tsDCS and locomotion had no influence on SR amplitudes. In addition, reflex threshold was lower after anodal tsDCS and locomotion in SCI subjects (p < 0.05). CONCLUSION: Anodal tsDCS is able to modulate spinal neuronal circuitries after SCI. SIGNIFICANCE: This novel, noninvasive approach might be used as a tool to excite spinal neuronal circuitries. If applied repetitively within a training approach, anodal tsDCS might prevent adverse alterations in spinal reflex function in severely affected SCI subjects, i.e., a manifestation of a spinal neuronal dysfunction taking part below the level of a spinal lesion.

Influence of spinal reflexes on the locomotor pattern after spinal cord injury.

In complete spinal cord injured (cSCI) subjects a shift from dominant early (60-120ms latency) to dominant late (120-450ms latency) spinal reflex (SR) components occurs over time after injury. This shift is assumed to reflect a spinal neuronal dysfunction below the level of a spinal lesion. The neuronal pathways of SR are suggested to be closely connected with spinal locomotor circuits. The aim of this study was to explore the influence of the two SR components on the electromyographic (EMG) pattern induced by assisted locomotion in cSCI subjects. Leg muscle EMG activity was analysed during assisted locomotion in both healthy and motor cSCI subjects. SR were evoked by non-noxious tibial nerve stimulation during mid-stance phase of the gait cycle. Early and late SR components had a differential influence on the locomotor pattern. In healthy and cSCI subjects with a dominant early SR component the locomotor EMG pattern was modulated in the form of a short increase in leg flexors activity in the stance phase (tibialis anterior, biceps femoris). In contrast, in chronic cSCI subjects with a dominant late SR component no activation in biceps femoris but a long-lasting activation of tibialis anterior and rectus femoris muscles during the stance phase was evoked. It is concluded that the same tibial nerve stimuli activated two different neuronal pathways, resulting in divergent interactions with spinal locomotor circuitries. It is proposed that the two SR components have different physiological roles during locomotion.

Neuronal dysfunction in chronic spinal cord injury.

This review describes the changes of spinal neuronal function that occur after a motor complete spinal cord injury (cSCI) in humans. In healthy subjects, polysynaptic spinal reflex (SR) evoked by non-noxious tibial nerve stimulation consists of an early SR component and rarely a late SR component. Soon after a cSCI, SR and locomotor activity are absent. After spinal shock; however, an early SR component re-appears associated with the recovery of locomotor activity in response to appropriate peripheral afferent input. Clinical signs of spasticity take place in the following months, largely as a result of non-neuronal changes. After around 1 year, the locomotor and SR activity undergo fundamental changes, that is, the electromyographic amplitude in the leg muscles during assisted locomotion exhaust rapidly, accompanied by a shift from early to dominant late SR components. The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete spinal cord injury (SCI). At about 1 year after injury, in most cSCI subjects the neuronal dysfunction is fully established and remains more or less stable in the following years. It is assumed that in chronic SCI, the patient's immobility resulting in a reduced input from supraspinal and peripheral sources leads to a predominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and SR generation. Training of spinal interneuronal circuits including the enhancement of an appropriate afferent input might serve as an intervention to prevent neuronal dysfunction after an SCI.

Changes in spinal reflex and locomotor activity after a complete spinal cord injury: a common mechanism?

Locomotor activity and spinal reflexes (SRs) show common features in different mammals, including humans. Here we report the time-course of the development of locomotor activity and SRs after a complete spinal cord injury in humans. SRs evoked by tibial nerve stimulation were studied, as was the leg muscle electromyography activity evoked by mechanically assisted locomotion (Lokomat) in biceps femoris, rectus femoris, tibialis anterior and gastrocenmius medialis. Around 8 weeks after the injury, an early SR component (latency 60-120 ms) appeared, as in healthy subjects, and a well-organized leg muscle activity was present during assisted locomotion. At around 6 months after injury an additional, late reflex component (latency 120-450 ms) appeared, which remained even 15 years after the spinal cord injury. In contrast, the early component had markedly decreased at 18 months after injury. These changes in SR were associated with a loss of electromyography activity and a successively stronger electromyography exhaustion (i.e. decline of electromyography amplitude), when comparing the level of electromyography activity at 2 and 10 min, respectively, during assisted locomotion. These changes in electromyography activity affected mainly the biceps femoris, gastrocenmius medialis and tibialis anterior but less so the rectus femoris. When the amplitude relationship of the early to late SR component was calculated, there was a temporal relationship between the decrease of the early component and an increase of the late component and the degree of exhaustion of locomotor activity. In chronic, severely affected but sensori-motor incomplete spinal cord injury subjects a late SR component, associated with an electromyography exhaustion, was present in subjects who did not regularly perform stepping movements. Our data are consistent with the proposal of a common mechanism underlying the changes in SR activity and locomotor activity after spinal cord injury. These findings should be taken into consideration in the development of novel rehabilitation schemes and programs to facilitate regeneration-inducing therapies in spinal cord injury subjects.