Cold pain hypersensitivity predicts trajectories of pain and disability after low back surgery: a prospective cohort study.

Improving the ability to predict persistent pain after spine surgery would allow identification of patients at risk and guide treatment decisions. Quantitative sensory tests (QST) are measures of altered pain processes, but in our previous study, preoperative QST did not predict pain and disability at single time-points. Trajectory analysis accounts for time-dependent patterns. We hypothesized that QST predict trajectories of pain and disability during 1 year after low back surgery. We performed a trajectory analysis on the cohort of our previous study (n = 141). Baseline QST included electrical, pressure, heat, and cold stimulation of the low back and lower extremity, temporal summation, and conditioned pain modulation. Pain intensity and Oswestry Disability Index were measured before, and 2, 6, and 12 months after surgery. Bivariate trajectories for pain and disability were computed using group-based trajectory models. Multivariable regressions were used to identify QST as predictors of trajectory groups, with sociodemographic, psychological, and clinical characteristics as covariates. Cold pain hypersensitivity at the leg, not being married, and long pain duration independently predicted worse recovery (complete-to-incomplete, incomplete-to-no recovery). Cold pain hypersensitivity increased the odds for worse recovery by 3.8 (95% confidence intervals 1.8-8.0, P < 0.001) and 3.0 (1.3-7.0, P = 0.012) in the univariable and multivariable analyses, respectively. Trajectory analysis, but not analysis at single time-points, identified cold pain hypersensitivity as strong predictor of worse recovery, supporting altered pain processes as predisposing factor for persisting pain and disability, and a broader use of trajectory analysis. Assessment of cold pain sensitivity may be a clinically applicable, prognostic test.

Intense and sustained pain reduces cortical responses to auditory stimuli: Implications for the interpretation of the effects of heterotopic noxious conditioning stimulation in humans.

Phasic pain stimuli are inhibited when they are applied concomitantly with a conditioning tonic stimulus at another body location (heterotopic noxious conditioning stimulation, HNCS). While the effects of HNCS are thought to rely on a spino-bulbo-spinal mechanism in animals (termed diffuse noxious inhibitory controls, DNIC), the underlying neurophysiology in humans may involve other pathways. In this study, we investigated the role of concomitant supraspinal mechanisms during HNCS by presenting auditory stimuli during a conditioning tonic painful stimulus (the cold pressor test, CPT). Considering that auditory stimuli are not conveyed through the spinal cord, any changes in brain responses to auditory stimuli during HNCS can be ascribed entirely to supraspinal mechanisms. Electroencephalography (EEG) was recorded during HNCS, and auditory stimuli were administered in three blocks, before, during and after HNCS. Nociceptive withdrawal reflexes (NWRs) were recorded at the same time points to investigate spinal processing. Our results showed that AEPs were significantly reduced during HNCS. Moreover, the amplitude of the NWR was significantly diminished during HNCS in most participants. Given that spinal and supraspinal mechanisms operate concomitantly during HNCS, the possibility of isolating their individual contributions in humans is questionable. We conclude that the net effects of HCNS are not independent from attentional/cognitive influences.

Can quantitative sensory tests predict failed back surgery?: A prospective cohort study.

BACKGROUND: Failed back surgery syndrome (FBSS) is a pain condition refractory to therapy, and is characterised by persistent low back pain after spinal surgery. FBSS is associated with severe disability, low quality of life and high unemployment. We are currently unable to identify patients who are at risk of developing FBSS. Patients with chronic low back pain may display signs of central hypersensitivity as assessed by quantitative sensory tests (QST). This can contribute to the risk of developing persistent pain after surgery. OBJECTIVE: We tested the hypothesis that central hypersensitivity as assessed by QST predicts FBSS. DESIGN: Prospective cohort study. SETTING: Three tertiary care centres. PATIENTS: 141 patients scheduled for up to three segment spinal surgery for chronic low back pain (defined as at least 3 on a numerical rating scale on most days during the week and with a minimum duration of 3 months) due to degenerative changes. OUTCOMES: We defined FBSS as persistent pain, persistent disability or a composite outcome defined as either persistent pain or disability. The primary outcome was persistent pain 12 months after surgery. We applied 14 QST using electrical, pressure and temperature stimulation to predict FBSS and assessed the association of QST with FBSS in multivariable analyses adjusted for sociodemographic, psychological and clinical and surgery-related characteristics. RESULTS: None of the investigated 14 QST predicted FBSS, with 95% confidence intervals of crude and adjusted associations of all QST including one as a measure of no association. Results remained robust in all sensitivity and secondary analyses. CONCLUSION: The study indicates that assessment of altered central pain processing using current QST is unlikely to identify patients at risk of FBSS and is therefore unlikely to inform clinical decisions.

A new experimental model of muscle pain in humans based on short-wave diathermy.

BACKGROUND: Experimental models of pain in humans are crucial for understanding pain mechanisms. The most often used muscle pain models involve the injection of algesic substances, such as hypertonic saline solution or nerve growth factor or the induction of delayed onset muscle soreness (DOMS) by an unaccustomed exercise routine. However, these models are either invasive or take substantial time to develop, and the elicited level of pain/soreness is difficult to control. To overcome these shortcomings, we propose to elicit muscle pain by a localized application of short-wave diathermy (SWD). METHODS: In this crossover study, SWD was administered to 18 healthy volunteers to the wrist extensor muscle group, with a constant stimulation intensity and up to 4 min. Pressure pain threshold (PPT), pinprick sensitivity (PPS) and self-reported muscle soreness were assessed at baseline and at 0, 30 and 60 min after application of SWD. RESULTS: SWD evoked localized muscle pain/soreness in the wrist extensor muscle group and a decrease of PPT in the treated arm compared with the control arm that lasted for at least 60 min, reflecting ongoing hyperalgesia after SWD application. PPS was not significantly altered 30-60 min following SWD, suggesting a minimal contribution from skin tissue to sustained hyperalgesia. CONCLUSIONS: SWD was able to elicit muscle soreness and hyperalgesia up to 60 min after its application. Thus, this new model represents a promising tool for investigating muscle pain in humans. SIGNIFICANCE: This study presents an experimental model to elicit sustained muscle pain based on short-wave diathermy. The main advantages of the model are its noninvasiveness, the possibility to control stimulation parameters in a reliable way and the convenience of the time frame in which pain and hyperalgesia are developed.

A Novel Stimulation Paradigm to Limit the Habituation of the Nociceptive Withdrawal Reflex.

In gait rehabilitation, combining gait therapy with functional electrical stimulation based on the nociceptive withdrawal reflex (NWR) improves walking velocity and gait symmetry of hemiparetic patients. However, habituation of the NWR can affect the efficacy of training. The current study aimed at identifying the stimulation parameters that would limit, in healthy participants, the habituation of the NWR. The NWR was elicited at every heel-off while the participants walked on a treadmill. Three stimulation paradigms were tested: deterministic paradigm (fixed parameters), stochastic pulse duration paradigm (varying the pulse duration of the stimuli), and stochastic frequency paradigm (varying the frequency of the stimuli). The charge delivered for the three paradigms was identical. The reflex response was quantified by the EMG activity of the tibialis anterior (TA) muscle and as ankle and hip joints angle changes. The ankle dorsiflexion and TA EMG responses were not significantly reduced with the stochastic pulse duration paradigm, in contrast to the two other paradigms. Hence, using a stochastic pulse duration stimulation paradigm seemed to be effective in limiting the habituation of the NWR in heathy individuals. This might be highly relevant for effective gait rehabilitation.

Design and test of an automated version of the modified Jebsen test of hand function using Microsoft Kinect.

BACKGROUND: The present paper describes the design and evaluation of an automated version of the Modified Jebsen Test of Hand Function (MJT) based on the Microsoft Kinect sensor. METHODS: The MJT was administered twice to 11 chronic stroke subjects with varying degrees of hand function deficits. The test times of the MJT were evaluated manually by a therapist using a stopwatch, and automatically using the Microsoft Kinect sensor. The ground truth times were assessed based on inspection of the video-recordings. The agreement between the methods was evaluated along with the test-retest performance. RESULTS: The results from Bland-Altman analysis showed better agreement between the ground truth times and the automatic MJT time evaluations compared to the agreement between the ground truth times and the times estimated by the therapist. The results from the test-retest performance showed that the subjects significantly improved their performance in several subtests of the MJT, indicating a practice effect. CONCLUSIONS: The results from the test showed that the Kinect can be used for automating the MJT.

Lateral inhibition during nociceptive processing.

Spatial summation of pain (SSP) is the increase of perceived intensity that occurs as the stimulated area increases. Spatial summation of pain is subadditive in that increasing the stimulus area produces a disproportionately small increase in the perceived intensity of pain. A possible explanation for subadditive summation may be that convergent excitatory information is modulated by lateral inhibition. To test the hypothesis that lateral inhibition may limit SSP, we delivered different patterns of noxious thermal stimuli to the abdomens of 15 subjects using a computer-controlled CO2 laser. Lines (5 mm wide) of variable lengths (4, 8 cm) were compared with 2-point stimuli delivered at the same position/separation as the length of lines. When compared with one-point control stimuli, 2-point stimulus patterns produced statistically significant SSP, while no such summation was detected during line stimulus patterns. Direct comparison of pain intensity evoked by 2-point pattern stimuli with line pattern stimuli revealed that 2-point patterns were perceived as significantly more painful, despite the fact that the 2-point pattern stimulated far smaller areas of skin. Thus, the stimulation of the skin region between the endpoints of the lines appears to produce inhibition. These findings indicate that lateral inhibition limits SSP and is an intrinsic component of nociceptive information processing. Disruption of such lateral inhibition may contribute substantially to the radiation of some types of chronic pain.

Design and Test of a Closed-Loop FES System for Supporting Function of the Hemiparetic Hand Based on Automatic Detection using the Microsoft Kinect sensor.

This paper describes the design of a FES system automatically controlled in a closed loop using a Microsoft Kinect sensor, for assisting both cylindrical grasping and hand opening. The feasibility of the system was evaluated in real-time in stroke patients with hand function deficits. A hand function exercise was designed in which the subjects performed an arm and hand exercise in sitting position. The subject had to grasp one of two differently sized cylindrical objects and move it forward or backwards in the sagittal plane. This exercise was performed with each cylinder with and without FES support. Results showed that the stroke patients were able to perform up to 29% more successful grasps when they were assisted by FES. Moreover, the hand grasp-and-hold and hold-and-release durations were shorter for the smaller of the two cylinders. FES was appropriately timed in more than 95% of all trials indicating successful closed loop FES control. Future studies should incorporate options for assisting forward reaching in order to target a larger group of stroke patients.

Membrane properties in small cutaneous nerve fibers in humans.

INTRODUCTION: Assessment of membrane properties is important for understanding the mechanisms of painful peripheral neuropathy, developing new diagnostic techniques, and screening/profiling of analgesics that target ion channels. METHODS: Small cutaneous nerves were activated electrically by small diameter (0.2 mm) cathodes, and large nerves were activated by ordinary patch electrodes. This new perception threshold tracking method combines perception threshold assessment and stimulation paradigms from conventional threshold tracking. RESULTS: The strength-duration time-constant of large fibers (580 µs ± 160 µs) was lower than the time constant of small fibers (1060 µs ± 690 µs; P < 0.01, paired t-test). Threshold electrotonus showed similar threshold reductions to sub-threshold prepulses, except for 80 ms hyperpolarizing prepulses, to which small fibers showed less threshold reduction than large fibers (repeated-measures analysis of variance, Bonferroni, P = 0.006). CONCLUSIONS: This is a reliable method to investigate the membrane properties of small cutaneous nerve fibers in humans and may be used in clinical settings as a diagnostic or profiling tool. Muscle Nerve 55: 195-201, 2017.

Design and Test of a Closed-Loop FES System for Supporting Function of the Hemiparetic Hand Based on Automatic Detection using the Microsoft Kinect sensor.

This paper describes the design of a FES system automatically controlled in a closed loop using a Microsoft Kinect sensor, for assisting both cylindrical grasping and hand opening. The feasibility of the system was evaluated in real-time in stroke patients with hand function deficits. A hand function exercise was designed in which the subjects performed an arm and hand exercise in sitting position. The subject had to grasp one of two differently sized cylindrical objects and move it forward or backwards in the sagittal plane. This exercise was performed with each cylinder with and without FES support. Results showed that the stroke patients were able to perform up to 29% more successful grasps when they were assisted by FES. Moreover, the hand grasp-and-hold and hold-and-release durations were shorter for the smaller of the two cylinders. FES was appropriately timed in more than 95% of all trials indicating successful closed loop FES control. Future studies should incorporate options for assisting forward reaching in order to target a larger group of stroke patients.

Feasibility of Using Lokomat Combined with Functional Electrical Stimulation for the Rehabilitation of Foot Drop.

This study investigated the clinical feasibility of combining the electromechanical gait trainer Lokomat with functional electrical therapy (LokoFET), stimulating the common peroneal nerve during the swing phase of the gait cycle to correct foot drop as an integrated part of gait therapy. Five patients with different acquired brain injuries trained with LokoFET 2-3 times a week for 3-4 weeks. Pre- and post-intervention evaluations were performed to quantify neurophysiological changes related to the patients' foot drop impairment during the swing phase of the gait cycle. A semi-structured interview was used to investigate the therapists' acceptance of LokoFET in clinical practice. The patients showed a significant increase in the level of activation of the tibialis anterior muscle and the maximal dorsiflexion during the swing phase, when comparing the pre- and post-intervention evaluations. This showed an improvement of function related to the foot drop impairment. The interview revealed that the therapists perceived the combined system as a useful tool in the rehabilitation of gait. However, lack of muscle selectivity relating to the FES element of LokoFET was assessed to be critical for acceptance in clinical practice.

Discriminative ability of reflex receptive fields to distinguish patients with acute and chronic low back pain.

Low back pain has a life time prevalence of 70% to 85%. Approximately 10% to 20% of all patients experience recurrent episodes or develop chronic low back pain. Sociodemographic, clinical, and psychological characteristics explain the transition from acute to chronic low back pain only to a limited extent. Altered central pain processing may be a contributing mechanism. The measurement of reflex receptive fields (RRF) is a novel method to assess altered central pain processing. The RRF area denotes the area of the foot sole from which spinal nociceptive reflexes can be elicited. It was shown to be enlarged in patients with acute and chronic low back pain compared with pain-free individuals. The aim of the study was to explore the discriminative ability of the RRF to distinguish patients with acute and chronic low back pain with the hypothesis that enlarged RRF are associated with chronic low back pain. We included 214 patients with either acute or chronic low back pain and compared RRF between groups in both univariable and multivariable analyses adjusted for different sociodemographic and clinical characteristics possibly associated with the transition to chronic pain. We found a mean difference between patients with acute and chronic low back pain of -0.01 (95% confidence interval [CI], -0.06 to 0.04) in the crude, -0.02 (95% CI, -0.08 to 0.04) in the age and sex adjusted, and -0.02 (95% CI, -0.09 to 0.05) in the fully adjusted model. Our results suggest that the enlargement of RRF area may not be associated with the transition from acute to chronic low back pain.

On the Agreement between Manual and Automated Methods for Single-Trial Detection and Estimation of Features from Event-Related Potentials.

The agreement between humans and algorithms on whether an event-related potential (ERP) is present or not and the level of variation in the estimated values of its relevant features are largely unknown. Thus, the aim of this study was to determine the categorical and quantitative agreement between manual and automated methods for single-trial detection and estimation of ERP features. To this end, ERPs were elicited in sixteen healthy volunteers using electrical stimulation at graded intensities below and above the nociceptive withdrawal reflex threshold. Presence/absence of an ERP peak (categorical outcome) and its amplitude and latency (quantitative outcome) in each single-trial were evaluated independently by two human observers and two automated algorithms taken from existing literature. Categorical agreement was assessed using percentage positive and negative agreement and Cohen's κ, whereas quantitative agreement was evaluated using Bland-Altman analysis and the coefficient of variation. Typical values for the categorical agreement between manual and automated methods were derived, as well as reference values for the average and maximum differences that can be expected if one method is used instead of the others. Results showed that the human observers presented the highest categorical and quantitative agreement, and there were significantly large differences between detection and estimation of quantitative features among methods. In conclusion, substantial care should be taken in the selection of the detection/estimation approach, since factors like stimulation intensity and expected number of trials with/without response can play a significant role in the outcome of a study.

Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors.

Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics.

Ipsilateral resistance exercise prevents exercise-induced central sensitization in the contralateral limb: a randomized controlled trial.

PURPOSE: This study aimed to investigate the hypothesis that a repeated bout of eccentric exercise (ECC2) would result in smaller increase in the sensitivity of spinal nociceptive system, and smaller decrease in the local muscle blood oxygenation response in both the ipsilateral and the contralateral tibialis anterior muscle (TA) when compared with the initial bout (ECC1). It was hypothesized that the magnitude of the repeated bout effect (RBE) would be greater for the ipsilateral side than the contralateral side. METHODS: Twenty-six healthy young men performed two bouts of high-intensity eccentric exercise of TA separated by 2 weeks. Half of the participants used the same leg for both bouts (IPSI) and the other half used the contralateral leg for ECC2 (CONTRA). Nociceptive withdrawal reflex threshold (NWRT) and local muscle blood oxygenation were assessed for the exercised TA muscle before, immediately after, and one day after exercise. RESULTS: Significant decreases in NWRT and muscle oxygenation were observed after ECC1 (p < 0.05), but NWRT did not change after ECC2 in both groups. Smaller decreases in muscle oxygenation were observed after ECC2 than ECC1 in both groups with a similar magnitude of the difference between bouts, but an increase in muscle oxygen re-perfusion before ECC2 was only observed in the IPSI group. CONCLUSION: These results suggest that contralateral RBE was associated with spinal facilitation of the neuronal pathways situated at a homologous innervation level, and it is unlikely that oxygen re-perfusion improvement plays a major role in the contralateral RBE.

Stimulation site and phase modulation of the withdrawal reflex during gait initiation.

OBJECTIVE: To investigate how the nociceptive withdrawal reflex (NWR) is modulated during gait initiation. METHODS: The NWR was elicited in ten subjects using electrical stimulation at four sites in the right foot during symmetrical stance (50% of body weight on each foot) or while performing the first step during gait initiation: either during heel off (HO, 20% of body load on the starting leg) or heel contact (HC, 80% of body load on the starting leg in the first step). Kinematics and EMG responses from major muscles of the ipsilateral leg were recorded. RESULTS: The NWR was modulated by stimulation site in all muscles except Soleus. The NWR responses elicited after stimulation of the arch were significantly larger than those evoked at all other sites in Tibialis Anterior, Rectus Femoris, and Vastus Lateralis. At the hip joint, the largest flexion was obtained during HO, whereas the smallest flexion was observed during HC, both following stimulation on the arch of the foot. CONCLUSIONS: The NWR responses were modulated to maintain balance and continue the development of the gait initiation process. SIGNIFICANCE: The NWR modulation followed a functional principle, which might allow a functional use in rehabilitation strategies.

Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients.

OBJECTIVES: Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. METHODS: Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. RESULTS: Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. DISCUSSION: The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.

Repeated electrical stimulations as a tool to evoke temporal summation of nociceptive inputs in healthy, non-medicated experimental sheep.

The nociceptive withdrawal reflex (NWR) model is used in animal pain research to quantify nociception. The aim of this study was to evaluate the NWR evoked by repeated stimulations in healthy, non-medicated standing sheep. Repeated electrical stimulations were applied at 5 Hz for 2s to the digital nerves of the right thoracic and the pelvic limbs of 25 standing sheep. The stimulation intensities applied were fractions (0.5, 0.6, 0.7, 0.8, 0.9 and 1) of the individual previously determined nociceptive threshold (It) after single stimulation. Surface-electromyographic activity (EMG) was recorded from the deltoid, the femoral biceps or the peroneus tertius muscles. The repeated stimulation threshold (RS It) was reached if at least one stimulus in the train was followed by a reflex with a minimal root-mean-square-amplitude (RMSA) of 20 µV. The behavioural reaction following each series of stimulations was scored on a scale from 0 (no reaction) to 5 (vigorous whole-body reaction). For the deltoid muscle, RS It was 2.3 mA (1.6-3 mA) with a reaction score of 2 (1-2) and at a fraction of 0.6 (0.5-0.8)×It. For the biceps femoris muscle, RS It was 2.9 mA (2.6-4 mA) with a reaction score of 1 (1-2) at a fraction of and 0.55 (0.4-0.7)×It while for the peroneus tertius muscle RS It was 3 mA (2.8-3.5 mA) with a reaction score of 1 (1-2) and at a fraction of 0.8 (0.8-0.95)×It. Both, RMSA and reaction scores increased significantly with increasing stimulation intensities in all muscles (p<0.001). The repeated application of electrical stimuli led to temporal summation of nociceptive inputs and therefore a reduction of the stimulus intensity evoking a withdrawal reaction in healthy, standing sheep. Data achieved in this study can now serve as reference for further clinical or experimental applications of the model in this species.

On the use of information theory for the analysis of synchronous nociceptive withdrawal reflexes and somatosensory evoked potentials elicited by graded electrical stimulation.

BACKGROUND: To date, few studies have combined the simultaneous acquisition of nociceptive withdrawal reflexes (NWR) and somatosensory evoked potentials (SEPs). In fact, it is unknown whether the combination of these two signals acquired simultaneously could provide additional information on somatosensory processing at spinal and supraspinal level compared to individual NWR and SEP signals. NEW METHOD: By using the concept of mutual information (MI), it is possible to quantify the relation between electrical stimuli and simultaneous elicited electrophysiological responses in humans based on the estimated stimulus-response signal probability distributions. RESULTS: All selected features from NWR and SEPs were informative in regard to the stimulus when considered individually. Specifically, the information carried by NWR features was significantly higher than the information contained in the SEP features (p<0.05). Moreover, the joint information carried by the combination of features showed an overall redundancy compared to the sum of the individual contributions. Comparison with existing methods MI can be used to quantify the information that single-trial NWR and SEP features convey, as well as the information carried jointly by NWR and SEPs. This is a model-free approach that considers linear and non-linear correlations at any order and is not constrained by parametric assumptions. CONCLUSIONS: The current study introduces a novel approach that allows the quantification of the individual and joint information content of single-trial NWR and SEP features. This methodology could be used to decode and interpret spinal and supraspinal interaction in studies modulating the responsiveness of the nociceptive system.

Adaptation of local muscle blood flow and surface electromyography to repeated bouts of eccentric exercise.

The aim of this randomized controlled crossover study was to investigate the effect of a bout of unaccustomed eccentric exercise (ECC) followed by a consecutive bout of the same intensity on local muscle blood flow, amplitude, and frequency of the electromyographic (EMG) signal from the exercised tibialis anterior muscle. Sixteen healthy male participants (age, 25.7 (0.6) years; body mass index 24.8 (1) kg·m(-2) participated in this study. Two identical bouts of high-intensity ECC were performed on the tibialis anterior muscle 7 days apart. Control sessions involving no exercise were performed 4 weeks either before or after the exercise sessions. Changes in local total blood flow [ΔtHb], EMG root mean square, and median power frequency were recorded during isometric maximum voluntary contraction of ankle dorsiflexion. Measurements were performed before, immediately after, and the day after both ECCs (ECC1 and ECC2). The participants rested quietly in a chair in the control session. Eccentric exercise 1 led to a significant decrease in [ΔtHb] on the day after (p ≤ 0.05), whereas ECC2 did not. Median power frequency decreased significantly in ECC2 compared with ECC1 (p < 0.01). Root mean square was unchanged in all the instants. The present study showed that adaptation is depicted in the local muscle blood flow and the frequency contents of the EMG after an unaccustomed ECC inducing muscle soreness. These alterations provide a potential mechanism for a rapid adaptation, which decreases susceptibility of the muscle to develop further soreness in the subsequent ECC bout.