Influence of sensory retraining on cortical reorganization in peripheral neuropathy: A systematic review.

OBJECTIVE: This study systematically reviewed the literature about sensory retraining effect in comparison to other rehabilitative techniques on cortical reorganization in patients with peripheral neuropathic pain. TYPE: Systematic review. LITERATURE SURVEY: After performing an electronic search of PubMed, Web of Science, and Embase, risk of bias was assessed using the revised Cochrane risk of bias tool for randomized controlled trials and the risk of bias in non-randomized studies-of interventions for non-randomized studies of intervention. METHODOLOGY: The strength of conclusion was determined using the evidence-based guideline development approach. SYNTHESIS: Limited evidence indicates a higher increase in cortical inhibition and a higher reduction in cortical activation during a motor task of the affected hemisphere after graded motor imagery compared to wait-list. Higher reductions in map volume (total excitability of the cortical representation) of the affected hemisphere after peripheral electrical stimulation (PES) were observed when compared to transcranial direct current stimulation (tDCS) or to sham treatment with limited evidence. No other differences in cortical excitability and representation of the affected and non-affected hemisphere were observed when comparing mirror therapy with sham therapy or tDCS, PES with sham therapy or tDCS, and graded motor imagery with wait-list. CONCLUSIONS: Graded motor imagery and PES result in higher cortical excitability reductions of the affected hemisphere compared to wait-list, tDCS and sham treatment, respectively.

Modulation of the nociceptive flexion reflex by conservative therapy in patients and healthy people: a systematic review and meta-analysis.

ABSTRACT: The nociceptive flexion reflex (NFR) is a spinally mediated withdrawal response and is used as an electrophysiological marker of descending modulation of spinal nociception. Chemical and pharmacological modulation of nociceptive neurotransmission at the spinal level has been evidenced by direct effects of neurotransmitters and pharmacological agents on the NFR. Largely unexplored are, however, the effects of nonpharmacological noninvasive conservative interventions on the NFR. Therefore, a systematic review and meta-analysis was performed and reported following the PRISMA guidelines to determine whether and to what extent spinal nociception measured through the assessment of the NFR is modulated by conservative therapy in patients and healthy individuals. Five electronic databases were searched to identify relevant articles. Retrieved articles were screened on eligibility using the predefined inclusion criteria. Risk of bias was investigated according to Version 2 of the Cochrane risk-of-bias assessment tool for randomized trials. The evidence synthesis for this review was conducted in accordance with the Grading of Recommendations Assessment, Development and Evaluation. Thirty-six articles were included. Meta-analyses provided low-quality evidence showing that conservative therapy decreases NFR area and NFR magnitude and moderate-quality evidence for increases in NFR latency. This suggests that conservative interventions can exert immediate central effects by activating descending inhibitory pathways to reduce spinal nociception. Such interventions may help prevent and treat chronic pain characterized by enhanced spinal nociception. Furthermore, given the responsiveness of the NFR to conservative interventions, the NFR assessment seems to be an appropriate tool in empirical evaluations of treatment strategies.PROSPERO registration number: CRD42020164495.

Does muscular or mental fatigue have an influence on the nociceptive flexion reflex? A randomized cross-over study in healthy people.

BACKGROUND: The nociceptive flexion reflex (NFR) is a spinally-mediated withdrawal reflex occurring in response to noxious stimuli and is used as an electrophysiological marker of spinal nociception. Although it is well-documented that the NFR is subject to powerful modulation of several personal factors, the effects of experimentally induced fatigue on the NFR have not yet been examined. Hence, this study aimed to characterize if and how fatigue affects spinal nociception in healthy adults. METHODS: The NFR of 58 healthy people was measured prior to and following rest and two fatiguing tasks performed in randomized order. The NFR was elicited by transcutaneous electrical stimulation of the sural nerve and objectified by electromyographic recordings from the biceps femoris muscle. An isokinetic fatiguing protocol was used to induce localized muscle fatigue of the hamstrings. The modified incongruent Stroop-word task was used to provoke mental fatigue. A linear mixed model analysis was performed to assess the influence of fatigue on the NFR. RESULTS: Low-to-moderate levels experimentally induced localized muscle and mental fatigue did not affect the NFR in healthy adults. These results suggest that descending pain inhibitory processes to dampen spinal nociception are resistant to the effects of localized muscle and mental fatigue. CONCLUSIONS: The relative robustness of the NFR to fatigue may be beneficial in both clinical and research settings where the influence of confounders complicates interpretation. Furthermore, the findings possibly help enhance our understanding on why even demanding cognitive/physical exercise-based treatment programs form effective treatment strategies for patients with chronic pain. SIGNIFICANCE: The present study unraveled that low-to-moderate levels experimentally induced localized muscle and mental fatigue did not affect the NFR. These results suggest that descending pain inhibitory processes to dampen spinal nociception are resistant to the effects of localized muscle and mental fatigue. This relative robustness of the NFR may be beneficial in a clinical setting in which the evaluation of spinal nociception that is unaffected by clinical symptoms of fatigue may be useful (e.g. chronic fatigue syndrome, cancer-related fatigue, etc.).

The influence of physical activity on the nociceptive flexion reflex in healthy people.

BACKGROUND: The nociceptive flexion reflex (NFR) is a spinal reflex induced by painful stimuli resulting in an appropriate withdrawal response. The NFR is considered to be an objective physiological correlate of spinal nociception. Previous research has already demonstrated that physical activity (PA) can influence pain assessments. To date, no studies have directly examined the relationship between PA and spinal nociception. Hence, this study aimed to investigate whether the NFR threshold can be predicted by report-based and monitor-based measures of PA in healthy adults. METHODS: PA and the NFR threshold of 58 healthy adults were assessed. PA was evaluated by self-report using the International Physical Activity Questionnaire and by monitor-based accelerometry data. The NFR threshold was elicited through transcutaneous electrical stimulation of the sural nerve and quantified by the biceps femoris muscle electromyogram. Hierarchical linear regression analyses were performed to determine the relationship between PA and the NFR, while controlling for confounders. RESULTS: Monitor-based measured step count and activities of moderate- to vigorous-intensity predicted the NFR threshold accounting for 23.0% (p = .047) to 37.1% (p = .002) of the variance. Larger amounts of step counts and higher participation in moderate- to vigorous-intensity activities predicted higher NFR thresholds. Monitor-based activities of sedentary intensity predicted the NFR threshold accounting for 35.8% (p = .014) to 35.9% (p = .014) of the variance. Spending more time per day on activities of sedentary intensity predicted lower NFR thresholds. CONCLUSIONS: The study provides preliminary evidence indicating that a physically active lifestyle may reduce spinal nociception in healthy adults, while a sedentary lifestyle enhances spinal nociception. SIGNIFICANCE: The present study provides preliminary evidence that the influencing effects of physical activity on pain are the result of a strong descending control and do not purely rely on supraspinal mechanisms. These study results highlight the importance of considering physical activity levels when evaluating nociceptive processing, given the prognostic value of physical activity in spinal nociception. Furthermore, this study encourages future research to examine the effects of moderate- to vigorous-intensity exercise programmes on spinal nociception in chronic pain populations.

Pain Neuroscience Education for Children with Functional Abdominal Pain Disorders: A Randomized Comparative Pilot Study.

This article explores the effectiveness of a newly developed Pain Neuroscience Education program for children (PNE4Kids) with functional abdominal pain disorder (FAPD). Children (6-12 years) with FAPD were randomly assigned to 1) the experimental group (n = 14), participating in one hypnotherapy session (i.e., usual care) and one additional PNE4Kids session, or 2) the control group (n = 14), participating in two hypnotherapy sessions. Parental pain catastrophizing, the child's functional disability (parental-proxy), pain-related fear (parent-proxy) and pain intensity, were assessed at baseline and one and three weeks after each therapy session. Pressure algometry and a conditioned pain modulation paradigm were performed at baseline and three weeks after completion of the last therapy session. Parents from both the experimental as well as the control group showed significantly less parental pain catastrophizing (p < 0.01). Children showed significantly less functional disability (p < 0.05), pain-related fear (p < 0.01) and local pressure pain sensitivity (p < 0.05) at short-term follow-up (three weeks after last intervention) in both groups. No significant (p > 0.05) between-group differences were found. Hypnotherapy combined with PNE4Kids did not result in better clinical outcomes compared to hypnotherapy alone. Study limitations include the application of one single PNE4Kids session and the short follow-up time.

Acupuncture Versus Sham Acupuncture: A Meta-Analysis on Evidence for Longer-term Effects of Acupuncture in Musculoskeletal Disorders.

EDITORIAL NOTE: The original Letter to the Editor prepared by Jones et al was based on the initial electronic version then contained several important procedural errors that resulted in erroneous conclusions as noted by Jones et al in their original Letter. Subsequently, the authors of the Letter to the Editor were notified of the corrections and they then prepared the revised Letter to the Editor published here. Jones et al did note a remaining error in Table 5 of their corrected manuscript. Based on Jones et al's observation, Lenoir et al were notified of an error on Table 5 and have addressed this in the current version of their paper published in this issue. We appreciate the input of the authors of the letter and the positive response of the author(s) of this article. Dennis C. Turk, PhD Editor-in-Chief OBJECTIVE:: Acupuncture is a common modality in the therapy of musculoskeletal disorders. The evidence for acupuncture has been examined frequently, but a clear synthesis of previous research is currently lacking. This meta-analysis aimed to summarize the evidence for nonimmediate effects of acupuncture on pain, functionality, and quality of life in patients with musculoskeletal disorders, when compared with sham acupuncture. METHODS: Search results from PubMed and Web of Science were brought together. All screening procedures were executed twice by 2 independent researchers. The pooled standardized mean difference (SMD) with its confidence interval (CI) was estimated at follow-up at <1 month, 1 to 3 months, 3 to 6 months, and >6 months. RESULTS: For pain, the SMD equalled respectively -0.47 (CI -0.76 to -0.19), -0.27 (CI -0.44 to -0.11), -0.32 (CI -0.51 to -0.13) and -0.12 (CI -0.36 to 0.11) for <1 month, 1 to 3 months, 3 to 6 months, and >6 months follow-up. For functionality, the pooled SMD equalled -0.43 (CI -0.76 to -0.10), -0.41 (CI -0.76 to -0.05), 0.07 (CI -0.22 to 0.36), and -0.13 (-0.46 to 0.19). In the area of QOL, pooled SMD of respectively 0.20 (CI 0.04 to 0.35), 0.19 (CI -0.01 to 0.39), 0.02 (CI -0.09 to 0.14) and -0.04 (CI -0.25 to 0.16) were obtained. DISCUSSION: A significant difference in therapy effect, favoring acupuncture, was found for pain at <1 month, 1 to 3 months, and 3 to 6 months, as well as on quality of life at <1 month, and on functionality at <1 month and 1 to 3 months.

Are Functional Brain Alterations Present in Low Back Pain? A Systematic Review of EEG Studies.

This systematic review analyzed available literature on functional brain alterations in low back pain (LBP) measured with electroencephalography (EEG), as until now evidence thereof was unclear. Four electronic databases were systematically searched the 10th of March 2018, resulting in 12 included studies. Studies showed a risk of bias of 37.5 to 75% using the Newcastle-Ottawa Scale for case-control studies. Limited evidence reported higher amplitudes of balance-related potentials and early components of somatosensory evoked potentials (SEP) to noxious stimuli, and altered feedback-related negativity and P300 potentials during decision-making in chronic LBP (CLBP). These findings suggest postural strategies requiring a higher cortical attention-demand, increased sensory-discriminative processing of noxious input, and altered decision-making in CLBP. However, further research is warranted as these inferences were based on single studies. Moderate evidence for unaltered amplitude of late-phase SEPs to noxious stimuli and auditory evoked potentials in LBP implies that the affective-emotional processing of stimuli might be unaffected in LBP. Furthermore, moderate evidence indicated disturbed habituation of somatosensory stimuli in LBP. Most studies examined nonspecific or mixed CLBP populations, hence EEG-quantified brain activity in (sub)acute or recurrent LBP still needs to be explored. PERSPECTIVE: This review presents an overview of the current understanding of the functional LBP brain measured with EEG. The limited evidence in current research suggests altered cortical function regarding balance control, somatosensory processing, and decision making in LBP, and highlights opportunities for future EEG-research.

Physical and cognitive exertion do not influence feedforward activation of the trunk muscles: a randomized crossover trial.

Fatigue arises during everyday activities, diminishes movement performance, and increases injury risk. Physical (PE) and cognitive exertion (CE) can induce similar feelings of fatigue, but it is not clear whether these also similarly affect movement performance. Therefore, this study examined the influence of PE and CE on anticipatory postural adjustments (APAs) of trunk muscles, which are feedforward mechanisms that contribute to motor control and controlled movement. Rapid arm movement tasks (RAM) were used to induce APAs of the trunk muscles prior and following three experimental conditions in 20 healthy adults: seated rest without exertion (NE), a combined isometric modified Biering-Sörensen and static abdominal curl to induce PE, and a modified incongruent Stroop colour-word task to induce CE. Fatigue was assessed using self-reported measures, and APA onset latencies of the trunk muscles with surface electromyography. Statistical analyses revealed that neither PE nor CE influence APAs of the trunk. Therefore, it is hypothesized that the influence of fatigue on movement performance might not be through altered motor control, but rather by reduced motivation. However, the possibility that fatigue might influence other mechanisms which contribute to trunk motor control, such as APA amplitude and variability, cannot be excluded and need further examination.

Endogenous pain modulation in children with functional abdominal pain disorders.

Functional abdominal pain disorders (FAPDs) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry, and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age- and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds (PPTs) at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. Conditioned pain modulation was recorded as an increase in the PPT at the trapezius test site in response to experimental conditioning pain imposed by the cold pressor task (12 ± 1°C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear, and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower PPTs at all test sites (P < 0.05), a lower CPM response (P = 0.02), more functional disability (P < 0.001), and pain-related fear (P < 0.001). Parents of children with FAPD catastrophized more about their child's pain than parents of healthy children (P < 0.001). No sex differences were found for the experimental pain measurements (P > 0.05), nor was there a significant correlation between the child- and parent-reported questionnaires and the CPM effect (P > 0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.

Effects of Conditioned Pain Modulation on the Nociceptive Flexion Reflex in Healthy People: A Systematic Review.

OBJECTIVES: The nociceptive flexion reflex (NFR) is a spinal reflex induced by painful stimuli resulting in a withdrawal response. Research has shown that the NFR is inhibited through endogenous pain inhibitory mechanisms, which can be assessed by conditioned pain modulation (CPM) paradigms. Although accumulating research suggests that the NFR can be affected by CPM, no clear overview of the current evidence exists. Therefore, the present review aimed at providing such a synthesis of the literature. In addition, the influence of personal factors on the CPM of the NFR was investigated. MATERIALS AND METHODS: A systematic review was performed and reported following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases were searched to identify relevant articles. Retrieved articles were screened on eligibility using predefined inclusion criteria. Risk of bias was investigated according to the modified Newcastle-Ottawa Scale. Levels of evidence and strength of conclusion were assigned following the guidelines of the Dutch Institute for Healthcare Improvement. RESULTS: Forty articles were included. There is some evidence that CPM produced by thermal or mechanical stimuli induces inhibitory effects on the NFR. However, inconclusive evidence exists with regard to the effect of electrical conditioning stimuli. While several personal factors do not affect CPM of the NFR, increased cognitive interference is associated with reduced NFR inhibition. DISCUSSION: The present review demonstrates that certain types of nociceptive conditioning stimuli have the potential to depress, at the spinal level, nociceptive stimuli elicited from distant body regions. Although CPM of the NFR seems to be robust to the influence of several personal factors, it can be affected by cognitive influences.

Hyperexcitability of the Central Nervous System in Children with Chronic Pain: A Systematic Review.

Objective: Hyperexcitability of the central nervous system plays an important role in the development and maintenance of chronic pain in adults. This knowledge has led to improved treatment strategies within this population. In children, however, research on the presence of central hyperexcitability is scarce. To further investigate this topic in children with chronic pain, there is a need for a clear literature overview. Design: Systematic review. Methods: The literature search was performed using the electronic databases PubMed and Web of Science. An article was considered eligible if it included children (age two to 12 years) diagnosed with chronic pain. Articles had to report original research outcomes related to central hyperexcitability, and a comparison with a healthy control group was necessary. Characteristics of the study sample, the assessment, and conclusions regarding central hyperexcitability were extracted from each included article. Results: Twelve case-control studies were included with moderate to good methodological quality (510 children with chronic pain and 670 healthy controls). After summarizing the articles' results on indices of central hyperexcitability, we concluded that secondary hyperalgesia might be present in children with recurrent abdominal pain, juvenile fibromyalgia, and juvenile idiopathic arthritis. Preliminary evidence exists for altered cortical nociceptive processing in children with migraine and recurrent abdominal pain. Conclusion: Based on the results of this review, central hyperexcitability might be present in in several pediatric chronic pain conditions. Further research on other manifestations of central hyperexcitability (e.g., bottom-up and top-down mechanisms and nociceptive brain changes) is necessary to provide firm evidence about its presence in children with chronic pain.

Inter- and intrarater reliability of two proprioception tests using clinical applicable measurement tools in subjects with and without knee osteoarthritis.

BACKGROUND: The therapeutic value of proprioceptive-based exercises in knee osteoarthritis (KOA) management warrants investigation of proprioceptive testing methods easily accessible in clinical practice. OBJECTIVE: To estimate inter- and intrarater reliability of the knee joint position sense (KJPS) test and knee force sense (KFS) test in subjects with and without KOA. DESIGN: Cross-sectional test-retest design. METHOD: Two blinded raters performed independently repeated measures of the KJPS and KFS test, using an analogue inclinometer and handheld dynamometer, respectively, in eight KOA patients (12 symptomatic knees) and 26 healthy controls (52 asymptomatic knees). Intraclass correlation coefficients (ICCs; model 2,1), standard error of measurement (SEM) and minimal detectable change with 95% confidence bounds (MDC95) were calculated. RESULTS: For KJPS, results showed good to excellent test-retest agreement (ICCs 0.70-0.95 in KOA patients; ICCs 0.65-0.85 in healthy controls). A 2° measurement error (SEM 1°) was reported when measuring KJPS in multiple test positions and calculating mean repositioning error. Testing KOA patients pre and post therapy a repositioning error larger than 4° (MDC95) is needed to consider true change. Measuring KFS using handheld dynamometry showed poor to fair interrater and poor to excellent intrarater reliability in subjects with and without KOA. CONCLUSIONS: Measuring KJPS in multiple test positions using an analogue inclinometer and calculating mean repositioning error is reliable and can be used in clinical practice. We do not recommend the use of the KFS test to clinicians. Further research is required to establish diagnostic accuracy and validity of our KJPS test in larger knee pain populations.