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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 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 ROBINS-1 (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., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Background: The hypermobile type of Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder, associated with joint hypermobility and prominent chronic pain. Because experimental pain testing in hEDS is scarce, the underlying mechanisms are still poorly understood., Objective: The present study assesses endogenous pain facilitation and pain inhibition in hEDS, using a protocol for temporal summation of pain (TSP), conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH)., Methods: Twenty women with hEDS and 20 age-matched healthy controls participated. After evaluating thermal and mechanical pain thresholds (PPT), TSP was assessed using 10 repetitive painful pressure stimuli. CPM was provoked using pressure as the test stimulus and hand immersion in hot water (46°) as the conditioning stimulus. EIH was assessed after a submaximal cycling protocol., Results: The hEDS group demonstrated reduced PPTs and showed significantly more TSP after repeated painful stimuli than the control group. In comparison to the healthy control group, the hEDS group demonstrated significantly less EIH at the quadriceps test location. At the trapezius, EIH did not significantly differ between groups. No significant differences were found between the hEDS group and control group in the CPM response., Conclusion: The results demonstrate increased TSP in hEDS, suggesting increased central pain facilitation. EIH should be studied more extensively but may be disturbed when evaluated in the muscles that are activated during exercise. The CPM results are inconclusive and require more research., Significance: Studies regarding the mechanisms that underlie pain in hEDS are scarce, although it is the most prevalent and disabling symptom in this patient population. This study demonstrates increased temporal summation in hEDS and suggests that exercise-induced hypoalgesia may be reduced. Because exercise is a cornerstone in the multidisciplinary treatment of heritable connective tissue disorders, gaining knowledge in this field is important. Pressure stimuli were used to facilitate the international usability of the protocols, allowing for future data acquisition in large cohorts., (© 2022 European Pain Federation - EFIC®.)

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.)., (© 2021 European Pain Federation - EFIC®.)

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., (© 2020 European Pain Federation - EFIC®.)

Background: Conditioned pain modulation (CPM) methods are experimental procedures to assess presumed descending nociceptive modulatory pathways. Various CPM-methods are currently used, making the comparison of results difficult. The aim of this study was to compare five conditioning stimuli and to evaluate the influencing effects of personal factors on CPM-efficacy., Methods: 101 healthy pain-free adults (50 males, 51 females) participated in this cross-sectional study with repeated measures design. The CPM-method consisted of hot water immersion (46°C, HWI), cold pressor test (12°C, CPT), cold pack application, and single and double ischemic occlusion as conditioning stimuli in randomized order. Pressure pain threshold was used as test stimulus at the mm. trapezius and quadriceps for all CPM-protocols., Results: All CPM-protocols resulted in effective CPM, although cold pack application revealed smaller CPM-magnitudes compared to all other methods at both muscles, except single ischemic occlusion at the m. quadriceps. A smaller CPM-effect at the m. trapezius was shown when CPM was provoked by single ischemic occlusion compared to the CPT. Chronic stress, gender, attentional focus, age, physical activity and perceived pain are all influencing factors, in various conditioning stimuli at the mm. trapezius and quadriceps., Conclusions: CPT and HWI seem to be the most appropriate conditioned pain modulation paradigms for research settings, while single and double ischemic occlusion seem to be more useful for clinical settings. Influencing factors to be considered are gender, age, stress, physical activity, perceived pain and attentional focus to the conditioning stimulus, but depend on the test site and exerted method., Significance: Hot water immersion, cold pressor test, and single and double ischemic occlusion result in comparable CPM-effects at the mm. trapezius and quadriceps. Anti-nociceptive effects of the cold pack are mainly a result of attention towards the cold pack. Chronic stress, attentional focus towards the conditioning stimulus and perceived pain of the conditioning stimulus influenced the anti-nociceptive effects at the m. trapezius. Gender and level of physical activity influenced the anti-nociceptive effects with the other methods at the m. quadriceps., (© 2020 European Pain Federation - EFIC®.)

Background and Objectives: It has been suggested that sensitization of the central nervous system plays an important role in the development and maintenance of chronic (pain) complaints experienced by whiplash patients. According to the PRISMA guidelines, a systematic review was performed to screen and evaluate the existing clinical evidence for the presence of central sensitization in chronic whiplash. DATABASES AND DATA TREATMENT: Predefined keywords regarding central sensitization and chronic whiplash were combined in electronic search engines PubMed and Web of Science. Full text clinical reports addressing studies of central sensitization in human adults with chronic complaints due to a whiplash trauma were included and reviewed on methodological quality by two independent reviewers., Results: From the 99 articles that were identified, 24 met the inclusion criteria, and 22 articles achieved sufficient scores on methodological quality and were discussed. These studies evaluated the sensitivity to different types of stimuli (mechanical, thermal, electrical). Findings suggest that although different central mechanisms seem to be involved in sustaining the pain complaints in whiplash patients, hypersensitivity of the central nervous system plays a significant role. Persistent pain complaints, local and widespread hyperalgesia, referred pain and (thoracic) allodynia, decreased spinal reflex thresholds, inefficient diffuse noxious inhibitory controls activation and enhanced temporal summation of pain were established in chronic whiplash patients., Conclusions: Although the majority of the literature provides evidence for the presence of central sensitization in chronic whiplash, underlying mechanisms are still unclear and future studies with good methodological quality are necessary. In addition, international guidelines for the definition, clinical recognition, assessment and treatment of central sensitization are warranted., (© 2012 European Federation of International Association for the Study of Pain Chapters.)

Background: Central sensitisation entails several top-down and bottom-up mechanisms, all contributing to the hyperresponsiveness of the central nervous system to a variety of inputs. In the late nineties, it was first hypothesised that chronic fatigue syndrome (CFS) is characterised by hypersensitivity of the central nervous system (i.e. central sensitisation). Since then, several studies have examined central sensitisation in patients with CFS. This study provides an overview of such studies., Materials and Methods: Narrative review., Results: Various studies showed generalised hyperalgesia in CFS for a variety of sensory stimuli, including electrical stimulation, mechanical pressure, heat and histamine. Various tissues are affected by generalised hyperalgesia: the skin, muscle tissue and the lungs. Generalised hyperalgesia in CFS is augmented, rather than decreased, following various types of stressors like exercise and noxious heat pain. Endogenous inhibition is not activated in response to exercise and activation of diffuse noxious inhibitory controls following noxious heat application to the skin is delayed., Conclusions: The observation of central sensitisation in CFS is in line with our current understanding of CFS. The presence of central sensitisation in CFS corroborates with the presence of several psychological influences on the illness, the presence of infectious agents and immune dysfunctions and the dysfunctional hypothalamus-pituitary-adrenal axis as seen in these severely debilitated patients., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)