Early Intervention of Cold-Water Swimming on Functional Recovery and Spinal Pain Modulation Following Brachial Plexus Avulsion in Rats.

Brachial plexus avulsion (BPA) causes peripheral nerve injury complications with motor and sensory dysfunction of the upper limb. Growing evidence has shown an active role played by cold-water swimming (CWS) in alleviating peripheral neuropathic pain and functional recovery. This study examined whether CWS could promote functional recovery and pain modulation through the reduction of neuroinflammation and microglial overactivation in dorsal horn neurons at the early-stage of BPA. After BPA surgery was performed on rats, they were assigned to CWS or sham training for 5 min twice a day for two weeks. Functional behavioral responses were tested before and after BPA surgery, and each week during training. Results after the two-week training program showed significant improvements in BPA-induced motor and sensory loss (p < 0.05), lower inflammatory cell infiltration, and vacuole formation in injured nerves among the BPA-CWS group. Moreover, BPA significantly increased the expression of SP and IBA1 in dorsal horn neurons (p < 0.05), whereas CWS prevented their overexpression in the BPA-CWS group. The present findings evidenced beneficial rehabilitative effects of CWS on functional recovery and pain modulation at early-stage BPA. The beneficial effects are partially related to inflammatory suppression and spinal modulation. The synergistic role of CWS combined with other management approaches merits further investigation.

Global Research on Neuropathic Pain Rehabilitation over the Last 20 Years.

Background: Neuropathic pain has long been a very popular and productive field of clinical research. Neuropathic pain is difficult to cure radically because of its complicated etiology and uncertain pathogenesis. As pain worsens and persists, pain recovery techniques become more important, and medication alone is insufficient. No summary of bibliometric studies on neuropathic pain rehabilitation is yet available. The purpose of the present study is to analyze in a systematic manner the trends of neuropathic pain rehabilitation research over the period of 2000-2019. Methods: Studies related to neuropathic pain rehabilitation and published between January 2000 and December 2019 were obtained from the Science Citation Index-Expanded of Web of Science. No restrictions on language, literature type, or species were established. CiteSpace V and Microsoft Excel were used to capture basic information and highlights in the field. Results: Linear regression analysis showed that the number of publications on neuropathic pain rehabilitation significantly increased over time (P < 0.001). The United States showed absolute strength in terms of number of papers published, influence, and cooperation with other countries. Based on the subject categories of the Web of Science, "Rehabilitation" had the highest number of published papers (446), the highest number of citations (10,954), and the highest number of open-access papers (151); moreover, this category and "Clinical Neurology" had the same H-index (i.e., 52). "Randomized Controlled Trials" revealed the largest cluster in the cocitation map of references. The latest burst keywords included "Exercise" (2014-2019), "Functional Recovery" (2015-2019), and "Questionnaire" (2015-2019). Conclusion: This study provides valuable information for neuropathic pain rehabilitation researchers seeking fresh viewpoints related to collaborators, cooperative institutions, and popular topics in this field. Some new research trends are also highlighted.

Effectiveness of electrophysical modalities in the sensorimotor rehabilitation of radial, ulnar, and median neuropathies: A meta-analysis.

INTRODUCTION: People with ulnar, radial or median nerve injuries can present significant impairment of their sensory and motor functions. The prescribed treatment for these conditions often includes electrophysical therapies, whose effectiveness in improving symptoms and function is a source of debate. Therefore, this systematic review aims to provide an integrative overview of the efficacy of these modalities in sensorimotor rehabilitation compared to placebo, manual therapy, or between them. METHODS: We conducted a systematic review according to PRISMA guidelines. We perform a literature review in the following databases: Biomed Central, Ebscohost, Lilacs, Ovid, PEDro, Sage, Scopus, Science Direct, Semantic Scholar, Taylor & Francis, and Web of Science, for the period 1980-2020. We include studies that discussed the sensorimotor rehabilitation of people with non-degenerative ulnar, radial, or median nerve injury. We assessed the quality of the included studies using the Risk of Bias Tool described in the Cochrane Handbook of Systematic Reviews of Interventions and the risk of bias across studies with the GRADE approach described in the GRADE Handbook. RESULTS: Thirty-eight studies were included in the systematic review and 34 in the meta-analysis. The overall quality of evidence was rated as low or very low according to GRADE criteria. Low-level laser therapy and ultrasound showed favourable results in improving symptom severity and functional status compared to manual therapy. In addition, the low level laser showed improvements in pinch strength compared to placebo and pain (VAS) compared to manual therapy. Splints showed superior results to electrophysical modalities. The clinical significance of the results was assessed by effect size estimation and comparison with the minimum clinically important difference (MCID). CONCLUSIONS: We found favourable results in pain relief, improvement of symptoms, functional status, and neurophysiological parameters for some electrophysical modalities, mainly when applied with a splint. Our results coincide with those obtained in some meta-analyses. However, none of these can be considered clinically significant. TRIAL REGISTRATION: PROSPERO registration number CRD42020168792; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=168792.

Transcranial Direct Current Stimulation and Visual Illusion Effect According to Sensory Phenotypes in Patients With Spinal Cord Injury and Neuropathic Pain.

Treatment of neuropathic pain (NP) in patients with spinal cord injury (SCI) remains a major challenge. The aim of the present study is to investigate if the effect of transcranial direct current stimulation combined with visual illusion, following a previously published protocol, has differential effects on pain-related sensory symptoms according to sensory phenotypes profiles. One hundred and thirty SCI patients with NP participated in this open-label trial. Sixty-five patients were given a daily 20-minutes combined treatment of transcranial direct current stimulation and visual illusion for 2 weeks. Sixty-five patients served as a control group. Clinical assessment was performed before and 2 weeks later, by using Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory, and Patient Health Questionnaire-9. There was significant improvement in the combined treatment group according to NPSI, Brief Pain Inventory, and Patient Health Questionnaire-9, but no changes in the control group. Following a cluster analysis of NPSI items at baseline assessment, 5 subgroups of patients with different pain-related characteristics were identified among the treated group, although differences between clusters were not significant. There was also improvement in mood, sleep quality, and enjoyment of life in the treated group. Despite a reduction of NP with the combined treatment, the analysis of sensory phenotype pain profiles does not provide a predictive value regarding the analgesic results of this combined neuromodulatory treatment. PERSPECTIVE: In this article we confirm the analgesic effect of a combined neuromodulatory therapy, transcranial direct current stimulation associated with visual illusion in patients with NP after an SCI. We have identified 5 clusters of NP with distinct sensory phenotypes, but there was not any specific sensory phenotype cluster that significantly responded to the combined therapy better than the other.

Mental Imagery as a Rehabilitative Therapy for Neuropathic Pain in People With Spinal Cord Injury: A Randomized Controlled Trial.

BACKGROUND: Pain of neuropathic origin in spinal cord injury (SCI) is unbearable and challenging to treat. Research studies conducted in the past have shown that mental imagery (MI) techniques have a significant impact on the reduction of symptoms of central neuropathic pain in people with SCI. OBJECTIVES: The objective of this study was to evaluate the effect of MI training on pain intensity, neuropathic pain symptoms, and interference of pain with function in SCI. METHODS: A total of 42 SCI participants with central neuropathic pain (duration 6-12 months) were recruited and randomly allocated to MI or control groups. A MI training protocol was administered to MI group and for 30 min/d for 5 days. Outcome measures were assessed at baseline and at the end of 4 weeks. RESULTS: There was significant reduction in differences of mean [95% CI] scores of numeric rating scale (-2.1 [CI -2.78 to -1.41]; P < .001) between groups. Mean [95% CI] total scores of Neuropathic Pain Symptom Inventory declined in MI group as compared with control group (-4.52 [CI -5.86 to -3.18]; P < .001). Similarly, Brief Pain Inventory interference scale total dropped significantly (P < .001) in MI group. Majority of participants in the MI group (55%) reported improvement in scores of Patients' Global Impression of Change scale as compared with control group where most of the participants (52%) reported no change. CONCLUSIONS: This study shows the effectiveness of the MI protocol developed as a rehabilitative approach in improving central neuropathic pain in SCI. Trial Registration. Clinical Trials Registry-India under Indian Council of Medical Research; CTRI/2018/07/014884. Registered July 16, 2018.

A pragmatic randomized controlled trial testing the effects of the international scientific SCI exercise guidelines on SCI chronic pain: protocol for the EPIC-SCI trial.

STUDY DESIGN: Protocol for a pragmatic randomized controlled trial (the Exercise guideline Promotion and Implementation in Chronic SCI [EPIC-SCI] Trial). PRIMARY OBJECTIVES: To test if home-/community-based exercise, prescribed according to the international SCI exercise guidelines, significantly reduces chronic bodily pain in adults with SCI. SECONDARY OBJECTIVES: To investigate: (1) the effects of exercise on musculoskeletal and neuropathic chronic pain; (2) if reduced inflammation and increased descending inhibitory control are viable pathways by which exercise reduces pain; (3) the effects of chronic pain reductions on subjective well-being; and (4) efficiency of a home-/community-based exercise intervention. SETTING: Exercise in home-/community-based settings; assessments in university-based laboratories in British Columbia, Canada. METHOD: Eighty-four adults with chronic SCI, reporting chronic musculoskeletal or neuropathic pain, and not meeting the current SCI exercise guidelines, will be recruited and randomized to a 6-month Exercise or Wait-List Control condition. Exercise will occur in home/community settings and will be supported through behavioral counseling. All measures will be taken at baseline, 3-months and 6-months. Analyses will consist of linear mixed effect models, multiple regression analyses and a cost-utility analysis. The economic evaluation will examine the incremental costs and health benefits generated by the intervention compared with usual care. ETHICS AND DISSEMINATION: The University of British Columbia Clinical Research Ethics Board approved the protocol (#H19-01650). Using an integrated knowledge translation approach, stakeholders will be engaged throughout the trial and will co-create and disseminate evidence-based recommendations and messages regarding the use of exercise to manage SCI chronic pain.

Cold intolerance and neuropathic pain after peripheral nerve injury in upper extremity.

Cold intolerance and pain can be a substantial problem in patients with peripheral nerve injury. We aimed at investigating the relationships among sensory recovery, cold intolerance, and neuropathic pain in patients affected by upper limb peripheral nerve injury (Sunderland type V) treated with microsurgical repair, followed by early sensory re-education. In a cross-sectional clinical study, 100 patients (male/female 81/19; age 40.5 ± 14.8 years and follow-up 17 ± 5 months, mean ± SD), with microsurgical nerve repair and reconstruction in the upper extremity and subsequent early sensory re-education, were evaluated, using Cold Intolerance Symptoms Severity questionnaire-Italian version (CISS-it, cut-off pathology >30/100 points), CISS questionnaire-12 item version (CISS-12, 0-46 points-grouping: healthy that means no cold intolerance [0-14], mild [15-24], moderate [25-34], severe [35-42], very severe [43-46] cold intolerance), probability of neuropathic pain (DouleurNeuropathique-4; [DN4] 4/10), deep and superficial sensibility, tactile threshold (monofilaments), and two-point discrimination (cutoff S2; Medical Research Council scale for sensory function; [MRC-scale]). A high CISS score is associated with possible neuropathic pain (DN4 ≥ 4). Both a low CISS-it score (ie, < 30) and DN4 < 4 is associated with good sensory recovery (MRC ≥ 2). In conclusion patients affected by upper limb peripheral nerve injuries with higher CISS scores more often suffer from cold intolerance and neuropathic pain, and the better their sensory recovery is, the less likely they are to suffer from cold intolerance and neuropathic pain.

An Exploratory Randomized Trial of Physical Therapy for the Treatment of Chemotherapy-Induced Peripheral Neuropathy.

Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxane treatment and cannot currently be prevented or adequately treated. Physical therapy is often used for neural rehabilitation following injury but has not been evaluated in this patient population. Methods. Single-blind, randomized controlled exploratory study compared standard care to a physical therapy home program (4 visits) throughout adjuvant taxane chemotherapy for stage I-III patients with breast cancer (n = 48). Patient questionnaires and quantitative sensory testing evaluated the treatment effect throughout chemotherapy to 6 months post treatment. Nonrandomized subgroup analysis observed effect of general exercise on sensory preservation comparing those reporting moderate exercise throughout chemotherapy to those that did not exercise regularly. Clinical Trial Registration. clinicaltrials.gov (NCT02239601). Results. The treatment group showed strong trends toward less pain (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17-1.01; P = .053) and pain decreased over time (OR 0.85, 95% CI 0.76-0.94; P = .002). Pain pressure thresholds (P = .034) and grip dynamometry (P < .001) were improved in the treatment group. For the nonrandomized subgroup analysis, participants reporting general exercise had preservation of vibration (Left P = .001, Right P = .001) and normal heat pain thresholds (Left P = .021, Right P = .039) compared with more sedentary participants. Conclusion. Physical therapy home program may improve CIPN pain in the upper extremity for patients with breast cancer, and general exercise throughout chemotherapy treatment was observed to have correlated to preservation of sensory function. Further research is required to confirm the impact of a physical therapy home program on CIPN symptoms.

Neuropathic pain after spinal cord injury and physical exercise in animal models: A systematic review and meta-analysis.

The aim of this systematic review was to summarize the effects of physical exercise on neuropathic pain (NP) in animal models of SCI. The search was conducted in Medline and Science Direct to identify experimental preclinical studies involving animal models of SCI, physical exercise as an intervention and the assessment of NP. Fifteen articles met the eligibility criteria. The review shows that in studies of NP involving animal models of SCI, rodents are the most common species. Thoracic contusion is the most common injury and mechanical and thermal nociception are the most frequently assessed NP components. The benefits of physical exercise vary according to its starting period and total duration. In addition, there is considerable heterogeneity regarding the type and intensity of exercise capable of alleviating NP after SCI. Furthermore, physical exercise has beneficial effects on mechanical, thermal and cold nociception, and spontaneous pain. These results are weakened by the paucity of studies involving these pain outcomes. The review protocol is published for free access on the SyRF platform (http://syrf.org.uk/protocols/).

[Management of peripheral neuropathy in general internal medicine]. / Prise en charge des neuropathies périphériques en médecine interne générale.

Peripheral neuropathies are frequent in clinical practice and portend severe functional limitations or neuropathic pain. History taking and clinical examination represent key features to trigger investigations and uncover the underlying affection. For general internal medicine practitioners, initial investigation should include search for alcohol consumption, diabetes mellitus, vitamin B12 deficiency and monoclonal gammapathy. Nerve conduction studies should be limited to patients with atypical presentations and/or without a defined etiology. After treatment of specific etiologies, supportive care includes management of neuropathic pain and physical rehabilitation.

Les neuropathies périphériques sont fréquentes en pratique clinique, avec parfois une limitation fonctionnelle importante ou l'apparition de douleurs. L'anamnèse et l'examen clinique constituent des éléments importants pour établir un plan d'investigation et orienter le diagnostic. Pour l'interniste généraliste, la prise en charge initiale consiste à rechercher la présence d'une consommation d'alcool à risque, d'un diabète, d'un déficit en vitamine B12 ou d'une gammapathie monoclonale. Une étude de la conduction nerveuse est réservée aux présentations atypiques et/ou sans cause claire. Hormis le traitement des étiologies réversibles, le soutien au patient passe par la gestion des douleurs neuropathiques et par une prise en charge rééducative.

Virtual reality for spinal cord injury-associated neuropathic pain: Systematic review.

BACKGROUND: Treatment of spinal cord injury (SCI)-associated neuropathic pain is challenging, with limited efficacy and no definitive options, and SCI patients often show resistance to pharmacologic treatment. Virtual reality (VR) therapy is a non-invasive, non-pharmacologic alternative with minimal adverse effects. OBJECTIVE: To investigate the effect of VR therapy on SCI-associated neuropathic pain in a systematic review. METHODS: Articles needed to 1) be written in English; 2) include adult subjects, with at least half the study population with a SCI diagnosis; 3) involve any form of VR therapy; and 4) assess neuropathic pain by quantitative outcome measures. Articles were searched in MEDLINE/PubMed, CINAHL®, EMBASE, and PsycINFO up to April 2018. Reference lists of retrieved articles were hand-searched. Methodologic quality was assessed by the Physiotherapy Evidence Database Score (PEDro) for randomized controlled trials and Modified Downs and Black Tool (D&B) for all other studies. Level of evidence was determined by using a modified Sackett scale. RESULTS: Among 333 studies identified, 9 included in this review (n=150 participants) evaluated 4 methods of VR therapy (virtual walking, VR-augmented training, virtual illusion, and VR hypnosis) for treating neuropathic pain in SCI patients. Each VR method reduced neuropathic pain: 4 studies supported virtual walking, and the other 3 VR methods were each supported by a different study. Combined treatment with virtual walking and transcranial direct current stimulation was the most effective. The quality of studies was a major limitation. CONCLUSION: VR therapy could reduce SCI-associated neuropathic pain, although the clinical significance of this analgesic effect is unclear. Clinical trials evaluating VR therapy as standalone and/or adjunct therapy for neuropathic pain in SCI patients are warranted.

Effects of virtual walking on spinal cord injury-related neuropathic pain: A randomized, controlled trial.

PURPOSE: This study is an examination of the efficacy of a virtual walking protocol to treat spinal cord injury (SCI)-related pain. METHOD: A total of 59 individuals with SCI and neuropathic pain (NP) were randomly assigned to receive 20 min of virtual walking, the treatment condition, or virtual wheeling, the control condition. Although having NP was a requirement to participate in the study, participants also underwent pain classification of up to 3 worst pain sites to also examine the effects of virtual walking on nonneuropathic pain. Pain outcomes included changes in pain severity across all pain types, NP unpleasantness, and severity of various sensory qualities of NP. DESIGN: This was a randomized, controlled, single-blinded trial. RESULTS: There was no significant difference in change in pain between groups, though there was a significant pre- to posttreatment reduction across all pain types in the virtual walking condition, but not the control condition. Specific to NP, there was a significant reduction in pain unpleasantness, but not neuropathic pain intensity. NP experienced as "cold," "deep," and with increased skin sensitivity were significantly reduced following virtual walking compared with the control condition. CONCLUSION: Results from this trial suggest that virtual walking treatment may benefit certain aspects of NP, such as associated unpleasantness, as well as certain sensory qualities of that pain. Efficacy of this treatment modality to reduce overall pain severity remains unclear, and may be modulated by other injury, individual, or personality characteristics. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Managing limb pain using virtual reality: a systematic review of clinical and experimental studies.

Purpose: The aim of this systematic review was to assess the effect of virtual representation of body parts on pain perception in patients with pain and in pain-free participants exposed to experimentally induced pain.Methods: Databases searched: Medline, PsycInfo, CINAHL, and Web of Science. Studies investigating participants with clinical pain or those who were pain free and exposed to experimentally induced pain were analysed separately.Results: Eighteen clinical studies and seven experimental studies were included. Randomised controlled clinical trials showed no significant difference between intervention and control groups for pain intensity. Clinical studies with a single group pretest-posttest design showed a reduction in pain after intervention. In the studies including a sample of pain free participants exposed to experimentally induced pain there was an increase in pain threshold when the virtual arm was collocated with the real arm, when it moved in synchrony with the real arm, and when the colour of the stimulated part of the virtual arm became blue. Observing a virtual arm covered with iron armour reduced pain.Conclusions: The use of virtual representations of body parts to reduce pain is promising. However, due to the poor methodological quality and limitations of primary studies, we could not find conclusive evidence.Implications for rehabilitationVirtual reality has been increasingly used in the rehabilitation of painful and dysfunctional limbs.Virtual reality can be used to distract attention away from acute pain and may also provide corrective psychological and physiological environments.Virtual representation of body parts has been used to provide a corrective re-embodiment of painful dysmorphic body parts, and primary research shows promising results.

Gestural Interaction and Visual Illusion for Lower Limbs' Neuropathic Pain Treatment.

Pain caused by a lesion or a disease affecting the somatosensory nervous system is known as Neuropathic pain. It has been shown that neuropathic pain can be treated with the combination of simultaneous transcranial direct current stimulation and the generation of the visual illusion that the patient retains control of the affected limbs. For persons with neuropathic pain in the lower limbs, the visual illusion consists of an image of the patient walking normally. Such a visual illusion has classically been generated by using a physical mirror and a projector. The objective of this paper is to develop and validate a computer-based version of the visual illusion, including Gestural Control. The developed system has been validated in a trial and has been successfully implanted in daily clinical practice in a reference neurorehabilitation hospital. A retrospective statistical analysis shows that the patients treated with the computer-based system reduce their pain level significantly more than the patients treated with the mirror and projector treatment before the introduction of the computer-based version. Furthermore, it also makes possible to bring the therapy to the home of the patients, where the treatment can be self-administered while still being monitored by the clinical staff.

Non-pharmacological treatment affects neuropeptide expression in neuropathic pain model.

Chronic constriction injury (CCI) of the sciatic nerve elicits changes in neuropeptide expression on the dorsal root ganglia (DRG). The neural mobilization (NM) technique is a noninvasive method that has been proven clinically effective in reducing pain. The aim of this study was to analyze the expression of substance P, transient receptor potential vanilloid 1 (TRPV1) and opioid receptors in the DRG of rats with chronic constriction injury and to compare it to animals that received NM treatment. CCI was performed on adult male rats. Each animal was submitted to 10 sessions of neural mobilization every other day, starting 14 days after the CCI injury. At the end of the sessions, the DRG (L4-L6) were analyzed using Western blot assays for substance P, TRPV1 and opioid receptors (µ-opioid receptor, δ-opioid receptor and κ-opioid receptor). We observed a decreased substance P and TRPV1 expression (48% and 35%, respectively) and an important increase of µ-opioid receptor expression (200%) in the DRG after NM treatment compared to control animals. The data provide evidence that NM promotes substantial changes in neuropeptide expression in the DRG; these results may provide new options for treating neuropathic pain.

Cold forced open-water swimming: a natural intervention to improve postoperative pain and mobilisation outcomes?

Postoperative neuropathic pain exacerbated by movement is poorly understood and difficult to treat but a relatively common complication of surgical procedures such as endoscopic thoracic sympathectomy. Here, we describe a case of unexpected, immediate, complete and sustained remission of postoperative intercostal neuralgia after the patient engaged in an open-water swim in markedly cold conditions. Though an incidental chance association is possible, the clear temporal proximity linking the swim with pain remission makes a causal relationship possible. We discuss plausible mechanisms that may underlie the relationship and discuss the potential implications for postoperative pain management and patient-centred mobilisation. We recommend further evaluation of cold forced open-water swimming as a mobility-pain provocation challenge to see if the observed unexpectedly positive outcome can be replicated. With the poor response to traditional management, there is a need for novel, curative interventions for postoperative neuropathic pain and associated impaired mobility.

Guía de la Academia Europea de Neurología sobre terapia de neuroestimulación central en condiciones de dolor crónico / European Academy of Neurology guidelines on central neurostimulation therapy in chronic pain conditions

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Transplantation of olfactory ensheathing cells on functional recovery and neuropathic pain after spinal cord injury; systematic review and meta-analysis.

There are considerable disagreements on the application of olfactory ensheathing cells (OEC) for spinal cord injury (SCI) rehabilitation. The present meta-analysis was designed to investigate the efficacy of OEC transplantation on motor function recovery and neuropathic pain alleviation in SCI animal models. Accordingly, all related studies were identified and included. Two independent researchers assessed the quality of the articles and summarized them by calculating standardized mean differences (SMD). OEC transplantation was shown to significantly improve functional recovery (SMD = 1.36; 95% confidence interval: 1.05-1.68; p < 0.001). The efficacy of this method was higher in thoracic injuries (SMD = 1.41; 95% confidence interval: 1.08-1.74; p < 0.001) and allogeneic transplants (SMD = 1.53; 95% confidence interval: 1.15-1.90; p < 0.001). OEC transplantation had no considerable effects on the improvement of hyperalgesia (SMD = -0.095; 95% confidence interval: -0.42-0.23; p = 0.57) but when the analyses were limited to studies with follow-up ≥8 weeks, it was associated with increased hyperalgesia (SMD = -0.66; 95% confidence interval: -1.28-0.04; p = 0.04). OEC transplantation did not affect SCI-induced allodynia (SMD = 0.54; 95% confidence interval: -0.80-1.87; p = 0.43). Our findings showed that OEC transplantation can significantly improve motor function post-SCI, but it has no effect on allodynia and might lead to relative aggravation of hyperalgesia.