Tactile Thresholds are Preserved yet Cortical Sensory Function is Impaired in Chronic Non-Specific Low Back Pain Patients

Introduction: A substantial amount of evidence points to an alteration in brain structure and function patients with chronic non-specific low back pain (CNSLBP) [1-6]. One interpretation of these findings is that the observed brain changes may represent a disruption of the brain’s representations of the body part and the resultant body perception disturbance may underpin this clinical problem. The current study aimed to investigate sensory dysfunction in CNSLBP. Specifically we aimed to distinguish cortically mediated sensory dysfunction from peripheral dysfunction by comparing simple tactile thresholds with more complex cortically mediated sensory tests Methods: We investigated tactile thresholds (TTH), two point discrimination (TPD) and graphaesthesia over the lumbar spine of 19 CLBP patients and 19 age and sex matched healthy controls as a way of investigating whether CLBP patients present with a perceptual disturbance of their lumbar spine. Differences in performance of the sensory tests was explored using the Mann Whitney U Test and one-way between groups multivariate analysis of variance. Results: We found no difference in tactile threshold between the two groups (P=.0.751). There was a statistically significant difference between controls and LBP for TPD: F(1,36)=10.15, p=.003 and letter error rate: F(1, 36)=6.54 p=0.015. The data indicate that LBP patients had a larger lumbar TPD distance and a greater letter recognition error rate. Discussion: Both TPD and graphaesthesia are dependant on the integrity of the primary sensory cortex [7]. These data support existing findings of perceptual abnormality in chronic back pain [8] and the preservation of tactile thresholds is suggestive of cortical rather than peripheral sensory dysfunction. Amelioration of these abnormalities may present a target for therapeutic intervention

Self reported aggravating activities do not demonstrate a consistent directional pattern in chronic non specific low back pain patients: An observational study

Question: Do the self-reported aggravating activities of chronic non-specific low back pain patients demonstrate a consistent directional pattern? Design: Cross-sectional observational study. Participants: 240 chronic non specific low back pain patients. Outcome measure: We invited experienced clinicians to classify each of the three self-nominated aggravating activities from the Patient Specific Functional Scale by the direction of lumbar spine movement. Patients were described as demonstrating a directional pattern if all nominated activities moved the spine into the same direction. Analyses were undertaken to determine if the proportion of patients demonstrating a directional pattern was greater than would be expected by chance. Results: In some patients, all tasks did move the spine into the same direction, but this proportion did not differ from chance (p = 0.328). There were no clinical or demographic differences between those who displayed a directional pattern and those who did not (all p > 0.05). Conclusion: Using patient self-reported aggravating activities we were unable to demonstrate the existence of a consistent pattern of adverse movement in patients with chronic non-specific low back pain

Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II (Review)

Background: Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery. When it occurs, it is associated with significant pain and disability. It is thought to arise and persist as a consequence of a maladaptive pro-inflammatory response and disturbances in sympathetically-mediated vasomotor control, together with maladaptive peripheral and central neuronal plasticity. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified, and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS, although their effectiveness is not known. Objectives: To determine the effectiveness of physiotherapy interventions for treating the pain and disability associated with CRPS types I and II. Search methods: We searched the following databases from inception up to 12 February 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments, without language restrictions, for randomised controlled trials (RCTs) of physiotherapy interventions for treating pain and disability in people CRPS. We also searched additional online sources for unpublished trials and trials in progress. Selection criteria: We included RCTs of physiotherapy interventions (including manual therapy, therapeutic exercise, electrotherapy, physiotherapist administered education and cortically directed sensory-motor rehabilitation strategies) employed in either a stand-alone fashion or in combination, compared with placebo, no treatment, another intervention or usual care, or of varying physiotherapy interventions compared with each other in adults with CRPS I and II. Our primary outcomes of interest were patient-centred outcomes of pain intensity and functional disability. Data collection and analysis: Two review authors independently evaluated those studies identified through the electronic searches for eligibility and subsequently extracted all relevant data from the included RCTs. Two review authors independently performed ’Risk of bias’ assessments and rated the quality of the body of evidence for the main outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results: We included 18 RCTs (739 participants) that tested the effectiveness of a broad range of physiotherapy-based interventions. Overall, there was a paucity of high quality evidence concerning physiotherapy treatment for pain and disability in people with CRPS I. Most included trials were at ’high’ risk of bias (15 trials) and the remainder were at ’unclear’ risk of bias (three trials). The quality of the evidence was very low or low for all comparisons, according to the GRADE approach. We found very low quality evidence that graded motor imagery (GMI; two trials, 49 participants) may be useful for improving pain (0 to 100 VAS) (mean difference (MD) −21.00, 95% CI −31.17 to −10.83) and functional disability (11-point numerical rating scale) (MD 2.30, 95% CI 1.12 to 3.48), at long-term (six months) follow-up, in people with CRPS I compared to usual care plus physiotherapy; very low quality evidence that multimodal physiotherapy (one trial, 135 participants) may be useful for improving ’impairment’ at long-term (12 month) follow-up compared to a minimal ’social work’ intervention; and very low quality evidence that mirror therapy (two trials, 72 participants) provides clinically meaningful improvements in pain (0 to 10 VAS) (MD 3.4, 95% CI −4.71 to −2.09) and function (0 to 5 functional ability subscale of the Wolf Motor Function Test) (MD −2.3, 95% CI −2.88 to −1.72) at long-term (six month) follow-up in people with CRPS I post stroke compared to placebo (covered mirror). There was low to very low quality evidence that tactile discrimination training, stellate ganglion block via ultrasound and pulsed electromagnetic field therapy compared to placebo, and manual lymphatic drainage combined with and compared to either anti-inflammatories and physical therapy or exercise are not effective for treating pain in the short-termin people with CRPS I. Laser therapy may provide small clinically insignificant, short-term, improvements in pain compared to interferential current therapy in people with CRPS I. Adverse events were only rarely reported in the included trials. No trials including participants with CRPS II met the inclusion criteria of this review. Authors’ conclusions: The best available data show that GMI and mirror therapy may provide clinically meaningful improvements in pain and function in people with CRPS I although the quality of the supporting evidence is very low. Evidence of the effectiveness of multimodal physiotherapy, electrotherapy and manual lymphatic drainage for treating people with CRPS types I and II is generally absent or unclear. Large scale, high quality RCTs are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability of people with CRPS I and II. Implications for clinical practice and future research are considered

Sequential Data-Adaptive Bandwidth Selection by Cross-Validation for Nonparametric Prediction

We consider the problem of bandwidth selection by cross-validation from a sequential point of view in a nonparametric regression model. Having in mind that in applications one often aims at estimation, prediction and change detection simultaneously, we investigate that approach for sequential kernel smoothers in order to base these tasks on a single statistic. We provide uniform weak laws of large numbers and weak consistency results for the cross-validated bandwidth. Extensions to weakly dependent error terms are discussed as well. The errors may be {\alpha}-mixing or L2-near epoch dependent, which guarantees that the uniform convergence of the cross validation sum and the consistency of the cross-validated bandwidth hold true for a large class of time series. The method is illustrated by analyzing photovoltaic data.Comment: 26 page

Rethinking clinical trials of transcranial direct current stimulation: Participant and assessor blinding is inadequate at intensities of 2mA

Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.Background: Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding. Methods: A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation. Results: tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding. Conclusions: Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.GLM is supported by the National Health & Medical Research Council of Australia ID 571090

Transcutaneous Electrical Nerve Stimulation (TENS) for chronic pain - an overview of Cochrane reviews (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To provide an overview of evidence from Cochrane systematic reviews of the effectiveness of TENS to reduce pain in adults with chronic pain (excluding headache or migraine). To provide an overview of evidence from Cochrane systematic reviews of the safety of TENS to reduce pain in adults with chronic pain (excluding headache or migraine). To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency. To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine) with a view to recommending strategies to reduce any uncertainty

Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation

Evidence indicates that chronic non-specific low back pain (CNSLBP) is associated with alteration in the brain’s cortical representation of the back, resulting in body perception disturbance and contributing to the condition [1,2]. This study investigated perception via ‘cortical’ sensory tests, in this case two-point discrimination and graphaesthesia—whose results partly depend on the integrity of cortical representation [2]. The hypothesis was dysfunction in these higher-order tasks, with simple tactile thresholds remaining unchanged. Furthermore a relationship between cortical sensation and severity of the condition was predicted

Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis

addresses: Biosciences, College of Life and Environmental Sciences, Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter, Devon, EX4 4QD, UK.notes: PMCID: PMC3025829types: Journal Article; Research Support, Non-U.S. Gov't© 2011 Wand et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. In murine models of infection, different strains exhibit varying degrees of virulence. In contrast, two related species, B. thailandensis and B. oklahomensis, are highly attenuated in mice. Our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (Galleria mellonella) infection models

Non-invasive brain stimulation techniques for chronic pain (Review)

Background: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). Objectives: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. Search methods: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. Selection criteria: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months’ duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. Data collection and analysis: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three ’Summary of findings’ tables. Main results: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision. rTMS: Meta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to \u3c 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence). CES: For CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence). tDCS: Analysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence). Adverse events: All forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. Authors’ conclusions: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results