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The Effect of Non-invasive Brain Stimulation to Reduce Non-specific Low Back Pain: A Systematic Review and Meta-analysis
Abstract
Objective: We conducted a systematic review/meta-analysis to evaluate NIBS efficacy to alleviate pain and improve disability in LBP.
Methods: A systematic literature search was performed by a librarian in MEDLINE, Embase, EBM Reviews, CINAHL and Web of Science databases (last search : January 14th, 2021). Data were pooled by number of sessions and follow-up periods. Independent reviewers performed screening, data extraction and risk of bias. Pain reduction and disability were used as outcomes.
Results: Twelve articles were included in the qualitative synthesis and eight in the meta-analysis. A single session of NIBS reduced pain compared to sham (standardized mean difference: −0.47; P<0.001 | very low-quality evidence). Repeated sessions of NIBS did not impact pain at short-term (mean difference (MD): −0.31; P=0.23) or mid-term (MD: −0.56; P=0.33 | moderate quality evidence). Combining NIBS with co-interventions did not influence pain (MD: −0.31; P=0.30 | moderate quality evidence). NIBS did not influence disability.
Discussion: There is very low-quality evidence suggesting that a single NIBS session reduces LBP intensity. In contrast, there is moderate quality evidence that repeated NIBS sessions or combination with co-intervention did not improve pain or disability. Thus, current results do not support NIBS use to treat CLBP. Considering that tDCS was tested in eight out of twelve studies with little success, studies focusing on different NIBS techniques or innovative parameters are required to determine their potential to improve pain and disability in CLBP.
... These results are the first to suggest a different organization in motor spinal networks in humans and add to the evidence of altered central nervous system motor pathways [6][7][8][9][10]64,65]. Also, it is suggested that M1 may contribute to the top-down control of nociception and pain processing (see references [66,67]), and it could in part explain differences observed in NWR in CLBP. Differences in the organization of spinal networks controlling trunk muscles are likely to contribute to the alteration in spine motor control in CLBP [3,61,68] in conjunction with changes in supraspinal areas [13]. ...
Individuals with chronic low back pain (CLBP) move their spine differently. Changes in brain motor areas have been observed and suggested as a mechanism underlying spine movement alteration. Nociceptive withdrawal reflex (NWR) might be used to test spinal networks involved in trunk protection and to highlight reorganization. This study aimed to determine whether the organization and excitability of the trunk NWR are modified in CLBP. We hypothesized that individuals with CLBP would have modified NWR patterns and lower NWR thresholds. Noxious electrical stimuli were delivered over S1, L3 and T12, and the 8th Rib to elicit NWR in 12 individuals with and 13 individuals without CLBP. EMG amplitude and occurrence of lumbar multifidus (LM), thoracic erector spinae, rectus abdominus, obliquus internus and obliquus externus motor responses were recorded using surface electrodes. Two different patterns of responses to noxious stimuli were identified in CLBP compared to controls: (i) abdominal muscle NWR responses were generally more frequent following 8th rib stimulation and (ii) occurrence of erector spinae NWR was less frequent. In addition, we observed a subgroup of participants with very high NWR threshold in conjunction with the larger abdominal muscle responses. These results suggest sensitization of NWR is not present in all individuals with CLBP, and a modified organization in the spinal networks controlling the trunk muscles that might explain some changes in spine motor control observed in CLBP.
... Although a recent systematic review reported no effect of M1 rTMS in the treatment of chronic low back pain, these findings were based upon only one small study (n = 10) that is yet to be replicated (Patricio et al., 2021). Further research is required to determine whether the effects observed following M1 rTMS in neuropathic pain translate to musculoskeletal pain and other chronic pain conditions. ...
The overarching aim of this thesis was to enhance our understanding of early corticomotor reorganisation in response to novel stimuli (motor skill training and acute pain). To achieve this aim, four primary studies (Chapters 2-5) were conducted and published. Study 1 (Chapter 2) explored the within- and between-session reliability of corticomotor outcomes assessed using rapid TMS mapping (map area, volume, centre of gravity, discrete peaks in corticomotor excitability, and mean motor evoked potential). This study also assessed the validity of rapid mapping by testing its equivalence with traditional mapping methods. Study 2 (Chapter 3) used rapid mapping to investigate corticomotor reorganisation during short-term motor skill learning in thirty individuals. This study demonstrated, for the first time, that reorganisation of lower back muscle representations occurs rapidly (within minutes) in certain individuals. Study 3 (Chapter 4) explored the temporal profile and variability of corticomotor reorganisation in response to acute experimental pain. Findings of this study suggest that early corticomotor responses could be used as an index to predict symptom severity. This could have utility in stratifying individuals according to their likelihood of increased or persistent pain and the development of targeted management strategies. Study 4 (Chapter 5) investigated this possibility using repeated intramuscular injection of nerve growth factor, a novel and clinically-relevant model of musculoskeletal pain. The findings of this study suggest that early rTMS over M1 may expedite recovery following acute musculoskeletal pain or injury. Taken together, this thesis makes a substantial and original contribution to our understanding of neuroplasticity. By evaluating rapid TMS mapping, early corticomotor reorganisation can now be assessed validly and reliably, allowing exploration of early drivers of nervous system plasticity. Decreasing map acquisition times may also increase the utility of TMS beyond research settings, potentially allowing corticomotor reorganisation to be assessed in clinical environments. The experimental studies throughout this thesis provide valuable insight into the temporal profile and modifiability of early corticomotor reorganisation. This work highlights the prognostic and therapeutic utility of exploring early corticomotor reorganisation and the need for further research in this area.
... The maximal score that corresponds with a minimal risk of bias is 28. Articles with scores >20 are considered strong, 14-20 moderate, 7-13 limited and <7 poor [28]. ...
Background:
Work-related musculoskeletal disorders (WRMSDs) remain a challenge despite research aimed at improving their prevention and treatment. Extrinsic feedback has been suggested for the prevention and rehabilitation of WRMSDs to improve sensorimotor control, and ultimately to reduce pain and disability. However, there are few systematic reviews on the effectiveness of extrinsic feedback for WRMSDs.
Objective:
To perform a systematic review investigating the effect of extrinsic feedback for the prevention and rehabilitation of WRMSDs.
Methods:
Five databases (CINAHL, Embase, Ergonomics Abstract, PsycInfo, PubMed) were searched. Studies of various designs assessing the effects of extrinsic feedback during work tasks on three outcomes (function, symptoms, sensorimotor control) in the context of prevention and rehabilitation of WRMSDs were included.
Results:
Forty-nine studies were included, for a total sample of 3387 participants (including 925 injured) who performed work-related tasks in the workplace (27 studies) or in controlled environments (22 studies). The use of extrinsic feedback was shown to be effective in controlled environments for short-term prevention of functional limitations and sensorimotor alterations (very limited to moderate evidence) and for improving, in injured participants, function, symptoms and sensorimotor control (moderate evidence). In the workplace, it was shown to be effective for short-term prevention of functional limitations (limited evidence). There was conflicting evidence regarding its effect for WRMSD rehabilitation in the workplace.
Conclusion:
Extrinsic feedback is an interesting complementary tool for the prevention and rehabilitation of WRMSDs in controlled environments. More evidence is needed regarding its effect for the prevention and rehabilitation of WRMSDs in the workplace.
... 45 46 A recent meta-analysis demonstrates that there is moderate quality evidence suggesting that neither repeated sessions of non-invasive brain stimulation nor its combination with other treatments significantly improves pain or disability in people with CLBP. 45 As most studies evaluating tDCS of single brain region demonstrated little success in improving pain and disability in people with CLBP, future trials focusing on different TES techniques, targeting multiple cortical areas, using various parameters are warranted and recommended. The proposed research will be the first randomised placebo-controlled pilot study Open access to explore a novel HD-tIPNS technique targeting multiple brain regions simultaneously in individuals with CLBP. ...
Introduction
Chronic low back pain (CLBP) is a common disabling health condition. Current treatments demonstrate modest effects, warranting newer therapies. Brain imaging demonstrates altered electrical activities in cortical areas responsible for pain modulation, emotional and sensory components of pain experience. Treatments targeting to change electrical activities of these key brain regions may produce clinical benefits. This pilot study aims to (1) evaluate feasibility, safety and acceptability of a novel neuromodulation technique, high-definition transcranial infraslow pink noise stimulation (HD-tIPNS), in people with CLBP, (2) explore the trend of effect of HD-tIPNS on pain and function, and (3) derive treatment estimates to support sample size calculation for a fully powered trial should trends of effectiveness be present.
Methods and analysis
A pilot, triple-blinded randomised two-arm placebo-controlled parallel trial. Participants (n=40) with CLBP will be randomised to either sham stimulation or HD-tIPNS (targeting somatosensory cortex and dorsal and pregenual anterior cingulate cortex). Primary outcomes include feasibility and safety measures, and clinical outcomes of pain (Brief Pain Inventory) and disability (Roland-Morris disability questionnaire). Secondary measures include clinical, psychological, quantitative sensory testing and electroencephalography collected at baseline, immediately postintervention, and at 1-week, 1-month and 3 months postintervention. All data will be analysed descriptively. A nested qualitative study will assess participants perceptions about acceptability of intervention and analysed thematically.
Ethics and dissemination
Ethical approval has been obtained from Health and Disability Ethics Committee (Ref:20/NTB/67). Findings will be reported to regulatory and funding bodies, presented at conferences, and published in a scientific journal.
Trial registration number
ACTRN12620000505909p.
... Therefore, brain network disturbance is considered one of the possible causes of CLBP. A recent systematic analysis (eight studies) revealed that, compared with sham stimulation, 1 session of tDCS treatment resulted in substantial pain relief (Patricio et al., 2021). By contrast, multiple sessions of tDCS treatment did not improve short-term and medium-term pain. ...
As a technique that can guide brain plasticity, non-invasive brain stimulation (NIBS) has the potential to improve the treatment of chronic pain (CP) because it can interfere with ongoing brain neural activity to regulate specific neural networks related to pain management. Treatments of CP with various forms of NIBS, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), using new parameters of stimulation have achieved encouraging results. Evidence of moderate quality indicates that high-frequency rTMS of the primary motor cortex has a clear effect on neuropathic pain (NP) and fibromyalgia. However, evidence on its effectiveness regarding pain relief in other CP conditions is conflicting. Concerning tDCS, evidence of low quality supports its benefit for CP treatment. However, evidence suggesting that it exerts a small treatment effect on NP and headaches is also conflicting. In this paper, we describe the underlying principles behind these commonly used stimulation techniques; and summarize the results of randomized controlled trials, systematic reviews, and meta-analyses. Future research should focus on a better evaluation of the short-term and long-term effectiveness of all NIBS techniques and whether they decrease healthcare use, as well as on the refinement of selection criteria.
Structural and functional changes of the brain occur in many chronic pain conditions, including chronic low back pain (CLBP), and these brain abnormalities can be reversed by effective treatment. Research on the clinical applications of non-invasive brain neuromodulation (NIBS) techniques for chronic pain is increasing. Unfortunately, little is known about the effectiveness of NIBS on CLBP, which limits its application in clinical pain management. Therefore, we summarized the effectiveness and limitations of NIBS techniques on CLBP management and described the effects and mechanisms of NIBS approaches on CLBP in this review. Overall, NIBS may be effective for the treatment of CLBP. And the analgesic mechanisms of NIBS for CLBP may involve the regulation of pain signal pathway, synaptic plasticity, neuroprotective effect, neuroinflammation modulation, and variations in cerebral blood flow and metabolism. Current NIBS studies for CLBP have limitations, such as small sample size, relative low quality of evidence, and lack of mechanistic studies. Further studies on the effect of NIBS are needed, especially randomized controlled trials with high quality and large sample size.
Purpose of review:
Chronic pain is debilitating and difficult to treat with pharmacotherapeutics alone. Consequently, exploring alternative treatment methods for chronic pain is essential. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are increasingly being investigated for their neuropharmacological effects in the treatment of chronic pain. This review aims to examine and evaluate the present state of evidence regarding the use of tDCS and TMS in the treatment of chronic pain.
Recent findings:
Despite conflicting evidence in the early literature, evidence from recent rigorous research supports the use of tDCS and TMS in treating chronic pain conditions. For both tDCS and TMS, standardized stimulation parameters have been identified with the recommendation for repeated maintenance stimulation to ensure that the analgesic effect is sustained beyond discontinuation of therapy.
Summary:
Due to a lack of defined stimulation protocols, early findings on the efficacy of tDCS and TMS are mixed. Although the application of tDCS and TMS as pain relief approaches is still in its early stages, the introduction of standardized stimulation protocols is paving the way for more robust and informed research.
Transcranial direct current stimulation (tDCS) has been used to reduce pain in range of chronic pain states. The aim of this review is to evaluate the effectiveness of tDCS on pain reduction and related disability in patients with non-specific chronic low back pain (CLBP). A computer-based systematic literature search was performed in five databases according to PRISMA guidelines. Randomized controlled trials (RCTs) that assessed the effects of tDCS on pain and related disability in patients with non-specific CLBP were included. Modified Jadad scale and Cochrane's risk of bias assessment were used to determine the studies’ quality and risk of bias. Meta-analyses were performed by calculating the standardized mean difference (SMD) at 95% confidence interval (CI). Nine RCTs (411 participants) were included in the systematic review according to inclusion criteria, while only five studies could be included in the meta-analysis. The primary motor cortex (M1) was the main stimulated target. The meta-analysis showed non-significant effect of multiple sessions of tDCS over M1 on pain reduction and disability post-treatment respectively, (SMD = 0.378; 95% CI = − 0.264–1.020; P = 0.249), (SMD = 0.143; 95% CI = − 0.214–0.499; P = 0.434). No significant adverse events were reported. The current results do not support the clinical use of tDCS for the reduction of pain and related disability in non-specific CLBP. However, the limited number of available evidence limits our conclusions on the effectiveness of these approaches.
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.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 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).CESFor 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).tDCSAnalysis 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 eventsAll 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.
Background
The prevalence of chronic pain and sleep disturbances substantially increases with age. Pharmacotherapy remains the primary treatment option for these health issues. However, side effects and drug interactions are difficult to control in elderly individuals.
Aims
The objective of this study was to assess the feasibility of conducting a randomized sham-controlled trial and to collect preliminary data on the efficacy of transcranial direct current stimulation (tDCS) to reduce pain and improve sleep in older adults suffering from chronic pain.
Methods
Fourteen elderly individuals (mean age 71±7 years) suffering from chronic pain and sleep complaints were randomized to receive either anodal tDCS, applied over the primary motor cortex (2 mA, 20 minutes), or sham tDCS, for 5 consecutive days. Pain was measured with visual analog scales, pain logbooks and questionnaires, while sleep was assessed with actigraphy, sleep diaries and questionnaires.
Results
There were no missing data for pain and sleep measures, except for actigraphy, that generated several missing data. Blinding was maintained throughout the study, for both the evaluator and participants. Active but not sham tDCS significantly reduced pain (P<0.05). No change was observed in sleep parameters, in both the active and sham tDCS groups (all P≥0.18).
Conclusion
The present study provides guidelines for the implementation of future tDCS studies in larger populations of elderly individuals. M1 anodal tDCS in this population appears to be effective to reduce pain, but not to improve sleep.
The aim was to critically evaluate the literature investigating strength training interventions in the treatment of plantar fasciitis and improving intrinsic foot musculature strength.
A search of PubMed, CINHAL, Web of Science, SPORTSDiscus, EBSCO Academic Search Complete and PEDRO using the search terms plantar fasciitis, strength, strengthening, resistance training, intrinsic flexor foot, resistance training.
Seven articles met the eligibility criteria. Methodological quality was assessed using the modified Downs and Black checklist. All articles showed moderate to high quality, however external validity was low.
A comparison of the interventions highlights significant differences in strength training approaches to treating plantar fasciitis and improving intrinsic strength. It was not possible to identify the extent to which strengthening interventions for intrinsic musculature may benefit symptomatic or at risk populations to plantar fasciitis. There is limited external validity that foot exercises, toe flexion against resistance and minimalist running shoes may contribute to improved intrinsic foot musculature function. Despite no plantar fascia thickness changes being observed through high-load plantar fascia resistance training there are indications that it may aid in a reduction of pain and improvements in function.
Further research should use standardised outcome measures to assess intrinsic foot musculature strength and plantar fasciitis symptoms.
[1st paragraph] When conducting exhaustive searches for systematic reviews, information professionals search multiple databases with overlapping content. They typically remove duplicate records to reduce the reviewers’ workload associated with screening titles and abstracts; sometimes the reviewers remove the duplicates. Several articles have been published recently on de-duplication methods. In the authors’ opinion, these methods are either very time consuming or impractical, as they require uploading large files to an online platform. A recent overview article compared existing software programs but found that none was truly satisfactory.
Low back pain (LBP) is a heterogeneous disorder including patients with dominant nociceptive (e.g., myofascial low back pain), neuropathic (e.g., lumbar radiculopathy), and central sensitization pain. In order to select an effective and preferably also efficient treatment in daily clinical practice, LBP patients should be classified clinically as either predominantly nociceptive, neuropathic, or central sensitization pain.
To explain how clinicians can differentiate between nociceptive, neuropathic, and central sensitization pain in patients with LBP.
Narrative review and expert opinion SETTING: Universities, university hospitals and private practices METHODS: Recently, a clinical method for the classification of central sensitization pain versus neuropathic and nociceptive pain was developed. It is based on a body of evidence of original research papers and expert opinion of 18 pain experts from 7 different countries. Here we apply this classification algorithm to the LBP population.
The first step implies examining the presence of neuropathic low back pain. Next, the differential diagnosis between predominant nociceptive and central sensitization pain is done using a clinical algorithm.
The classification criteria are substantiated by several original research findings including a Delphi survey, a study of a large group of LBP patients, and validation studies of the Central Sensitization Inventory. Nevertheless, these criteria require validation in clinical settings.
The pain classification system for LBP should be an addition to available classification systems and diagnostic procedures for LBP, as it is focussed on pain mechanisms solely.
Chronic pain, neuroscience, diagnosis, clinical reasoning, examination, assessment.
To evaluate the effectiveness of transcranial direct current stimulation alone and in combination with cognitive behavioural management in patients with non-specific chronic low back pain.
Double blind parallel group randomised controlled trial with six months' follow-up conducted May 2011-March 2013. Participants, physiotherapists, assessors, and analyses were blinded to group allocation.
Interdisciplinary chronic pain centre.
135 participants with non-specific chronic low back pain >12 weeks were recruited from 225 patients assessed for eligibility.
Participants were randomised to receive anodal (20 minutes to motor cortex at 2 mA) or sham transcranial direct current stimulation (identical electrode position, stimulator switched off after 30 seconds) for five consecutive days immediately before cognitive behavioural management (four week multidisciplinary programme of 80 hours).
Two primary outcome measures of pain intensity (0-100 visual analogue scale) and disability (Oswestry disability index) were evaluated at two primary endpoints after stimulation and after cognitive behavioural management.
Analyses of covariance with baseline values (pain or disability) as covariates showed that transcranial direct current stimulation was ineffective for the reduction of pain (difference between groups on visual analogue scale 1 mm (99% confidence interval -8.69 mm to 6.3 mm; P=0.68)) and disability (difference between groups 1 point (-1.73 to 1.98; P=0.86)) and did not influence the outcome of cognitive behavioural management (difference between group 3 mm (-10.32 mm to 6.73 mm); P=0.58; difference between groups on Oswestry disability index 0 point (-2.45 to 2.62); P=0.92). The stimulation was well tolerated with minimal transitory side effects.
This results of this trial on the effectiveness of transcranial direct current stimulation for the reduction of pain and disability do not support its clinical use for managing non-specific chronic low back pain.Trial registration Current controlled trials ISRCTN89874874.
© Luedtke et al 2015.
To investigate the efficacy and safety of paracetamol (acetaminophen) in the management of spinal pain and osteoarthritis of the hip or knee.
Systematic review and meta-analysis.
Medline, Embase, AMED, CINAHL, Web of Science, LILACS, International Pharmaceutical Abstracts, and Cochrane Central Register of Controlled Trials from inception to December 2014.
Randomised controlled trials comparing the efficacy and safety of paracetamol with placebo for spinal pain (neck or low back pain) and osteoarthritis of the hip or knee.
Two independent reviewers extracted data on pain, disability, and quality of life. Secondary outcomes were adverse effects, patient adherence, and use of rescue medication. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst possible pain or disability). We calculated weighted mean differences or risk ratios and 95% confidence intervals using a random effects model. The Cochrane Collaboration's tool was used for assessing risk of bias, and the GRADE approach was used to evaluate the quality of evidence and summarise conclusions.
12 reports (13 randomised trials) were included. There was "high quality" evidence that paracetamol is ineffective for reducing pain intensity (weighted mean difference -0.5, 95% confidence interval -2.9 to 1.9) and disability (0.4, -1.7 to 2.5) or improving quality of life (0.4, -0.9 to 1.7) in the short term in people with low back pain. For hip or knee osteoarthritis there was "high quality" evidence that paracetamol provides a significant, although not clinically important, effect on pain (-3.7, -5.5 to -1.9) and disability (-2.9, -4.9 to -0.9) in the short term. The number of patients reporting any adverse event (risk ratio 1.0, 95% confidence interval 0.9 to 1.1), any serious adverse event (1.2, 0.7 to 2.1), or withdrawn from the study because of adverse events (1.2, 0.9 to 1.5) was similar in the paracetamol and placebo groups. Patient adherence to treatment (1.0, 0.9 to 1.1) and use of rescue medication (0.7, 0.4 to 1.3) was also similar between groups. "High quality" evidence showed that patients taking paracetamol are nearly four times more likely to have abnormal results on liver function tests (3.8, 1.9 to 7.4), but the clinical importance of this effect is uncertain.
Paracetamol is ineffective in the treatment of low back pain and provides minimal short term benefit for people with osteoarthritis. These results support the reconsideration of recommendations to use paracetamol for patients with low back pain and osteoarthritis of the hip or knee in clinical practice guidelines.
PROSPERO registration number CRD42013006367.
© Machado et al 2015.
A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.
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.
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.
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.
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.
The mechanism of brain reorganization in pain chronification is unknown. In a longitudinal brain imaging study, subacute back pain (SBP) patients were followed over the course of 1 year. When pain persisted (SBPp, in contrast to recovering SBP and healthy controls), brain gray matter density decreased. Initially greater functional connectivity of nucleus accumbens with prefrontal cortex predicted pain persistence, implying that corticostriatal circuitry is causally involved in the transition from acute to chronic pain.
Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30
Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.
Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users.
Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions.
The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
To examine the efficacy of transcranial electrical stimulation a non-invasive method of reducing pain.
A randomized, double-blind, placebo-controlled trial.
A total of 119 patients with chronic pain.
Patients were treated with either transcranial electrical stimulation or an active placebo device. Short- and long-term follow-ups were evaluated for treatment efficacy with 4 ordinal scale variables: visual analogue scale (pain level), SLEEP (how often does pain disturb sleep), FREQ (frequency of pain) and MED (frequency of use of medications to relieve pain).
Pain level decreased significantly in the transcranial electrical stimulation-treated group compared with the active-placebo group 3 weeks after the end of treatment (p = 0.0017 between groups). Other parameters did not demonstrate significant differences. Three months after the end of treatment this effect was maintained and other treatment parameters showed similar improvements.
Transcranial electrical stimulation is an effective non-invasive method for pain relief. The active placebo device has a powerful effect on reported pain, which diminishes in the long-term. The involvement of possible neural mechanisms is discussed.
The goal of the study was to systematically review the global body of evidence surrounding the effectiveness of interventions for the prevention of acute pediatric agricultural injuries. A specific focus was the effectiveness of the North American Guidelines for Children's Agricultural Tasks.
Two reviewers independently screened studies and applied inclusion criteria on the basis of searches of 17 bibliographic databases (eg, Medline and Embase). We also screened reference lists of relevant studies and contacted experts in the area. Studies were included if they represented primary research, a comparison group was used, the study population included children or the intervention was directly applicable to children, and objective outcomes were reported. Two reviewers independently assessed the methodologic quality of included studies with the Downs and Black checklist. A qualitative analysis was performed because of extensive heterogeneity among studies.
We included 23 controlled studies, ie, 4 randomized, controlled trials, 5 controlled trials, and 14 quasiexperimental or observational studies. Only 8 of the relevant studies were published in peer-reviewed journals. School-based programs appeared to be effective at increasing short-term knowledge acquisition; outcomes were enhanced with active, hands-on participation, as opposed to passive activities. Safety day camps showed positive results for knowledge acquisition. Tractor training programs and community- and farm-based interventions showed mixed results. Studies examining the North American Guidelines for Children's Agricultural Tasks suggested that uptake improves if dissemination is accompanied by a farm visit from a safety specialist or if information about child development principles is provided in conjunction with the guidelines.
There is a lack of randomized, controlled trials and community-based trials in this area. Studies primarily examined intermediate outcomes, such as knowledge acquisition; few studies evaluated changes in injury rates. The interventions targeted at children and youths that were evaluated focused on educational interventions. There is both the need and potential for the development and evaluation of injury control interventions for children, particularly programs addressing lethal injuries to young/preschool-aged children.
Our understanding of the neural correlates of pain perception in humans has increased significantly since the advent of neuroimaging. Relating neural activity changes to the varied pain experiences has led to an increased awareness of how factors (e.g., cognition, emotion, context, injury) can separately influence pain perception. Tying this body of knowledge in humans to work in animal models of pain provides an opportunity to determine common features that reliably contribute to pain perception and its modulation. One key system that underpins the ability to change pain intensity is the brainstem's descending modulatory network with its pro- and antinociceptive components. We discuss not only the latest data describing the cerebral signature of pain and its modulation in humans, but also suggest that the brainstem plays a pivotal role in gating the degree of nociceptive transmission so that the resultant pain experienced is appropriate for the particular situation of the individual.
Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted by organisations worldwide Summary points Failure to consider the quality of evidence can lead to misguided recommendations; hormone replacement therapy for post-menopausal women provides an instructive example High quality evidence that an intervention’s desirable effects are clearly greater than its undesirable effects, or are clearly not, warrants a strong recommendationUncertainty about the trade-offs (because of low quality evidence or because the desirable and undesirable effects are closely balanced) warrants a weak recommendationGuidelines should inform clinicians what the quality of the underlying evidence is and whether recommendations are strong or weakThe Grading of Recommendations Assessment, Development and Evaluation (GRADE ) approach provides a system for rating quality of evidence and strength of recommendations that is explicit, comprehensive, transparent, and pragmatic and is increasingly being adopted by organisations worldwideGuideline developers around the world are inconsistent in how they rate quality of evidence and grade strength of recommendations. As a result, guideline users face challenges in understanding the messages that grading systems try to communicate. Since 2006 the BMJ has requested in its “Instructions to Authors” on bmj.com that authors should preferably use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence when submitting a clinical guidelines article. What was behind this decision?In this first in a series of five articles we will explain why many organisations use formal systems to grade evidence and recommendations and why this is important for clinicians; we will focus on the GRADE approach to recommendations. In the next two articles we will examine how the GRADE system categorises quality of evidence and strength of recommendations. The final two articles will …
Mechanism-based classification of pain has been advocated widely to aid tailoring of interventions for individuals experiencing persistent musculoskeletal pain. Three pain mechanism categories are defined by the International Association for the Study of Pain: nociceptive, neuropathic, and nociplastic pain. Discrimination between them remains challenging. This study aimed to: build on a framework developed to converge the diverse literature of pain mechanism categories to systematically review methods purported to discriminate between them; synthesise and thematically analyse these methods to identify convergence and divergence of opinion; and report validation, psychometric properties and strengths/weaknesses of these methods. The search strategy identified papers discussing methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system. Studies that assessed validity of methods to discriminate between categories were assessed for quality. Extraction and thematic analysis were undertaken on 184 papers. Data synthesis identified 200 methods in five themes: clinical examination, quantitative sensory testing, imaging, diagnostic and laboratory testing, and pain-type questionnaires. Few methods have been validated for discrimination between pain mechanism categories. There was general convergence but some disagreement regarding findings that discriminate between pain mechanism categories. A combination of features and methods, rather than a single method, was generally recommended to discriminate between pain mechanism categories. Two major limitations were identified: overlap of findings of methods between categories due to mixed presentations, and many methods considered discrimination between two pain mechanism categories but not others. The results of this review provide a foundation to refine methods to differentiate mechanisms for musculoskeletal pain.
Objectives:
Improvements in pain management might be achieved by matching treatment to underlying mechanisms for pain persistence. Many authors argue for a mechanism-based classification of pain, but the field is challenged by wide variation in proposed terminology, definitions and typical characteristics. This study aimed to: (i) systematically review mechanism-based classifications of pain experienced in the musculoskeletal system; (ii) synthesise and thematically analyse classifications, using the International Association for the Study of Pain categories of nociceptive, neuropathic and nociplastic as an initial foundation; and (iii) identify convergence and divergence between categories, terminology, and descriptions of each mechanism-based pain classification.
Methods:
Databases were searched for papers that discussed a mechanism-based classification of pain experienced in the musculoskeletal system. Terminology, definitions, underlying neurobiology/pathophysiology, aggravating/easing factors/response to treatment, and pain characteristics were extracted and synthesised based on thematic analysis.
Results:
From 224 papers, 174 terms referred to pain mechanisms categories. Data synthesis agreed with broad classification based on ongoing nociceptive input, neuropathic mechanisms, and nociplastic mechanisms (e.g. central sensitisation). “Mixed”, “other”, and the disputed categories of “sympathetic” and “psychogenic” pain, were also identified. Thematic analysis revealed convergence and divergence of opinion regarding definitions, underlying neurobiology and characteristics.
Discussion:
Some pain categories were defined consistently, and despite the extensive efforts to develop global consensus on pain definitions, disagreement still exists regarding how each could be defined, subdivided and their characteristic features that could aid differentiation. These data form a foundation for reaching consensus on classification.
Background:
Dry-electrode-based transcranial direct current stimulation is a new type of non-invasive brain stimulation system which relieves chronic low back pain and improves related muscle movement, in a way that overcomes the drawback of conventional systems.
Objective:
To investigate the effectiveness of dry-electrode-based transcranial direct current stimulation in relieving chronic low back pain and altering pain-related low back muscles movement, by using pain assessment tool and surface electromyographic topography.
Methods:
We conducted a prospective, double-blind, randomized, sham-controlled study. 60 patients with non-specific chronic low back pain were randomly and evenly allocated into tDCS and sham groups. Each group accepted a single 20-minute stimulation at 2 mA on the primary motor cortex. Numeric rating scale for pain intensity assessment and root-mean-square difference parameter from surface electromyographic topography were measured before and after stimulation. The current direction in brain using finite element method was simulated to verify the current distribution under dry stimulation electrode.
Results:
After stimulation, the pain intensity in the tDCS group significantly decreased, while it did not show evident change in the sham group. However, change of root-mean-square difference parameters between tDCS and sham groups showed no significant difference. Simulation results based on finite element method showed most of current focused on primary motor cortex while peak value of current density was 0.225 A/m2.
Conclusions:
Dry-electrode-based transcranial direct current stimulation can lower pain perception in patients with chronic low back pain. The analgesic mechanism can affect the top-down modulation pathway of pain.
The revised edition of the Handbook offers the only guide on how to conduct, report and maintain a Cochrane Review ? The second edition of The Cochrane Handbook for Systematic Reviews of Interventions contains essential guidance for preparing and maintaining Cochrane Reviews of the effects of health interventions. Designed to be an accessible resource, the Handbook will also be of interest to anyone undertaking systematic reviews of interventions outside Cochrane, and many of the principles and methods presented are appropriate for systematic reviews addressing research questions other than effects of interventions. This fully updated edition contains extensive new material on systematic review methods addressing a wide-range of topics including network meta-analysis, equity, complex interventions, narrative synthesis, and automation. Also new to this edition, integrated throughout the Handbook, is the set of standards Cochrane expects its reviews to meet. Written for review authors, editors, trainers and others with an interest in Cochrane Reviews, the second edition of The Cochrane Handbook for Systematic Reviews of Interventions continues to offer an invaluable resource for understanding the role of systematic reviews, critically appraising health research studies and conducting reviews.
High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has a good level of evidence of efficacy as a method for providing analgesic effects in patients with chronic pain. However, there is still no consensus regarding the parameters of stimulation to use and the detailed protocol to apply for therapeutic practice. In this article, we review the main technical points to address, and we propose a practical algorithm of how to use rTMS for chronic pain treatment in daily clinical practice.
Background and objective:
Chronic low back pain (CLBP) is highly prevalent, with a substantial psychosocial burden. Pain has both sensory and affective components. The latter component is a significant driver of disability and psychiatric comorbidity but is often inadequately treated. Previously we reported that noninvasive transcranial direct current stimulation (tDCS) may modulate pain-associated affective distress. Here we tested whether 10 daily tDCS sessions aimed to inhibit the left dorsal anterior cingulate cortex (dACC), a region strongly implicated in the affective component of pain, would produce selective reduction in pain-related symptoms.
Methods:
In this multisite, double-blinded, randomized placebo-controlled trial (RCT), 21 CLBP patients received 10 weekday sessions of 2-mA active tDCS or sham (20 minutes/session). A cathodal electrode was placed over FC1 (10-20 electroencephalography coordinates), and an identical anodal return electrode was placed over the contralateral mastoid. Participants rated pain intensity, acceptance, interference, disability, and anxiety, plus general anxiety and depression.
Results:
Regression analysis noted significantly less pain interference (P =0.002), pain disability (P =0.001), and depression symptoms (P =0.003) at six-week follow-up for active tDCS vs sham. Omnibus tests suggested that these improvements were not merely due to baseline (day 1) group differences.
Conclusions:
To our knowledge, this is the first double-blinded RCT of multiple tDCS sessions targeting the left dACC to modulate CLBP's affective symptoms. Results are encouraging, including several possible tDCS-associated improvements. Better-powered RCTs are needed to confirm these effects. Future studies should also consider different stimulation schedules, additional cortical targets, high-density multi-electrode tDCS arrays, and multimodal approaches.
Chronic pain is associated with maladaptive reorganization of the central nervous system. Recent studies have suggested that disorganization of large-scale electrical brain activity patterns such as neuronal network oscillations in the thalamo-cortical system plays a key role in the pathophysiology of chronic pain. Yet, little is known about if and how such network pathologies can be targeted with non-invasive brain stimulation as a non-pharmacological treatment option. We hypothesized that alpha oscillations, a prominent thalamo-cortical activity pattern in the human brain, are impaired in chronic pain and can be modulated with transcranial alternating current stimulation (tACS). We performed a randomized, crossover, double-blind, sham-controlled study in patients with chronic low back pain (CLBP) to investigate how alpha oscillations relate to pain symptoms for target identification and if tACS can engage this target and thereby induce pain relief. We used high-density electroencephalography to measure alpha oscillations and found that the oscillation strength in the somatosensory region at baseline before stimulation was negatively correlated with pain symptoms. Stimulation with alpha-tACS compared to sham (placebo) stimulation significantly enhanced alpha oscillations in the somatosensory region. The stimulation-induced increase of alpha oscillations in the somatosensory region was correlated with pain relief. Given these findings of successful target identification and engagement, we propose that modulating alpha oscillations with tACS may represent a target-specific, non-pharmacological treatment approach for CLBP. This trial has been registered in ClinicalTrials.gov (NCT03243084).
Transcranial direct current stimulation (tDCS) modulates spontaneous neuronal activity that can generate long-term neuroplastic changes. It has been used in numerous therapeutic trials showing significant clinical effects especially when combined with other behavioral therapies. One area of intensive tDCS research is chronic pain. Since the initial tDCS trials for chronic pain treatment using current parameters of stimulation, more than 60 clinical trials have been published testing its effects in different pain syndromes. However, as the field moves in the direction of clinical application, several aspects need to be taken into consideration regarding tDCS effectiveness and parameters of stimulation. In this article, we reviewed the evidence of tDCS effects for the treatment of chronic pain and critically analyzed the literature pertaining its safety and efficacy, and how to optimize tDCS clinical effects in a therapeutic setting. We discuss optimization of tDCS effects in 3 different domains: (i) parameters of stimulation, (ii) combination therapies, and (iii) subject selection. This article aims to provide insights for the development of future tDCS clinical trials.
Objective:
To test the efficacy of transcranial direct current stimulation (tDCS) in addition to group exercise on non-specific chronic low back pain.
Design:
Double-blinded randomized control trial.
Subjects:
Patients with non-specific chronic low back pain.
Methods:
A total of 35 subjects were recruited and allocated to real- or sham-tDCS followed by a group exercise protocol. Each patient underwent five sessions of brain stimulation followed by 10 sessions of group exercise. Subjects were evaluated before and after tDCS, after group exercise and one month after the combined treatment. Outcome measures were Visual Analog Scale for pain intensity, Roland Morris Disability Questionnaire, EuroQuol-5 Dimension and Patient Health Questionnaire-9.
Results:
Significant between-group difference in pain intensity (-27.7 ± 30.4 mm in real-tDCS group compared to -2.2 ± 30.1 mm in sham-tDCS group) and Patient Health Questionnaire-9 (-4.9 ± 4.2 in real-tDCS group compared to -1.1 ± 2.7 in sham-tDCS group) was found one month after the combined treatment ( P < 0.05).
Conclusion:
Our results showed that real-tDCS can induce significant larger effects on pain and psychological well-being, compared to sham-tDCS, when it is associated with a group exercise program. The effects were observed mostly in the follow-up.
Background:
Recent evidence suggests that chronic low back pain is associated with plastic changes in the brain that can be modified by neuromodulation strategies. This study investigated the efficacy of transcranial direct current stimulation (tDCS) combined simultaneously with peripheral electrical stimulation (PES) for pain relief, disability and global perception in patients with chronic low back pain (CLBP).
Methods:
Ninety-two patients with CLBP were randomized to receive 12 sessions on nonconsecutive days of anodal tDCS (primary motor cortex, M1), 100 Hz sensory PES (lumbar spine), tDCS + PES or sham tDCS + PES. Pain intensity (11-point numerical rating scale), disability and global perception were applied before treatment and four weeks, three months and six months post randomization.
Results:
A two points reduction was achieved only by the tDCS + PES (mean reduction [MR] = -2.6, CI95% = -4.4 to -0.9) and PES alone (MR = -2.2, CI95% = -3.9 to -0.4) compared with the sham group, but not of tDCS alone (MR = -1.7, CI95% = -3.4 to -0.0). In addition to maintaining the analgesic effect for up to three months, tDCS + PES had a higher proportion of respondents in different cutoff points. Global perception was improved at four weeks and maintained three months after treatment only with tDCS + PES. None of the treatments improved disability and the affective aspect of pain consistently with pain reduction.
Conclusion:
The results suggest that tDCS + PES and PES alone are effective in relieving CLBP in the short term. However, only tDCS + PES induced a long-lasting analgesic effect. tDCS alone showed no clinical meaningful pain relief.
Significance:
Transcranial direct current stimulation combined simultaneously with PES leads to a significant and clinical pain relief that can last up to three months in chronic low back pain patients. For this article, a commentary is available at the Wiley Online Library.
The objective of the present study was to assess the benefits of 1-week repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain (LBP). The visual analogue scale (VAS), Short Form McGill pain questionnaire (SF-MPQ), and Short Form 36 Health Survey were used to evaluate the effect of this treatment. Eighty-two patients diagnosed with LBP were divided randomly into three groups: rTMS-treated group, sham group, and physical therapy-treated group. We observed a significant reduction in VAS and SF-MPQ scores in the rTMS-treated group, but not in the sham group. Moreover, patients who received rTMS had a lower mean pain score than patients treated with physical therapy. Our study suggests that rTMS produces safe, significant, and long-term relief in patients with LBP without evident side effects. This study shows for the first time that long-term repeated sessions of rTMS decrease pain perception of LBP. Bioelectromagnetics.
Background:
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action.
Databases:
Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques.
Results:
Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections.
Conclusions:
rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action.
Stratified care for back pain involves targeting treatment to subgroups of patients based on their key characteristics such as prognostic factors, likely response to treatment and underlying mechanisms. It aims to tailor therapeutic decisions in ways that maximise treatment benefit, reduce harm and increase health-care efficiency by offering the right treatment to the right patient at the right time. From being called the 'Holy Grail' of back pain research over a decade ago, stratified care is becoming the zeitgeist in research and clinical practice. In this chapter, we introduce and evaluate the quality and underpinning evidence for three examples of stratified care for back pain to highlight their general principles, research design issues and clinical practice implications. We include consideration of their merits for implementation in practice. We conclude with a set of remaining, key research questions.
Study design:
Meta-analysis of randomized, controlled trials.
Objective:
To determine the short-term, intermediate, and long-term effectiveness of MCE, with regard to pain and disability, in patients with chronic and recurrent low-back pain.
Summary of background data:
Previous meta-analyses have shown no difference between the effects of MCE and general exercise in the treatment of low back pain. Several high quality studies on this topic have been published lately, warranting a new meta-analysis.
Methods:
We searched electronic databases up to October 2011 for randomized controlled trials clearly distinguishing MCE from other treatments. We extracted pain and disability outcomes and converted them to a 0 to 100 scale. We used the RevMan5 (Nordic Cochrane Centre, Copenhagen, Denmark) software to perform pooled analyses to determine the weighted mean differences (WMDs) between MCE and 5 different control interventions.
Results:
Sixteen studies were included. The pooled results favored MCE compared with general exercise with regard to disability during all time periods (improvement in WMDs ranged from -4.65 to -4.86), and with regard to pain in the short and intermediate term (WMDs were -7.80 and -6.06, respectively). Compared with spinal manual therapy, MCE was superior with regard to disability during all time periods (the WMDs ranged between -5.27 and -6.12), but not with regard to pain. Furthermore, MCE was superior to minimal intervention during all time periods with regard to both pain (the WMDs ranged between -10.18 and -13.32) and disability (the WMDs ranged between -5.62 and -9.00).
Conclusion:
In patients with chronic and recurrent low back pain, MCE seem to be superior to several other treatments. More studies are, however, needed to investigate what subgroups of patients experiencing LBP respond best to MCE.
Objectives:
To test the proof of principle that active anodal transcranial direct current stimulation (tDCS) applied to the motor cortex reduces pain significantly more than sham stimulation in a group of participants with chronic nonspecific low back pain.
Methods:
The study utilized a within-participants sham-controlled, interrupted time series design. A sample of 8 participants was recruited. After 3 days of baseline measures, patients entered a 15-day experimental period (Mondays to Fridays) for 3 consecutive weeks. During this period each patient received sham stimulation daily until a randomly allocated day when active stimulation was commenced. Active stimulation was then given daily for the remaining days of the experimental period. Both the participants and the assessors were blinded. The primary outcomes were average pain intensity and unpleasantness in the last 24 hours measured using a visual analogue scale. Secondary outcomes included self-reported disability, depression and anxiety, a battery of cognitive tests to monitor for unwanted effects of stimulation, and patients' perceptions of whether they had received active or sham stimulation. Data were analyzed using generalized estimating equations.
Results:
No significant effect was seen in the primary outcomes between active and sham stimulation (average pain intensity P = 0.821, unpleasantness P = 0.937) or across any other clinical variables. There was evidence that patients may have been able to distinguish between the active and sham conditions (P = 0.035).
Discussion:
These results do not provide evidence that tDCS is effective in the treatment of chronic back pain. The use of a small convenience sample limits the generalizability of these findings and precludes definitive conclusions on the efficacy of tDCS in chronic nonspecific low back pain.
This selective review discusses the psychobiological mediation of nociception and pain. Summarizing literature from physiology and neuroscience, first an overview of the neuroanatomic and neurochemical systems underpinning pain perception and modulation is provided. Second, findings from psychological science are used to elucidate cognitive, emotional, and behavioral factors central to the pain experience. This review has implications for clinical practice with patients suffering from chronic pain, and provides strong rationale for assessing and treating pain from a biopsychosocial perspective.
Neuromodulatory techniques with the ability to alter cortical excitability are gaining interest for their potential to enhance the brain's sensitivity to traditional therapies. Neuromodulatory techniques that prime the brain prior to manual or exercise therapy hold therapeutic promise for enhancing clinical outcomes in musculoskeletal and neurological conditions. The integration of these techniques into physiotherapy practice represents an exciting opportunity for the therapists of the future. Here, an overview is provided of three neuromodulatory techniques (peripheral electrical stimulation, transcranial direct current stimulation and repetitive transcranial magnetic stimulation) and the potential implications of these techniques for therapists discussed. Understanding these techniques and their therapeutic implications will ensure that therapists are well positioned to contribute to their clinical translation and adoption into clinical practice in an appropriate time frame. A therapeutic landscape defined by neuromodulatory techniques and improved clinical outcomes across a range of conditions is no longer far-fetched.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been shown to alter cortical excitability and activity via application of weak direct currents. Beyond intracortical effects, functional imaging as well as behavioral studies are suggesting additional tDCS-driven alterations of subcortical areas, however, direct evidence for such effects is scarce. We aimed to investigate the impact of tDCS on cortico-subcortical functional networks by seed functional connectivity analysis of different striatal and thalamic regions to prove tDCS-induced alterations of the cortico-striato-thalamic circuit. fMRI resting state data sets were acquired immediately before and after 10 min of bipolar tDCS during rest, with the anode/cathode placed over the left primary motor cortex (M1) and the cathode/anode over the contralateral frontopolar cortex. To control for possible placebo effects, an additional sham stimulation session was carried out. Functional coupling between the left thalamus and the ipsilateral primary motor cortex (M1) significantly increased following anodal stimulation over M1. Additionally, functional connectivity between the left caudate nucleus and parietal association cortices was significantly strengthened. In contrast, cathodal tDCS over M1 decreased functional coupling between left M1 and contralateral putamen. In summary, in this study, we show for the first time that tDCS modulates functional connectivity of cortico-striatal and thalamo-cortical circuits. Here we highlight that anodal tDCS over M1 is capable of modulating elements of the cortico-striato-thalamo-cortical functional motor circuit. Hum Brain Mapp 33:2499-2508, 2012. © 2011 Wiley Periodicals, Inc.
Low back pain is a major cause of morbidity in high-, middle- and low-income countries, yet to date it has been relatively under-prioritised and under-funded. One important reason may be the low ranking it has received relative to many other conditions included in the previous Global Burden of Disease studies, due in part to a lack of uniformity in how low back pain is defined and a paucity of suitable data. We present an overview of methods we have undertaken to ensure a more accurate estimate for low back pain in the Global Burden of Disease 2005 study. This will help clinicians to contextualise the new estimates and rankings when they become available at the end of 2010. It will also be helpful in planning further population-based epidemiological studies of low back pain to ensure their estimates can be included in the future Global Burden of Disease studies.
Unlabelled:
This pooled individual data (PID)-based meta-analysis collectively assessed the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on various neuropathic pain states based on their neuroanatomical hierarchy. Available randomized controlled trials (RCTs) were screened. PID was coded for age, gender, pain neuroanatomical origins, pain duration, and treatment parameters analyses. Coded pain neuroanatomical origins consist of peripheral nerve (PN); nerve root (NR); spinal cord (SC); trigeminal nerve or ganglion (TGN); and post-stroke supraspinal related pain (PSP). Raw data of 149 patients were extracted from 5 (1 parallel, 4 cross-over) selected (from 235 articles) RCTs. A significant (P < .001) overall analgesic effect (mean percent difference in pain visual analog scale (VAS) score reduction with 95% confidence interval) was detected with greater reduction in VAS with rTMS in comparison to sham. Including the parallel study (Khedr et al), the TGN subgroup was found to have the greatest analgesic effect (28.8%), followed by PSP (16.7%), SC (14.7%), NR (10.0%), and PN (1.5%). The results were similar when we excluded the parallel study with the greatest analgesic effect observed in TGN (33.0%), followed by SC (14.7%), PSP (10.5%), NR (10.0%), and PN (1.5%). In addition, multiple (vs single, P = .003) sessions and lower (>1 and < or =10 Hz) treatment frequency range (vs >10 Hz) appears to generate better analgesic outcome. In short, rTMS appears to be more effective in suppressing centrally than peripherally originated neuropathic pain states.
Perspective:
This is the first PID-based meta-analysis to assess the differential analgesic effect of rTMS on neuropathic pain based on the neuroanatomical origins of the pain pathophysiology and treatment parameters. The derived information serves as a useful resource in regards to treatment parameters and patient population selection for future rTMS-pain studies.
To test the feasibility of creating a valid and reliable checklist with the following features: appropriate for assessing both randomised and non-randomised studies; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting, internal validity (bias and confounding) and power, but also for external validity.
A pilot version was first developed, based on epidemiological principles, reviews, and existing checklists for randomised studies. Face and content validity were assessed by three experienced reviewers and reliability was determined using two raters assessing 10 randomised and 10 non-randomised studies. Using different raters, the checklist was revised and tested for internal consistency (Kuder-Richardson 20), test-retest and inter-rater reliability (Spearman correlation coefficient and sign rank test; kappa statistics), criterion validity, and respondent burden.
The performance of the checklist improved considerably after revision of a pilot version. The Quality Index had high internal consistency (KR-20: 0.89) as did the subscales apart from external validity (KR-20: 0.54). Test-retest (r 0.88) and inter-rater (r 0.75) reliability of the Quality Index were good. Reliability of the subscales varied from good (bias) to poor (external validity). The Quality Index correlated highly with an existing, established instrument for assessing randomised studies (r 0.90). There was little difference between its performance with non-randomised and with randomised studies. Raters took about 20 minutes to assess each paper (range 10 to 45 minutes).
This study has shown that it is feasible to develop a checklist that can be used to assess the methodological quality not only of randomised controlled trials but also non-randomised studies. It has also shown that it is possible to produce a checklist that provides a profile of the paper, alerting reviewers to its particular methodological strengths and weaknesses. Further work is required to improve the checklist and the training of raters in the assessment of external validity.
The authors show that in the human transcranial direct current stimulation is able to induce sustained cortical excitability elevations. As revealed by transcranial magnetic stimulation, motor cortical excitability increased approximately 150% above baseline for up to 90 minutes after the end of stimulation. The feasibility of inducing long-lasting excitability modulations in a noninvasive, painless, and reversible way makes this technique a potentially valuable tool in neuroplasticity modulation.
Cohort study of patients with low back pain (LBP) receiving physical therapy.
To examine the responsiveness characteristics of the numerical pain rating scale (NPRS) in patients with LBP using a variety of methods.
Although several studies have assessed the reliability and validity of the NPRS, few studies have characterized its responsiveness in patients with LBP.
Determination of change on the NPRS during 1 and 4 weeks was examined by calculating mean change, standardized effect size, Guyatt Responsiveness Index, area under a receiver operating characteristic curve, minimum clinically important difference, and minimum detectable change. Change in the NPRS from baseline to the 1 and 4-week follow-up was compared to the average of the patient and therapist's perceived improvement using the 15-point Global Rating of Change scale.
The majority of patients had clinically meaningful improvement after both 1 and 4 weeks of rehabilitation. The standard error of measure was equal to 1.02, corresponding to a minimum detectable change of 2 points. The area under the curve at the 1 and 4-week follow-up was 0.72 (0.62, 0.81) and 0.92 (0.86, 0.97), respectively. The minimum clinically important difference at the 1 and 4-week follow-up corresponded to a change of 2.2 and 1.5 points, respectively.
Clinicians can be confident that a 2-point change on the NPRS represents clinically meaningful change that exceeds the bounds of measurement error.
Research has shown that transcranial magnetic stimulation (TMS) results in a transient reduction in the experience of chronic pain. The present research aimed to investigate whether a single session of high frequency TMS is able to change the sensory thresholds of individuals suffering from chronic pain. Detection and pain thresholds for cold and heat sensations were measured before and after 20Hz repetitive TMS (rTMS) administered over the motor cortex. A significant decrease in temperature for cold detection and pain thresholds and a significant increase in temperature for heat pain thresholds were evident following a single session of rTMS. In contrast, no change in detection and pain thresholds was obtained following sham rTMS. The finding that rTMS can have a direct effect on sensory thresholds in individuals suffering from chronic pain has implications for the therapeutic use of rTMS in the relief of chronic pain.
We aimed to evaluate empirically how crossover trial results are analysed in meta-analyses of randomized evidence and whether their results agree with parallel arm studies on the same questions.
We used a systematic sample of Cochrane meta-analyses including crossover trials. We evaluated the methods of analysis for crossover results and compared the concordance of the estimated effect sizes in crossover vs parallel arm trials.
Of 334 screened reviews, 62 had crossover trials. Of those, 33 meta-analyses performed quantitative syntheses involving two-arm two-period crossover trials. There was large variability on how these trials were analysed; only one of the 33 meta-analyses stated that they used the data from both the first and second period with an appropriate paired approach. Nine meta-analyses used the first period data only and 14 gave no information at all on what they had done. Twenty-eight meta-analyses had both crossover (n = 137, sample size n = 7,162) and parallel arm (n = 132, sample size n = 11,398) trials. Effect sizes correlated well with the two types of designs (rho = 0.72). Differences on whether the summary effect had a P < 0.05 or not were common due to limited sample sizes. The summary relative odds ratio for parallel arm vs crossover designs for favourable outcomes was 0.87 (95% CI, 0.74-1.02).
Crossover designs may contribute evidence in a fifth of systematic reviews, but few meta-analyses make use of their full data. The results of crossover trials tend to agree with those of parallel arm trials, although there was a trend for more conservative treatment effect estimates in parallel arm trials.
Motor cortex stimulation (MCS) is relatively recent neurosurgical technique for pain control, the use of which is growing steadily since its description in the last decade. While clinical series show that at least 50% of patients with chronic, pharmacoresistant neuropathic pain may benefit from this technique, the mechanisms of action of MCS remain elusive. In this review, we synthesise a number of studies that, combining electrophysiology and functional imaging, have permitted to proceed from phenomenology to models that may account for part of such mechanisms. MCS appears to trigger rapid and phasic activation in the lateral thalamus, which leads to a cascade of events of longer time-course in medial thalamus, anterior cingulate/orbitofrontal cortices and periaqueductal grey matter. Activity in these latter structures is delayed relative to actual cortical neurostimulation and becomes maximal during the hours that follow MCS arrest. Current hypotheses suggest that MCS may act through at least two mechanisms: activation of perigenual cingulate and orbitofrontal areas may modulate the emotional appraisal of pain, rather than its intensity, while top down activation of brainstem PAG may lead to descending inhibition toward the spinal cord. Recent evidence also points to a possible secretion of endogenous opioids triggered by chronic MCS. This, along with the delayed and long-lasting activation of several brain structures, is consistent with the clinical effects of MCS, which may also last for hours or days after MCS discontinuation.