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      Noninvasive Transcranial Magnetic Stimulation (TMS) in Chronic Refractory Pain: A Systematic Review

      review-article
      1 , , 2 , 3
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      Cureus
      Cureus
      chronic pain, noninvasive management, randomized controlled trials, magnetic transcranial stimulation

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          Abstract

          Efficacy and tolerance of pharmacological medications in chronic pain are limited. Therefore, repetitive transcranial magnetic stimulation (rTMS) is regarded as a secure therapeutic option for pain relief, and it was proven to produce an analgesic effect. A wide variety of stimulation parameters can influence its long-lasting antalgic effect. Defining the best stimulation protocol can afford greater uniformity and consistency for considering rTMS as a promising effective tool. We aimed to systematically review and evaluate the current literature on transcranial magnetic stimulation for patients suffering from chronic pain, assess its efficacy, and estimate the best stimulation protocol. The Screened and tested electronic databases comprised PubMed, Ovid Medline, Cochrane database library, and Google scholar from the year 2000 till 2018. The keywords utilizing search terms “Transcranial magnetic stimulation”, “chronic pain”, “neuropathic pain” were used to study all possible randomized clinical trials about the impact of transcranial magnetic stimulation on long-lasting pain. All articles were judged for the possibility of prejudice using the Cochrane risk of bias tool for data extraction. Search engines produced seventy applicable results. Twelve randomized controlled clinical trials were included involving 350 patients with focal and generalized chronic pain. An existing proof showed a null response of low-frequency rTMS stimulation, rTMS delivered to the dorsolateral prefrontal cortex in chronic pain patients. However, a witnessed pain-killing response was documented when applying active high- frequency TMS on the motor cortex M1 area compared to sham. Pain relief was detected for a short time following the application of active high-frequency motor cortex stimulation in nine clinical trials, and the long-lasting analgesic effect was proved. No side effects were mentioned for the technique. Repetitive TMS can produce clinically meaningful relief from chronic pain, despite positive results, heterogeneity among all studies preclude firm conclusions regarding the optimal target stimulation site and parameters. Further studies are required to minimize bias, enhance performance, and define the best brain stimulation conditions and qualifications to maximize its potency. 

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          Most cited references30

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          The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.

          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.
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            Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia.

            The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation (rTMS), applied bilaterally over the dorsolateral prefrontal cortex (DLPFC), on cognitive function and cortical excitability of patients with Alzheimer's disease (AD). Forty-five AD patients were randomly classified into three groups. The first two groups received real rTMS over the DLPFC (20 and 1 Hz, respectively) while the third group received sham stimulation. All patients received one session daily for five consecutive days. In each session, rTMS was applied first over the right DLPFC, immediately followed by rTMS over the left DLPFC. Mini Mental State Examination (MMSE), Instrumental Daily Living Activity (IADL) scale and the Geriatric Depression Scale (GDS) were assessed before, after the last (fifth) session, and then followed up at 1 and 3 months. Neurophysiological evaluations included resting and active motor threshold (rMT and aMT), and the duration of transcallosal inhibition (TI) before and after the end of the treatment sessions. At base line assessment there were no significant differences between groups in any of the rating scales. The high frequency rTMS group improved significantly more than the low frequency and sham groups in all rating scales (MMSE, IADL, and GDS) and at all time points after treatment. Measures of cortical excitability immediately after the last treatment session showed that treatment with 20 Hz rTMS reduced TI duration. These results confirm that five daily sessions of high frequency rTMS over the left and then the right DLPFC improves cognitive function in patients with mild to moderate degree of AD. This improvement was maintained for 3 months. High frequency rTMS may be a useful addition to therapy for the treatment of AD.
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              Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain.

              A single session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex had been reported to produce short term relief of some types of chronic pain. The present study investigated whether five consecutive days of rTMS would lead to longer lasting pain relief in unilateral chronic intractable neuropathic pain. Forty eight patients with therapy resistant chronic unilateral pain syndromes (24 each with trigeminal neuralgia (TGN) and post-stroke pain syndrome (PSP)) participated. Fourteen from each group received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10x10 s trains, intensity 80% of motor threshold) every day for five consecutive days. The remaining patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before, after the first, fourth, and fifth sessions, and two weeks after the last session. No significant differences were found in basal pain ratings between patients receiving real- and sham-rTMS. However, a two factor ANOVA revealed a significant "+/- TMS" x "time" interaction indicating that real and sham rTMS had different effects on the VAS and LANSS scales. Post hoc testing showed that in both groups of patients, real-rTMS led to a greater improvement in scales than sham-rTMS, evident even two weeks after the end of the treatment. No patient experienced adverse effects. These results confirm that five daily sessions of rTMS over motor cortex can produce longlasting pain relief in patients with TGN or PSP.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                29 October 2019
                October 2019
                : 11
                : 10
                : e6019
                Affiliations
                [1 ] Researcher, California Institute of Behavioral Neuroscience and Psychology, Fairfield, USA
                [2 ] Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
                [3 ] Internal Medicine, Stanley Medical College, Chennai, IND
                Author notes
                Article
                10.7759/cureus.6019
                6886641
                31824787
                2633f13e-4940-4c78-9e80-b6c83d935694
                Copyright © 2019, Hamid et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 September 2019
                : 28 October 2019
                Categories
                Psychiatry
                Neurology
                Healthcare Technology

                chronic pain,noninvasive management,randomized controlled trials,magnetic transcranial stimulation

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