Abstract:Objectives:The aim of the present study was to investigate the analgesic effects of repetitive transcranial magnetic stimulation over the primary motor cortex (M1-rTMS) using different stimulation parameters to explore the optimal stimulus condition for treating neuropathic pain.
Materials and Methods:We conducted a randomized, blinded, crossover exploratory study. Four single sessions of M1-rTMS at different parameters were administered in random order. The tested stimulation conditions were as follows: 5-Hz … Show more
“…However, the impact of TMS frequency and pulse number remains poorly understood and may present an opportunity to optimise analgesic efficacy and promote long-term effects. Prior work indicated that a single session consisting of 2,000, but not 500 pulses of 10Hz rTMS, was necessary to induce a significant alleviation of neuropathic pain relative to sham stimulation [7]. At least 1,000 pulses per session is recommended by the European Academy of Neurology, with the suggestion that increasing the pulse number may increase analgesic efficacy [2].…”
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
“…However, the impact of TMS frequency and pulse number remains poorly understood and may present an opportunity to optimise analgesic efficacy and promote long-term effects. Prior work indicated that a single session consisting of 2,000, but not 500 pulses of 10Hz rTMS, was necessary to induce a significant alleviation of neuropathic pain relative to sham stimulation [7]. At least 1,000 pulses per session is recommended by the European Academy of Neurology, with the suggestion that increasing the pulse number may increase analgesic efficacy [2].…”
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
“…We extracted randomized controlled trials (RCTs) of rTMS using the figure-of-8 coil for neuropathic pain, conducted at Osaka University Hospital as the main study institution, because this was the first attempt to review the analgesic effects at different pain sites. We included three of our previous clinical trials in this meta-analysis (Hosomi et al, 2013(Hosomi et al, , 2020Mori et al, 2021b). Hosomi et al (2013) conducted a randomized, double-blind, sham-controlled trial, from 2009 to 2011, at seven centers in Japan, to assess the efficacy and safety of 10 daily doses of rTMS in patients with neuropathic pain.…”
Section: Study Design Studies Selection and Data Sourcementioning
confidence: 99%
“…The mean decrease in VAS score was calculated using the procedure described by Hosomi et al (2013). Finally, in a trial by Mori et al (2021b), a randomized, single-blind, sham-controlled, crossover exploratory study was conducted from 2017 to 2018 at Osaka University Hospital to explore the optimal stimulus conditions for treating neuropathic pain. Four single sessions of M1-rTMS at different parameters (1, 5-Hz with 500 pulses per session; 2, 10-Hz with 500 pulses per session; 3, 10-Hz with 2000 pulses per session; and 4, sham stimulation) were conducted in random order.…”
Section: Study Design Studies Selection and Data Sourcementioning
confidence: 99%
“…Four single sessions of M1-rTMS at different parameters (1, 5-Hz with 500 pulses per session; 2, 10-Hz with 500 pulses per session; 3, 10-Hz with 2000 pulses per session; and 4, sham stimulation) were conducted in random order. From the data of Mori et al (2021b), we used VAS decrease, which was calculated by subtracting the VAS score immediately after the intervention from that immediately before the intervention for this analysis. Since Mori et al (2021b) conducted a crossover study examining four different stimulation conditions, the results of the rTMS condition (10 Hz over M1 hand, 2000 pulses/session) that produced significantly more effective pain relief compared with the sham stimulation were extracted and integrated into the present study.…”
Section: Study Design Studies Selection and Data Sourcementioning
confidence: 99%
“…From the data of Mori et al (2021b), we used VAS decrease, which was calculated by subtracting the VAS score immediately after the intervention from that immediately before the intervention for this analysis. Since Mori et al (2021b) conducted a crossover study examining four different stimulation conditions, the results of the rTMS condition (10 Hz over M1 hand, 2000 pulses/session) that produced significantly more effective pain relief compared with the sham stimulation were extracted and integrated into the present study. These studies were approved by the institutional review boards, and written informed consent was obtained from all participants.…”
Section: Study Design Studies Selection and Data Sourcementioning
High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex for neuropathic pain has been shown to be effective, according to systematic reviews and therapeutic guidelines. However, our large, rigorous, investigator-initiated, registration-directed clinical trial failed to show a positive primary outcome, and its subgroup analysis suggested that the analgesic effect varied according to the site of pain. The aim of this study was to investigate the differences in analgesic effects of rTMS for neuropathic pain between different pain sites by reviewing our previous clinical trials. We included three clinical trials in this mini meta-analysis: a multicenter randomized controlled trial at seven hospitals (N = 64), an investigator-initiated registration-directed clinical trial at three hospitals (N = 142), and an exploratory clinical trial examining different stimulation parameters (N = 22). The primary efficacy endpoint (change in pain scale) was extracted for each patient group with pain in the face, upper limb, or lower limb, and a meta-analysis of the efficacy of active rTMS against sham stimulation was performed. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated for pain change using a random-effects model. The analgesic effect of rTMS for upper limb pain was favorable (SMD = −0.45, 95% CI: −0.77 to −0.13). In contrast, rTMS did not produce significant pain relief on lower limb pain (SMD = 0.04, 95% CI: −0.33 to 0.41) or face (SMD = −0.24, 95% CI: −1.59 to 1.12). In conclusion, these findings suggest that rTMS provides analgesic effects in patients with neuropathic pain in the upper limb, but not in the lower limb or face, under the conditions of previous clinical trials. Owing to the main limitation of small number of studies included, many aspects should be clarified by further research and high-quality studies in these patients.
Background and ObjectiveRepetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex provides supplementary relief for some individuals with chronic pain who are refractory to pharmacological treatment. As rTMS slowly enters treatment guidelines for pain relief, its starts to be confronted with challenges long known to pharmacological approaches: efficacy at the group‐level does not grant pain relief for a particular patient. In this review, we present and discuss a series of ongoing attempts to overcome this therapeutic challenge in a personalized medicine framework.Databases and Data TreatmentRelevant scientific publications published in main databases such as PubMed and EMBASE from inception until March 2023 were systematically assessed, as well as a wide number of studies dedicated to the exploration of the mechanistic grounds of rTMS analgesic effects in humans, primates and rodents.ResultsThe main strategies reported to personalize cortical neuromodulation are: (i) the use of rTMS to predict individual response to implanted motor cortex stimulation; (ii) modifications of motor cortex stimulation patterns; (iii) stimulation of extra‐motor targets; (iv) assessment of individual cortical networks and rhythms to personalize treatment; (v) deep sensory phenotyping; (vi) personalization of location, precision and intensity of motor rTMS. All approaches except (i) have so far low or moderate levels of evidence.ConclusionsAlthough current evidence for most strategies under study remains at best moderate, the multiple mechanisms set up by cortical stimulation are an advantage over single‐target ‘clean’ drugs, as they can influence multiple pathophysiologic paths and offer multiple possibilities of individualization.SignificanceNon‐invasive neuromodulation is on the verge of personalised medicine. Strategies ranging from integration of detailed clinical phenotyping into treatment design to advanced patient neurophysiological characterisation are being actively explored and creating a framework for actual individualisation of care.
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