Traitement de la douleur
Neuroreport. 2001 Sep 17;12(13):2963-5.
Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex.
Lefaucheur JP, Drouot X, Keravel Y, Nguyen JP.
Services de Physiologie, Explorations Fonctionnelles, Hopital Henri Mondor, 51 avenue de Lattre de Tassigny, 94010 Creteil, France.
Chronic electrical stimulation of the precentral (motor) cortex using surgically implanted electrodes is performed to treat medication-resistant neurogenic pain. The goal of this placebo-controlled study was to obtain such antalgic effects by means of a non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS). Eighteen patients with intractable neurogenic pain of various origins were included and underwent a 20 min session of either 10 Hz, 0.5 Hz or* sham rTMS over the motor cortex in a random order. A significant decrease in the mean pain level of the series was obtained only after 10 Hz rTMS. This study shows that a transient pain relief can be induced by 10 Hz rTMS of the motor cortex in some patients suffering from chronic neurogenic pain.
PMID: 11588611 [PubMed - index pour MEDLINE]
Neurophysiol Clin. 2001 Aug;31(4):247-52.
Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex.
Lefaucheur JP, Drouot X, Nguyen JP.
Service de physiologie-explorations fonctionnelles, hôpital Henri-Mondor, Inserm U421, faculté de médecine, 94010 Créteil, France. firstname.lastname@example.org
The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body, by means of surgically-implanted epidural electrodes is a validated therapeutical strategy to control medication-resistant neurogenic pain. Repetitive transcranial magnetic stimulation (rTMS) permits to stimulate non-invasively and precisely the motor cortex. We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a 'real' or a 'sham' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy. We studied the effects of rTMS on pain level assessed on a 0-10 visual analogue scale from day 1 to day 12 following the rTMS session. A significant pain decrease was observed up to 8 days after the 'real' rTMS session. This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex.
PMID: 11601430 [PubMed - index pour MEDLINE]
J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):612-6.
Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain.
Lefaucheur JP, Drouot X, Menard-Lefaucheur I, Zerah F, Bendib B, Cesaro P, Keravel Y, Nguyen JP.
Service de Physiologie-Explorations Fonctionnelles, Hôpital Henri Mondor, 51 Avenue de Lattre de Tassigny, 94010 Créteil, France. email@example.com
Drug resistant neurogenic pain can be relieved by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. This study was designed to assess the influence of pain origin, pain site, and sensory loss on rTMS efficacy.
PATIENTS AND METHODS:
Sixty right handed patients were included, suffering from intractable pain secondary to one of the following types of lesion: thalamic stroke, brainstem stroke, spinal cord lesion, brachial plexus lesion, or trigeminal nerve lesion. The pain predominated unilaterally in the face, the upper limb, or the lower limb. The thermal sensory thresholds were measured within the painful zone and were found to be highly or moderately elevated. Finally, the pain level was scored on a visual analogue scale before and after a 20 minute session of "real" or "sham" 10 Hz rTMS over the side of the motor cortex corresponding to the hand on the painful side, even if the pain was not experienced in the hand itself.
and discussion: The percentage pain reduction was significantly greater following real than sham rTMS (-22.9% v -7.8%, p = 0.0002), confirming that motor cortex rTMS was able to induce antalgic effects. These effects were significantly influenced by the origin and the site of pain. For pain origin, results were worse in patients with brainstem stroke, whatever the site of pain. This was consistent with a descending modulation within the brainstem, triggered by the motor corticothalamic output. For pain site, better results were obtained for facial pain, although stimulation was targeted on the hand cortical area. Thus, in contrast to implanted stimulation, the target for rTMS procedure in pain control may not be the area corresponding to the painful zone but an adjacent one. Across representation plasticity of cortical areas resulting from deafferentation could explain this discrepancy. Finally, the degree of sensory loss did not interfere with pain origin or pain site regarding rTMS effects.
Motor cortex rTMS was found to result in a significant but transient relief of chronic pain, influenced by pain origin and pain site. These parameters should be taken into account in any further study of rTMS application in chronic pain control.
PMID: 15026508 [PubMed - index pour MEDLINE]
J Neurol Neurosurg Psychiatry. 2005 Jun;76(6):833-8.
Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain.
Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC.
Department of Neurology, Assiut University Hospital, Assiut, Egypt. Emankhedr99@yahoo.com
BACKGROUND AND OBJECTIVE:
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.
PATIENTS AND METHODS:
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.
PMID: 15897507 [PubMed - index pour MEDLINE]
Pain. 2006 May;122(1-2):22-7. Epub 2006 Feb 21.
Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex.
Hirayama A, Saitoh Y, Kishima H, Shimokawa T, Oshino S, Hirata M, Kato A, Yoshimine T.
Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation-guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10-s 5-Hz TMS pulses, with 50-s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF-MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief (p<0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 (p<0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.
PMID: 16495011 [PubMed - index pour MEDLINE]
Neurophysiol Clin. 2006 May-Jun;36(3):117-24. Epub 2006 Aug 23.
The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain.
Service de physiologie, explorations fonctionnelles, hôpital Henri-Mondor, Assistance-publique-Hôpitaux de Paris, 51, avenue du Marechal-Lattre-de-Tassigny, 94010 Créteil, France. firstname.lastname@example.org
Chronic motor cortex stimulation using implanted epidural stimulation was proposed to treat chronic, drug-resistant neuropathic pain. Various studies showed that repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex could also relieve neuropathic pain, at least partially and transiently. Controlled rTMS studies with other cortical targets, such as the dorsolateral prefrontal cortex, are in waiting. The mechanisms of action of rTMS on chronic pain are mostly unknown. The changes induced by rTMS in neural activities may occur at the stimulated cortical site as well as in remote structures along functional anatomical connections. Compared to chronic implanted procedure, the main limitation of rTMS application is the short duration of clinical effects. Repeated daily rTMS sessions have proved some efficacy to induce long-lasting pain relief that could have therapeutic potential. However, rTMS-induced analgesia varies with the site and parameters of stimulation, in particular the stimulus rate. The efficacious rTMS parameters could differ from those used in chronic epidural stimulation. Differences in the pattern of the current fields respectively induced in the brain by these two techniques might explain this finding. Actually, stimulation parameters remain to be optimised and clinical efficacy to be confirmed by multicentre randomised trials, before considering rTMS as therapeutic tool for patients with chronic pain in neurological practice.
PMID: 17046606 [PubMed - index pour MEDLINE]
Neurology. 2006 Nov 14;67(9):1568-74.
Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain.
Lefaucheur JP, Drouot X, Ménard-Lefaucheur I, Keravel Y, Nguyen JP.
Department of Physiology, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, INSERM U 421, IM3-Faculté de Médecine de Créteil, Créteil, France. email@example.com
To assess cortical excitability changes in patients with chronic neuropathic pain at baseline and after repetitive transcranial magnetic stimulation (rTMS) of the motor cortex.
In 22 patients with unilateral hand pain of various neurologic origins and 22 age-matched healthy controls, we studied the following parameters of cortical excitability: motor threshold at rest, motor evoked potential amplitude ratio at two intensities, cortical silent period (CSP), and intracortical inhibition (ICI) and intracortical facilitation. We compared these parameters between healthy subjects and patients at baseline. We also studied excitability changes in the motor cortex corresponding to the painful hand of patients after active or sham rTMS of this cortical region at 1 or 10 Hz.
At baseline, CSP was shortened for the both hemispheres of patients vs healthy subjects, in correlation with pain score, while ICI was reduced only for the motor cortex corresponding to the painful hand. Regarding rTMS effects, the single significant change was ICI increase in the motor cortex corresponding to the painful hand, after active 10-Hz rTMS, in correlation with pain relief.
Chronic neuropathic pain was associated with motor cortex disinhibition, suggesting impaired GABAergic neurotransmission related to some aspects of pain or to underlying sensory or motor disturbances. The analgesic effects produced by motor cortex stimulation could result, at least partly, from the restoration of defective intracortical inhibitory processes.
PMID: 17101886 [PubMed - index pour MEDLINE]
Eur J Neurol. 2007 Sep;14(9):952-70.
EFNS guidelines on neurostimulation therapy for neuropathic pain.
Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur JP, Simpson BA, Taylor RS.
EFNS Panel on Neuropathic Pain, Vienna, Austria. firstname.lastname@example.org
Pharmacological relief of neuropathic pain is often insufficient. Electrical neurostimulation is efficacious in chronic neuropathic pain and other neurological diseases. European Federation of Neurological Societies (EFNS) launched a Task Force to evaluate the evidence for these techniques and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I (level B recommendation). High-frequency transcutaneous electrical nerve stimulation (TENS) may be better than placebo (level C) although worse than electro-acupuncture (level B). One kind of repetitive transcranial magnetic stimulation (rTMS) has transient efficacy in central and peripheral neuropathic pains (level B). Motor cortex stimulation (MCS) is efficacious in central post-stroke and facial pain (level C). Deep brain stimulation (DBS) should only be performed in experienced centres. Evidence for implanted peripheral stimulations is inadequate. TENS and r-TMS are non-invasive and suitable as preliminary or add-on therapies. Further controlled trials are warranted for SCS in conditions other than failed back surgery syndrome and CRPS and for MCS and DBS in general. These chronically implanted techniques provide satisfactory pain relief in many patients, including those resistant to medication or other means.
PMID: 17718686 [PubMed - index pour MEDLINE]
Brain. 2007 Oct;130(Pt 10):2661-70. Epub 2007 Sep 14.
Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.
Passard A, Attal N, Benadhira R, Brasseur L, Saba G, Sichere P, Perrot S, Januel D, Bouhassira D.
INSERM U-792, Boulogne-Billancourt F-92100 France.
Non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems. Neuroimaging studies have shown bilateral activation of a large number of structures, including some of those involved in pain processing, suggesting that such stimulation may induce generalized analgesic effects. The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia. Thirty patients with fibromyalgia syndrome (age: 52.6 +/- 7.9) were randomly assigned, in a double-blind fashion, to two groups, one receiving active rTMS (n = 15) and the other sham stimulation (n = 15), applied to the left primary motor cortex in 10 daily sessions. The primary outcome measure was self-reported average pain intensity over the last 24 h, measured at baseline, daily during the stimulation period and then 15, 30 and 60 days after the first stimulation. Other outcome measures included: sensory and affective pain scores for the McGill pain Questionnaire, quality of life (assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire), mood and anxiety (assessed with the Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale). We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation. Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients (13 in each treatment group) on day 60. Active rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception. Only few minor and transient side effects were reported during the stimulation period. Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia.
PMID: 17872930 [PubMed - index pour MEDLINE]
Brain Stimul. 2008 Apr;1(2):122-7.
Significant analgesic effects of one session of postoperative left prefrontal cortex repetitive transcranial magnetic stimulation: a replication study.
Borckardt JJ, Reeves ST, Weinstein M, Smith AR, Shelley N, Kozel FA, Nahas Z, Byrne KT, Morgan K, George MS.
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA. email@example.com
In a recent preliminary trial in 20 patients after gastric bypass surgery, 20 minutes of repetitive transcranial magnetic stimulation (TMS) over the left prefrontal cortex was associated with a 40% reduction in postoperative patient-controlled morphine use. As is the case with all novel scientific findings, and especially those that might have an impact on clinical practice, replicability is paramount. This study sought to test this finding for replication and to more accurately estimate the effect size of this brief intervention on postoperative morphine use and postoperative pain and mood ratings.
Twenty participants who underwent gastric bypass surgery completed this replication and extension study. Beck Depression Inventory and Center for Epidemiological Studies Depression scale scores were collected before surgery and at the time of discharge from the hospital. Immediately after surgery, participants were randomly assigned to receive 20 minutes of real or sham repetitive TMS (rTMS) (10 Hz, 10 seconds-ON, 20 seconds-OFF for a total of 4000 pulses). Patient-controlled morphine pump usage was tracked throughout each participant's postoperative hospital stay. In addition, pain and mood ratings were collected via visual analogue scales twice per day.
Findings from the original postoperative TMS trial were replicated, as cumulative morphine usage curves were significantly steeper among patients receiving sham TMS, and participants receiving real TMS had used 35% less morphine at the time of discharge than participants receiving sham TMS. At the time of discharge, subjects who had received real TMS had used 42.50 mg of morphine, whereas subjects receiving sham TMS had used an average of 64.88 mg. When the data from the original preliminary trial were combined with the data from this replication trial, a significant difference in cumulative morphine usage was observed between subjects receiving real and sham TMS. Overall, participants who received real TMS used 36% less morphine and had significantly lower ratings of postoperative pain-on-average, and pain-at-its-worst than participants receiving sham. In addition, participants who received real TMS rated their mood-at-its-worst as significantly better than participants receiving sham. The effect of a single 20-minute session of TMS on postoperative pain and morphine use appears to be large (Cohen's d = 0.70) and clinically meaningful. Lastly, cross-lag correlational analyses indicate that improvements in mood follow improvements in pain by approximately 12 hours, supporting the notion that postoperative analgesic TMS effects are not driven by antidepressant effects.
Although more research is needed to verify these observed effects independently, findings from the original postoperative TMS trial were replicated. TMS may have the potential to significantly improve current standards of postoperative care among gastric bypass patients, and further studies may be warranted on other surgical populations. Future investigations should use methodology that permits more definitive conclusions about causal effects of TMS on postoperative pain (for example, double-blinding, sham stimulation that is matched with real TMS with respect to scalp discomfort).
PMID: 19759838 [PubMed - index pour MEDLINE]
Expert Rev Neurother. 2008 May;8(5):799-808.
Use of repetitive transcranial magnetic stimulation in pain relief.
Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, Avenue de Lattre de Tassigny, 94010 Créteil, France. firstname.lastname@example.org
Repetitive transcranial magnetic stimulation (rTMS) of the cerebral cortex is a noninvasive strategy that could have the potential to relieve severe chronic pain, at least partially and transiently. The most studied target of stimulation is the precentral (motor) cortex, but other targets, such as the dorsolateral prefrontal cortex or the parietal cortex, could be of interest. Analgesic effects have been produced by rTMS in patients with neuropathic pain, fibromyalgia or visceral pain. Therapeutic applications of rTMS in pain syndromes are limited by the short duration of the induced effects, but prolonged pain relief can be obtained by performing rTMS sessions every day for several weeks. In patients who respond to rTMS but relapse, surgical implantation of epidural cortical electrodes and a pulse generator can be proposed to make clinical effects more permanent. The rate of improvement produced by rTMS may be predictive for the outcome of the implanted procedure. The place of rTMS as a therapeutic tool in the management of chronic pain remains to be determined.
PMID: 18457536 [PubMed - index pour MEDLINE]
Neurology. 2008 Sep 9;71(11):833-40.
Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes.
André-Obadia N, Mertens P, Gueguen A, Peyron R, Garcia-Larrea L.
INSERM U879, University Claude Bernard Lyon 1, France. email@example.com
To assess, against placebo, the pain-relieving effects of high-rate repetitive transcranial magnetic stimulation (rTMS) on neuropathic pain.
Double-blind, randomized, cross-over study of high-rate rTMS against placebo in 28 patients. The effect of a change in coil orientation (posteroanterior vs lateromedial) on different subtypes of neuropathic pain was further tested in a subset of 16 patients. Pain relief was evaluated daily during 1 week.
High-frequency, posteroanterior rTMS decreased pain scores significantly more than placebo. Posteroanterior rTMS also outmatched placebo in a score combining subjective (pain relief, quality of life) and objective (rescue drug intake) criteria of treatment benefit. Changing the orientation of the coil from posteroanterior to lateromedial did not yield any significant pain relief. The analgesic effects of posteroanterior rTMS lasted for approximately 1 week. The pain-relieving effects were observed exclusively on global scores reflecting the most distressing type of pain in each patient. Conversely, rTMS did not modify specifically any of the pain subscores that were separately tested (ongoing, paroxysmal, stimulus-evoked, or disesthesic pain).
Posteroanterior repetitive transcranial magnetic stimulation (rTMS) was more effective than both placebo and lateromedial rTMS. When obtained, pain relief was not specific of any particular submodality, but rather reduced the global pain sensation whatever its type. This is in accord with recent models of motor cortex neurostimulation, postulating that its analgesic effects may derive in part from modulation of the affective appraisal of pain, rather than a decrease of its sensory components.
PMID: 18779511 [PubMed - index pour MEDLINE]
J Pain. 2010 Nov;11(11):1203-10. Epub 2010 Apr 28.
Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I.
Picarelli H, Teixeira MJ, de Andrade DC, Myczkowski ML, Luvisotto TB, Yeng LT, Fonoff ET, Pridmore S, Marcolin MA.
Clinic of Pain, Department of Neurology, University of São Paulo, Brazil.
Single-session repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) is effective in the treatment of chronic pain patients, but the analgesic effect of repeated sessions is still unknown. We evaluated the effects of rTMS in patients with refractory pain due to complex regional pain syndrome (CRPS) type I. Twenty-three patients presenting CRPS type I of 1 upper limb were treated with the best medical treatment (analgesics and adjuvant medications, physical therapy) plus 10 daily sessions of either real (r-) or sham (s-) 10 Hz rTMS to the motor cortex (M1). Patients were assessed daily and after 1 week and 3 months after the last session using the Visual Analogical Scale (VAS), the McGill Pain Questionnaire (MPQ), the Health Survey-36 (SF-36), and the Hamilton Depression (HDRS). During treatment there was a significant reduction in the VAS scores favoring the r-rTMS group, mean reduction of 4.65 cm (50.9%) against 2.18 cm (24.7%) in the s-rTMS group. The highest reduction occurred at the tenth session and correlated to improvement in the affective and emotional subscores of the MPQ and SF-36. Real rTMS to the M1 produced analgesic effects and positive changes in affective aspects of pain in CRPS patients during the period of stimulation. PERSPECTIVE: This study shows an efficacy of repetitive sessions of high-frequency rTMS as an add-on therapy to refractory CRPS type I patients. It had a positive effect in different aspects of pain (sensory-discriminative and emotional-affective). It opens the perspective for the clinical use of this technique.
Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.
PMID: 20430702 [PubMed - index pour MEDLINE]
Cochrane Database Syst Rev. 2010 Sep 8;(9):CD008208.
Non-invasive brain stimulation techniques for chronic pain.
O'Connell NE, Wand BM, Marston L, Spencer S, Desouza LH.
Centre for Research in Rehabilitation, School of Health Sciences and Social Care, Brunel University, Kingston Lane, Uxbridge, Middlesex, UK, UB8 3PH.
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) and transcranial direct current stimulation (tDCS).
To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain.
We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, the Cochrane PaPaS Group Trials Register and clinical trials registers.
Randomised and quasi-randomised studies of rTMS, CES or tDCS if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome.
DATA COLLECTION AND ANALYSIS:
Two authors independently extracted and verified data. Where possible we entered data into meta-analyses. We excluded studies judged as being at high risk of bias from the analysis.
We included 33 trials in the review (involving 937 people)(19 rTMS, eight CES and six tDCS). Only one study was judged as being at low risk of bias.Studies of rTMS (involving 368 participants ) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective. A short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies was suggested (standardised mean difference (SMD) -0.40, 95% confidence interval (CI) -0.26 to -0.54, P < 0.00001). This equates to a 15% (95% CI 10% to 20%) reduction in pain which does not clearly exceed the pre-established criteria for a minimally clinically important difference (> 15%).For CES (four studies, 133 participants) no statistically significant difference was found between active stimulation and sham. Analysis of tDCS studies (five studies, 83 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation. Pre-specified subgroup analysis of tDCS applied to the motor cortex suggested superiority of active stimulation over sham (SMD -0.59, 95% CI -1.10 to -0.08).Non-invasive brain stimulation appears to be associated with minor and transient side effects.
Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. The effects do not clearly exceed the predetermined threshold of minimal clinical significance. Low-frequency rTMS is not effective in the treatment of chronic pain. There is insufficient evidence from which to draw firm conclusions regarding the efficacy of CES or tDCS. The available evidence suggests that tDCS applied to the motor cortex may have short-term effects on chronic pain and that CES may be ineffective. There is a need for further, rigorously designed studies of all types of stimulation.
PMID: 20824873 [PubMed - index pour MEDLINE]
Pain. 2011 Feb;152(2):320-6. Epub 2010 Dec 10.
Neuropharmacological basis of rTMS-induced analgesia: the role of endogenous opioids.
de Andrade DC, Mhalla A, Adam F, Texeira MJ, Bouhassira D.
Centre d'Evaluation et de Traitement de la Douleur, Ambroise Paré, Boulogne-Billancourt, France.
We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). We compared the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, in a randomized, double-blind crossover design, in healthy volunteers. Three groups of 12 volunteers were selected at random and given active stimulation (frequency 10Hz, at 80% motor threshold intensity, 1500 pulses per session) of the right M1, active stimulation of the right DLPFC, or sham stimulation, during two experimental sessions 2 weeks apart. Cold pain thresholds and the intensity of pain induced by a series of fixed-temperature cold stimuli (5, 10, and 15°C) were used to evaluate the analgesic effects of rTMS. Measurements were made at the left thenar eminence, before and 1 hour after the intravenous injection of naloxone (bolus of 0.1mg/kg followed by a continuous infusion of 0.1mg/kg/h until the end of rTMS) or placebo (saline). Naloxone injection significantly decreased the analgesic effects of M1 stimulation, but did not change the effects of rTMS of the DLPFC or sham rTMS. This study demonstrates, for the first time, the involvement of endogenous opioid systems in rTMS-induced analgesia. The differential effects of naloxone on M1 and DLPFC stimulation suggest that the analgesic effects induced by the stimulation of these 2 cortical sites are mediated by different mechanisms. Endogenous opioids are shown to be involved in the analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21146300 [PubMed - index pour MEDLINE]
Pain. 2011 Jun;152(6):1233-7. Epub 2011 Feb 20.
On the importance of placebo timing in rTMS studies for pain relief.
André-Obadia N, Magnin M, Garcia-Larrea L.
INSERM U879, Central Integration of Pain Unit, Lyon, France. firstname.lastname@example.org
The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex for neuropathic pain relief is founded on double-blind studies versus placebo. In these studies, however, the analgesic effect of active interventions remained modest compared with the placebo effect. This observation led us to re-evaluate the intrinsic placebo action on pain relief according to the relative timing of active and sham rTMS interventions. In a randomized controlled study including 45 patients, we compared the analgesic effect of sham rTMS that either preceded or followed an active rTMS, which could be itself either successful or unsuccessful. Placebo analgesia differed significantly when the sham rTMS session followed a successful or an unsuccessful active rTMS. Placebo sessions induced significant analgesia when they followed a successful rTMS (mean pain decrease of 11%), whereas they tended to worsen pain when following an unsuccessful rTMS (pain increase of 6%). Only when the sham intervention was applied before any active rTMS were placebo scores unchanged from the baseline. These results probably reflect an unconscious conditioned learning. The timing of placebo relative to active interventions should be taken into account in rTMS studies for pain relief, and possibly in other conditions too. The fact that placebo effects could be enhanced by a previous rTMS with an analgesic effect as low as 10% suggests that a 30% pain decrease threshold in therapeutic trials may be too severe because smaller analgesic effects may have a clinical significance too. Sham rTMS induces significant analgesia only when preceded by a successful active stimulation. Such a placebo modulation is probably related to an unconscious conditioned learning.
Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Learned placebo analgesia in sequential trials: What are the Pros and Cons?Colloca L. Pain. 2011 Jun; 152(6):1215-6. Epub 2011 Mar 5.
PMID: 21342747 [PubMed - index pour MEDLINE]
Pain. 2011 Jul;152(7):1478-85. Epub 2011 Mar 11.
Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia.
Mhalla A, Baudic S, Ciampi de Andrade D, Gautron M, Perrot S, Teixeira MJ, Attal N, Bouhassira D.
INSERM U-987, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne-Billancourt F-92100, France.
We assessed for the first time the long-term maintenance of repetitive transcranial magnetic stimulation (rTMS)-induced analgesia in patients with chronic widespread pain due to fibromyalgia. Forty consecutive patients were randomly assigned, in a double-blind fashion, to 2 groups: one receiving active rTMS (n=20) and the other, sham stimulation (n=20), applied to the left primary motor cortex. The stimulation protocol consisted of 14 sessions: an "induction phase" of 5 daily sessions followed by a "maintenance phase" of 3 sessions a week apart, 3 sessions a fortnight apart, and 3 sessions a month apart. The primary outcome was average pain intensity over the last 24 hours, measured before each stimulation from day 1 to week 21 and at week 25 (1 month after the last stimulation). Other outcomes measured included quality of life, mood and anxiety, and several parameters of motor cortical excitability. Thirty patients completed the study (14 in the sham stimulation group and 16 in the active stimulation group). Active rTMS significantly reduced pain intensity from day 5 to week 25. These analgesic effects were associated with a long-term improvement in items related to quality of life (including fatigue, morning tiredness, general activity, walking, and sleep) and were directly correlated with changes in intracortical inhibition. In conclusion, these results suggest that TMS may be a valuable and safe new therapeutic option in patients with fibromyalgia.
Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Is rTMS a therapeutic option in chronic pain syndrome? Insights from the treatment of fibromyalgia.Lefaucheur JP. Pain. 2011 Jul; 152(7):1447-8. Epub 2011 Mar 29.
PMID: 21397400 [PubMed - index pour MEDLINE]
Pain. 2011 Jul;152(7):1447-8. Epub 2011 Mar 29.
Is rTMS a therapeutic option in chronic pain syndrome? Insights from the treatment of fibromyalgia.
Faculté de Médecine, Université Paris Est Créteil, Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique, Hôpitaux de Paris, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Créteil, France. email@example.com
Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia.Mhalla A, Baudic S, Ciampi de Andrade D, Gautron M, Perrot S, Teixeira MJ, Attal N, Bouhassira D. Pain. 2011 Jul; 152(7):1478-85. Epub 2011 Mar 11.
PMID: 21450403 [PubMed - index pour MEDLINE]
Pain. 2011 Nov;152(11):2477-84. Epub 2011 Jul 20.
Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: a randomized, controlled pilot study.
Short EB, Borckardt JJ, Anderson BS, Frohman H, Beam W, Reeves ST, George MS.
Brain Stimulation Laboratory, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President St., PO Box 250861, Charleston, SC 29425, USA. firstname.lastname@example.org
Transcranial magnetic stimulation (TMS) of the prefrontal cortex can cause changes in acute pain perception. Several weeks of daily left prefrontal TMS has been shown to treat depression. We recruited 20 patients with fibromyalgia, defined by American College of Rheumatology criteria, and randomized them to receive 4000 pulses at 10 Hz TMS (n=10), or sham TMS (n=10) treatment for 10 sessions over 2 weeks along with their standard medications, which were fixed and stable for at least 4 weeks before starting sessions. Subjects recorded daily pain, mood, and activity. Blinded raters assessed pain, mood, functional status, and tender points weekly with the Brief Pain Inventory, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire. No statistically significant differences between groups were observed. Patients who received active TMS had a mean 29% (statistically significant) reduction in pain symptoms in comparison to their baseline pain. Sham TMS participants had a 4% nonsignificant change in daily pain from their baseline pain. At 2 weeks after treatment, there was a significant improvement in depression symptoms in the active group compared to baseline. Pain reduction preceded antidepressant effects. TMS was well tolerated, with few side effects. Further studies that address study limitations are needed to determine whether daily prefrontal TMS may be an effective, durable, and clinically useful treatment for fibromyalgia symptoms.
Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Repetitive transcranial magnetic stimulation for chronic pain: time to evolve from exploration to confirmation?O'Connell NE, Wand BM. Pain. 2011 Nov; 152(11):2451-2. Epub 2011 Jun 23.
PMID: 21764215 [PubMed - index pour MEDLINE]
J Pain. 2011 Oct;12(10):1102-11. Epub 2011 Jul 31.
Predictive value of rTMS in the identification of responders to epidural motor cortex stimulation therapy for pain.
Lefaucheur JP, Ménard-Lefaucheur I, Goujon C, Keravel Y, Nguyen JP.
EA 4391, Faculté de Médecine de Créteil, Université Paris-Est-Créteil, Créteil, France. email@example.com
This study was designed to assess the value of repetitive transcranial magnetic stimulation (rTMS) to predict the efficacy of epidural motor cortex stimulation (EMCS) to treat neuropathic pain. We have included 59 patients treated by EMCS for more than 1 year and in whom active and sham 10Hz-rTMS sessions were performed as preoperative tests, targeted over the cortical representation of the painful area. Analgesic effects were rated on a visual analogue scale. The real rTMS efficacy was determined by subtracting the effect of the sham stimulation on pain scores from that of the active stimulation (active-sham calculation). Pain scores were significantly reduced by active rTMS and EMCS, but not by sham rTMS. Twenty-six of the 33 patients (79%) who responded to active rTMS and all the 21 patients (100%) who responded for active-sham calculation also responded to EMCS. The response observed in active-sham calculation had a positive predictive value of 1.0, but a negative predictive value of .6 regarding EMCS outcome. The analgesic effect of rTMS or EMCS was not influenced by the side, origin, or duration of pain or by the presence of motor or sensory deficit in the painful area. Poorer results were observed in case of lower limb pain for rTMS and in older patients for EMCS. This study confirms that neuropathic pain can be significantly relieved by motor cortex rTMS or EMCS. A positive outcome of EMCS can be predicted by a real response to rTMS, but not on clinical grounds. PERSPECTIVE: Single sessions of sham-controlled preoperative rTMS tests can be used to confirm the indication of EMCS therapy but have no value to exclude patients from this therapy. New rTMS protocols remain to be assessed to improve the usefulness of preoperative rTMS in EMCS practice.
Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
PMID: 21807565 [PubMed - index pour MEDLINE]
Pain. 2012 Jun;153(6):1219-25. Epub 2012 Mar 22.
Endogenous opioids mediate left dorsolateral prefrontal cortex rTMS-induced analgesia.
Taylor JJ, Borckardt JJ, George MS.
Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA.
The concurrent rise of undertreated pain and opiate abuse poses a unique challenge to physicians and researchers alike. A focal, noninvasive form of brain stimulation called repetitive transcranial magnetic stimulation (rTMS) has been shown to produce acute and chronic analgesic effects when applied to dorsolateral prefrontal cortex (DLPFC), but the anatomical and pharmacological mechanisms by which prefrontal rTMS induces analgesia remain unclear. Data suggest that DLPFC mediates top-down analgesia via gain modulation of the supraspinal opioidergic circuit. This potential pathway might explain how prefrontal rTMS reduces pain. The purpose of this sham-controlled, double-blind, crossover study was to determine whether left DLPFC rTMS-induced analgesia was sensitive to delta-opioid blockade. Twenty-four healthy volunteers were randomized to receive real or sham TMS after either intravenous saline or naloxone pretreatment. Acute hot and cold pain via quantitative sensory testing and hot allodynia via block testing on capsaicin-treated skin were assessed at baseline and at 0, 20, and 40minutes after TMS treatment. When compared to sham, real rTMS reduced hot pain and hot allodynia. Naloxone pretreatment significantly reduced the analgesic effects of real rTMS. These results demonstrate that left DLPFC rTMS-induced analgesia requires opioid activity and suggest that rTMS drives endogenous opioidergic pain relief in the human brain. Further studies with chronic dosing regimens of drugs that block or augment the actions of opiates are needed to determine whether TMS can augment opiates in chronic or postoperative pain management.
Copyright © 2012 International Association for the Study of Pain. All rights reserved.
PMID: 22444187 [PubMed - index pour MEDLINE]
Eur J Pain. 2012 Apr 16. doi: 10.1002/j.1532-2149.2012.00150.x. [Epub ahead of print]
Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: Influence of theta burst stimulation priming.
Lefaucheur JP, Ayache SS, Sorel M, Farhat WH, Zouari HG, Ciampi de Andrade D, Ahdab R, Ménard-Lefaucheur I, Brugières P, Goujon C.
Faculté de Médecine, Université Paris Est Créteil, France; Service de Physiologie - Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France.
'Conventional' protocols of high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to M1 can produce analgesia. Theta burst stimulation (TBS), a novel rTMS paradigm, is thought to produce greater changes in M1 excitability than 'conventional' protocols. After a preliminary experiment showing no analgesic effect of continuous or intermittent TBS trains (cTBS or iTBS) delivered to M1 as single procedures, we used TBS to prime a subsequent session of 'conventional' 10 MHz-rTMS.
In 14 patients with chronic refractory neuropathic pain, navigated rTMS was targeted over M1 hand region, contralateral to painful side. Analgesic effects were daily assessed on a visual analogue scale for the week after each 10 MHz-rTMS session, preceded or not by TBS priming. In an additional experiment, the effects on cortical excitability parameters provided by single- and paired-pulse TMS paradigms were studied.
Pain level was reduced after any type of rTMS procedure compared to baseline, but iTBS priming produced greater analgesia than the other protocols. Regarding motor cortex excitability changes, the analgesic effects were associated with an increase in intracortical inhibition, whatever the type of stimulation, primed or non-primed.
The present results show that the analgesic effects of 'conventional' 10 MHz-rTMS delivered to M1 can be enhanced by TBS priming, at least using iTBS. Interestingly, the application of cTBS and iTBS did not produce opposite modulations, unlike previously reported in other systems. It remains to be determined whether the interest of TBS priming is to generate a simple additive effect or a more specific process of cortical plasticity.
© 2012 European Federation of International Association for the Study of Pain Chapters.
PMID: 22508405 [PubMed - index pour MEDLINE]