TMS for Chronic pain



Abstract

INTRODUCTION:

Complex Regional Pain Syndrome (CRPS), a rare and severe chronic pain condition, often responds poorly to existing treatments. Previous studies demonstrated Transcranial Magnetic Stimulation (TMS) provided short-term pain relief for upper extremity CRPS.

METHODS:

Building on previous methodologies, we employed a TMS protocol that may lead to significant pain relief for upper and lower extremity CRPS in a nonrandomized open label pilot trial involving 21 participants. We individualized TMS coil positioning over motor cortex of somatic pain location, and administered intermittent theta-burst stimulation followed by 10 Hz high-frequency stimulation using a deeper targeting coil. We assessed response (≥30% pain reduction) from a single session (n = 5) and five consecutive daily sessions (n = 12) and compared change in pain from baseline, after one treatment and one-week posttreatment between groups using a mixed ANVOA.

RESULTS:

Both groups demonstrated significant pain reduction after one session and one-week posttreatment; however, no group differences were present. From a single session, 60% of participants responded at Week 1. From five sessions, 58% and 50% of participants responded at Weeks 1 and 2, respectively. Two from each group achieved >50% pain reduction beyond six to eight weeks. No serious adverse events occurred. Though headache and nausea were the most common side-effects, we urge careful monitoring to prevent seizures with this protocol.

CONCLUSIONS:

We used a TMS protocol that, for the first time, led to significant pain relief in upper and lower extremity CRPS, and will soon examine our protocol in a larger, controlled trial.


In this study, assessments of pain improvement were undertaken by blinded physicians, who were naïve to a patient’s cohort designation. Blinded assessments were not done in prior studies with motor cortex stimulation, which may have introduced a form of operator bias into final subjective assessments about pain control. Thus, by the sound methodology of blinded review of a patient’s analgesic response, this study was immune to this form of bias.

The short-term and long-term assessments of pain control and quality of life were included in the longitudinal analysis of transcranial and intracranial stimulation. Though beneficial to survey patients several years after implantation to deduce longevity of analgesia, there would have been some merit to evaluating patients at shorter intervals, such as yearly or every two years to assess the average time to peak efficacy.

The use of both qualitative and quantitative measures of pain relief has more global and clinically-relevant merit than prior studies, which relied on pain score measures. Long-term MCS results on the HowRu questionnaire showed that modulation of anxiety, depression, and vocational/avocational disability measures lagged beyond the noted improvement in physical pain and autonomy. This may be due to recall bias and underestimation of the absolute pain improvement and functioning from a remote point in time.

In addition, the long-term assessment of pain relief carried out over 2-9 years provides a solid basis to determine if pain relief afforded by epidural motor cortex stimulation is fleeting or enduring. Quality of life assessments should be included in future longitudinal studies.

Only 20 patients were studied, and the power of the study is limited. The patient population was not homogeneous, with patients presenting with diverse etiologies of medically refractory neuropathic pain, from central post-stroke pain to trigeminal neuralgia to peripheral brachial plexopathy.

Only three patients experienced interval improvement in pain scores from the 6 months to the mean 6 years assessments. This again may reflect intrinsic differences of this population (concurrent pharmacologic use, central pain etiology more amenable to MCS, concurrent neuroses/psychoses). It would be interesting to explore the neurophysiologic basis of the procedure and explore whether certain pain pathways are more responsive to this modality. For now, this surgical option remains one of adjuvant utility to gold standards of pain management.

Of course, the study was conducted at only one medical center and external validity was reduced, but these results certainly may guide neurologists and neurosurgeons to conduct future higher-powered studies beyond this pilot study, which nevertheless, provides predictive outcomes of this innovative procedure for intractable neuropathic pain.


Abstract:

We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (53.38 ± 53.12% vs 22.93 ± 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30–60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. Perspective: High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.

Study Population
Fifty-four patients (mean age, 33.9 6 8.41 years; 4female patients) were included in the study. The participants were prospectively selected from the rehabilitation department of the Regional Military Hospital and local nongovernmental organizations in Bucaramanga, Colombia. Patients were included if they fulfilled the
following criteria: adults aged 18 years or older, who had amputation at any level of 1 lower limb by antipersonnel land mines with symptoms compatible with PLP. PLP was defined as a sensation of shooting, stabbing, boring, squeezing, throbbing, or burning or paresthesia or any other pain sensation in a limb that did not exist
anymore.
We excluded patients with a diagnosis of complex regional pain syndrome, any pathology that could alter the course of PLP (diagnosis of cancer, immunological
disorders, renal insufficiency requiring dialysis treatment, etc), pregnancy, neuropsychiatric disorders that can affect the patient ability to consent to the study
participation and contraindications to rTMS, such as cardiac pacemaker, medical pumps, or implanted metals in the scalp.47 This study was performed in accordance
with the Declaration of Helsinki (1964).8 Written informed consent was obtained from each participant before inclusion in the study, which was approved by the local institutional review board.

Randomization
A computer-generated randomization method with a permuted block size of 6 was used to allocate subjects to the sham or active rTMS interventions. The randomization code was only given to the treating investigator on the first day of treatment session by an independent investigator not involved with any other aspect of the trial.

Intervention: rTMS
Patients received rTMS on the primary motor cortex (M1) contralateral to the amputated leg using a figureof-eight coil connected to a Magstim Rapid2 magnetic stimulator, which provides a biphasic pulse (Magstim Company Ltd, Whitland, UK). The coil was positioned tangentially to the scalp, approximately at a 45 angle from the midline. The resting motor threshold (RMT) (of the first dorsal interosseous) was defined as the minimal intensity to induce motor evoked potentials of 50 mV peak-to-peak amplitude in at least 5 of 10 trials. Twenty trains of 6 seconds each (intertrain interval 54 seconds), using an intensity of 90% of RMT and 10 Hz frequency, were applied in each patient for 10 days during a 2-week period. For the sham treatment group, stimulation parameters were the same (location and duration), but a sham coil (Magstim Company Ltd) was used.

Results
Fifty-four patients (n = 27 in the active group and n = 27 in the sham group) were included in the study.


Abstract

OBJECTIVE:

Evidence suggests that fibromyalgia (FM) is a centrally mediated pain disorder. Antidepressants, including electroconvulsive therapy, provide some symptomatic relief in FM and other pain disorders. Repetitive transcranial magnetic stimulation (rTMS) is a new antidepressant treatment, which may also be useful in treating chronic pain.

DESIGN:

As part of a larger study, four women with depression, FM, and borderline personality disorder received 1-Hz rTMS applied to the right dorsolateral prefrontal cortex. Subjects rated pain using an 11-point Likert scale.

RESULTS:

Pretreatment pain averaged 8.2 (7-9.5) and reduced to 1.5 (0-3.5) after treatment (P < 0.009). All had improvement in pain, and two had complete resolution of pain. Only one of the four subjects had an antidepressant response.

CONCLUSIONS:

These preliminary findings suggest a possible role for rTMS in treating FM.


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