Trial Summary
What is the purpose of this trial?Chronic neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system. It is highly prevalent, debilitating, and challenging to treat. Current available treatments have low efficacy, high side effect burden, and are prone to misuse and dependence. Emerging evidence suggests that the transition from acute to chronic neuropathic pain is associated with reorganization of central brain circuits involved in pain processing. Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative treatment that uses focused magnetic pulses to non-invasively modulate brain activity, a strategy that can potentially circumvent the adverse effects of available treatments for pain. RTMS is FDA-approved for the treatment of major depressive disorder, obsessive-compulsive disorder, and migraine, and has been shown to reduce pain scores when applied to the contralateral motor cortex (M1). However, available studies of rTMS for chronic neuropathic pain typically show variable and often short-lived benefits, and many aspects of optimal treatment remain unknown, including ideal rTMS stimulation parameters, duration of treatment, and relationship to the underlying pain etiology. Here the investigators propose to evaluate the efficacy of high frequency rTMS to M1, the region with most evidence of benefit in chronic neuropathic pain, and to use functional magnetic resonance imaging (fMRI) to identify alternative rTMS targets for participants that do not respond to stimulation at M1. The central aim is to evaluate the pain relieving efficacy of multi-session high-frequency M1 TMS for pain. In secondary exploratory analyses, the investigator propose to investigate patient characteristic that are predictive of responsive to M1 rTMS and identify viable alternative stimulation targets in non-responders to M1 rTMS.
Do I have to stop taking my current medications for the trial?
No, you don't have to stop taking your current medications. You need to be stable on your chronic pain medications for 4 weeks before the study and continue them throughout the study. Some medications will be reviewed by a TMS specialist to ensure they are safe to use with TMS.
What data supports the idea that TMS for Neuropathic Pain is an effective treatment?
The available research shows that repetitive transcranial magnetic stimulation (rTMS) can effectively relieve neuropathic pain. Studies indicate that high-frequency rTMS applied to specific brain areas can reduce pain. For example, a meta-analysis found that rTMS is more effective for pain that originates in the central nervous system compared to pain from peripheral nerves. Additionally, research suggests that rTMS may work by releasing natural pain-relieving chemicals in the brain. Overall, these findings support the idea that TMS is a promising treatment for neuropathic pain.
12345What safety data exists for TMS in treating neuropathic pain?
The safety data for TMS in treating neuropathic pain indicates that it is generally well-tolerated. In a randomized, multicenter, double-blind, crossover, sham-controlled trial, no serious adverse events were observed with daily high-frequency rTMS of the primary motor cortex. This suggests that TMS is a safe treatment option for neuropathic pain, although the analgesic effects are modest and transient.
13678Is the treatment High Frequency rTMS promising for neuropathic pain?
Yes, High Frequency rTMS is a promising treatment for neuropathic pain. It can relieve pain by stimulating the brain non-invasively, and studies show it can provide long-lasting pain relief. It is already approved for treating depression and has shown effectiveness in small studies for neuropathic pain.
127910Eligibility Criteria
This trial is for adults aged 18-80 with chronic neuropathic pain lasting over 6 months due to nerve damage or disease. Participants must have a certain level of continuous pain, be able to tolerate the procedures, and give informed consent. They should be stable on their current pain medications and not pregnant, nursing, or have specific psychiatric conditions or contraindications for TMS.Inclusion Criteria
I have been on the same pain medication for 4 weeks and can continue it during the study.
I have been on the same pain medication for 4 weeks and can continue during the study.
I have been diagnosed with chronic nerve pain.
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Exclusion Criteria
I am not pregnant or nursing.
I am unable to commit to the full duration of the study.
I have not had major psychiatric disorders, thoughts of suicide, brain surgery, or electroconvulsive therapy.
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Participant Groups
The study tests high frequency rTMS versus low frequency rTMS as treatments for chronic neuropathic pain. It aims to determine if stimulating the brain's motor cortex can reduce pain by modulating brain activity without the side effects common in other treatments.
2Treatment groups
Experimental Treatment
Active Control
Group I: High Frequency rTMSExperimental Treatment1 Intervention
High frequency 10 Hz stimulation of motor cortex (M1)
Group II: Low Frequency rTMSActive Control1 Intervention
Low frequency 1 Hz stimulation of motor cortex (M1)
High Frequency rTMS is already approved in United States for the following indications:
🇺🇸 Approved in United States as rTMS for:
- Major Depressive Disorder
- Obsessive-Compulsive Disorder
- Migraine
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCSF Medical CenterSan Francisco, CA
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Who Is Running the Clinical Trial?
University of California, San FranciscoLead Sponsor
References
High Frequency Repetitive Transcranial Magnetic Stimulation Therapy For Chronic Neuropathic Pain: A Meta-analysis. [2018]Increasing evidence supports an analgesic effect of repetitive transcranial magnetic stimulation (rTMS) for neuropathic pain (NP). However, the optimal parameters of rTMS (stimulation frequency and treatment sessions) for achieving long-term analgesic effects remain unknown. This study analyzed the current findings in the literature.
Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain. [2022]Repetitive transcranial magnetic stimulation (rTMS) can relieve neuropathic pain when applied at high frequency (HF: 5-20 Hz) over the primary motor cortex (M1), contralateral to pain side. In most studies, rTMS is delivered over the hand motor hot spot (hMHS), whatever pain location. Navigation systems have been developed to guide rTMS targeting, but their value to improve rTMS efficacy remains to be demonstrated.
rTMS for suppressing neuropathic pain: a meta-analysis. [2022]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 1 and 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.
Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids. [2018]Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain.
The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury. [2021]To investigate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on intractable neuropathic pain in patients with spinal cord injury (SCI).
Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial. [2022]There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single-session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double-blind, sham-controlled, crossover study at 7 centers. Seventy NP patients were randomly assigned to 2 groups. A series of 10 daily 5-Hz rTMS (500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patient with a follow-up of 17days. The primary outcome was short-term pain relief assessed using a visual analogue scale (VAS). The secondary outcomes were short-term change in the short form of the McGill pain questionnaire (SF-MPQ), cumulative changes in the following scores (VAS, SF-MPQ, the Patient Global Impression of Change scale [PGIC], and the Beck Depression Inventory [BDI]), and the incidence of adverse events. Analysis was by intention to treat. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry. Sixty-four NP patients were included in the intention-to-treat analysis. The real rTMS, compared with the sham, showed significant short-term improvements in VAS and SF-MPQ scores without a carry-over effect. PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS. There were no significant cumulative improvements in VAS, SF-MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high-frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients.
Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain-At the Tipping Point? [2021]The term "neuropathic pain" (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain's surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include "frameless stereotactic" neuronavigation systems, in which patients' head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials.
Repetitive transcranial magnetic stimulation in neuropathic pain secondary to malignancy: a randomized clinical trial. [2022]Significant analgesic effects of repetitive transcranial magnetic stimulation (rTMS) have been found in several studies of patients with chronic pain of various origins, but never for malignancy. The objective of this study was to assess the efficacy of 10 sessions of rTMS over the primary motor cortex (M1) in patients suffering from malignant neuropathic pain.
Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. [2011]Neuropathic pain can be controlled by motor cortex stimulation using surgically-implanted electrodes in a majority of selected patients. Analgesic effects were also found to result from repetitive transcranial magnetic stimulation (rTMS) of the cortex. We report the case of a woman, in whom drug-resistant peripheral pain was controlled for 16 months by monthly sessions of motor cortex rTMS until a durable pain relief was obtained after surgical implantation of a cortical stimulator. This case illustrates the value of rTMS in helping patients to wait for surgery.
[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain]. [2021]Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.