TMS for Neuropathic Pain

Overseen By Dennis Lambert

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Chronic pain medications

Disqualifiers: Dementia, Seizure disorder, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 2 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential new treatment for chronic neuropathic pain using repetitive transcranial magnetic stimulation (rTMS), which uses magnetic pulses to influence brain activity. The goal is to determine if high-frequency rTMS can effectively reduce pain that has not responded to other treatments. Participants will receive either high or low-frequency rTMS to their motor cortex to identify which method works best. Individuals with constant pain in their face or limbs for over six months, who have not found relief with current medications, might be suitable for this trial. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatment options for chronic pain sufferers.

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 prior data suggests that this rTMS treatment is safe for neuropathic pain?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for treating nerve pain. Studies have found that both high-frequency and low-frequency rTMS are well-tolerated. Specifically, a review of several studies found high-frequency rTMS to be safe and effective in reducing pain. The FDA has already approved this treatment for other conditions like depression and migraine, indicating its safety.

For low-frequency rTMS, evidence also supports its safety. Research shows it is well-tolerated and effective for other pain conditions. Both types of rTMS use magnetic pulses to alter brain activity and have fewer side effects than many pain medications. Overall, rTMS treatments are safe, with mild side effects like slight discomfort at the treatment site, which usually resolve quickly. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about high frequency repetitive transcranial magnetic stimulation (rTMS) for neuropathic pain because it offers a non-invasive approach by using magnetic fields to stimulate the motor cortex, which is quite different from traditional medications like opioids or anticonvulsants. Unlike these drugs, which often come with significant side effects or risk of dependency, high frequency rTMS targets specific areas of the brain, potentially providing relief without those drawbacks. Additionally, this method could be more effective for patients who haven't responded well to existing treatments, offering hope for better pain management.

What evidence suggests that this trial's treatments could be effective for neuropathic pain?

This trial will compare high-frequency repetitive transcranial magnetic stimulation (rTMS) with low-frequency rTMS for neuropathic pain. Research has shown that high-frequency rTMS, which participants in this trial may receive, can reduce long-term nerve pain. Specifically, studies have found that applying high-frequency rTMS to the primary motor cortex (M1) can significantly decrease pain, with some patients experiencing a noticeable drop in pain levels. Multiple sessions of this treatment often lead to even better pain relief. Meanwhile, low-frequency rTMS, another treatment option in this trial, has been helpful for conditions like fibromyalgia, but its effectiveness for nerve pain remains less certain. Overall, high-frequency rTMS appears promising for managing long-term nerve pain, based on current research. ^{5 6 7 8 9}

Who Is on the Research Team?

Julian C Motzkin, MD/PhD

Principal Investigator

University of California, San Francisco

Prasad Shirvalkar, MD/PHD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive daily rTMS sessions for 10 consecutive weekdays

2 weeks

10 visits (in-person)

Optional Extension

Participants may receive additional stimulation at the same or new target region

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

3 visits (in-person) at 1 week, 1 month, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• High Frequency rTMS
• Low Frequency rTMS

Trial Overview 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.

How Is the Trial Designed?

Group I: High Frequency rTMS Experimental Treatment 1 Intervention

High frequency 10 Hz stimulation of motor cortex (M1)

Group II: Low Frequency rTMS Active Control 1 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

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) is a promising non-invasive treatment for neuropathic pain (NP), which is often difficult to manage with traditional medications due to ineffectiveness and side effects.

Recent advancements in TMS technology, including neuronavigation systems that use MRI for precise targeting, may enhance its efficacy and support the need for larger clinical trials to gain regulatory approval for treating neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain-At the Tipping Point? Treister, R., Lang, M., Klein, MM., et al.[2021]

In a study of 34 patients with malignant neuropathic pain, 10 sessions of real repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex resulted in significant short-term pain relief compared to sham treatment, as measured by various pain and depression scales.

The pain relief effects from rTMS were observed to last for up to 15 days after treatment, indicating its potential as a therapeutic option for managing malignant neuropathic pain, although the benefits did not persist beyond one month.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in neuropathic pain secondary to malignancy: a randomized clinical trial. Khedr, EM., Kotb, HI., Mostafa, MG., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) applied to the M1/S1 cortex significantly lowers μ-opioid receptor availability, indicating the release of endogenous opioids in various brain regions associated with pain processing, which may contribute to its pain-relieving effects.

Despite the activation of the endogenous opioid system, rTMS did not change thermal pain thresholds or sensory discrimination of painful stimuli, suggesting that while rTMS enhances opioid-mediated inhibition, it does not alter the perception of pain intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids. Lamusuo, S., Hirvonen, J., Lindholm, P., et al.[2018]

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has been shown to provide short-term therapeutic effects for patients suffering from therapy-refractory neuropathic pain.

The results suggest that rTMS can predict the benefits of more invasive treatments like epidural motor cortex stimulation (MCS), indicating a potential pathway for effective pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain]. Mylius, V., Ayache, SS., Teepker, M., et al.[2021]

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is effective in reducing neuropathic pain, with significant pain relief observed after just one and five treatment sessions, based on a meta-analysis of 25 studies involving 589 patients.

The analgesic effects of HF-rTMS can last for at least one month after five sessions, indicating its potential for long-term pain management in neuropathic pain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Frequency Repetitive Transcranial Magnetic Stimulation Therapy For Chronic Neuropathic Pain: A Meta-analysis. Jin, Y., Xing, G., Li, G., et al.[2018]

In a study involving 70 patients with neuropathic pain, 10 daily sessions of repetitive transcranial magnetic stimulation (rTMS) showed significant short-term pain relief compared to sham treatment, as measured by visual analogue scale (VAS) and the short form of the McGill pain questionnaire (SF-MPQ).

The treatment was found to be safe, with no serious adverse events reported, indicating that daily high-frequency rTMS is a tolerable option for providing modest pain relief in neuropathic pain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial. Hosomi, K., Shimokawa, T., Ikoma, K., et al.[2022]

A study involving 66 patients with neuropathic pain showed that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) targeting the specific pain region using navigation techniques provided significant pain relief, particularly for upper and lower limb pain.

The pain relief from navigated rTMS lasted for one week, indicating that navigation may enhance the efficacy of rTMS compared to traditional non-navigated methods, although it was less effective for facial or diffuse pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain. Ayache, SS., Ahdab, R., Chalah, MA., et al.[2022]

Motor cortex stimulation can effectively control neuropathic pain in many patients, and repetitive transcranial magnetic stimulation (rTMS) can provide analgesic effects as well.

In a reported case, a woman with drug-resistant peripheral pain experienced 16 months of pain relief from monthly rTMS sessions before receiving a surgical cortical stimulator, highlighting rTMS as a valuable interim treatment before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. Lefaucheur, JP., Drouot, X., Ménard-Lefaucheur, I., et al.[2011]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduces neuropathic pain, with a notable overall analgesic effect compared to sham treatment, as shown in a meta-analysis of 149 patients from 5 randomized controlled trials.

The greatest pain relief was observed in patients with trigeminal nerve pain (28.8% reduction), followed by post-stroke pain (16.7%) and spinal cord pain (14.7%), indicating that rTMS is more effective for centrally originated pain compared to peripheral sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS for suppressing neuropathic pain: a meta-analysis. Leung, A., Donohue, M., Xu, R., et al.[2022]

In a study involving 17 patients with spinal cord injury and chronic neuropathic pain, repetitive transcranial magnetic stimulation (rTMS) did not show a significant advantage over sham treatment in reducing pain levels, indicating that its analgesic effect may not be superior to placebo.

Despite the lack of significant difference compared to sham treatment, rTMS did provide encouraging pain relief at 10 days and 6 weeks post-treatment, suggesting potential for further research with larger sample sizes to explore its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury. Yılmaz, B., Kesikburun, S., Yaşar, E., et al.[2021]

Citations

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High Frequency Repetitive Transcranial Magnetic ... All 3 HF-rTMS treatments (5, 10, and 20 Hz) produced pain reduction, while there were no differences between them, with the maximal pain reduction found after ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9433245/

The Effectiveness of High-Frequency Repetitive Transcranial ... There is moderate-to-high evidence to prove that high-frequency rTMS is effective in reducing pain in individuals with NOP, but it has no significant positive ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07187219

Efficacy of Repetitive Transcranial Magnetic Stimulation ... High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) has shown its efficacy to alleviate pain ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763421005315

Effects of repetitive transcranial magnetic stimulation on ... The results show that high-frequency rTMS can evidently relieve NP, and multiple sessions of stimulus can produce greater therapeutic effect.

5. nature.com nature.com/articles/s41598-024-62018-x

Repetitive transcranial magnetic stimulation focusing on ... Based on the results of our previous randomized controlled trial, the average reduction in VAS pain intensity was 38.8 for active rTMS. The ...

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Safety and recommendations for TMS use in healthy subjects ... Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

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Repetitive transcranial magnetic stimulation for ... Here we review the basic technique and mechanism of rTMS and discuss guidelines and future directions of rTMS in neuropathic pain treatment.

8. painphysicianjournal.com painphysicianjournal.com/current/pdf?article=MjQ0Nw%3D%3D&journal=92

High Frequency Repetitive Transcranial Magnetic ... Results: Twenty-five studies (including 32 trials and 589 patients) were selected for the meta- analysis according to the inclusion and exclusion criteria.

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Efficacy and safety of repetitive transcranial magnetic ... The study demonstrated that rTMS is an effective and safe way to reduce pain, improve QOL, enhance sensory status, and create a positive clinical impression in ...