TMS for Pain Modulation

Overseen By Carolina Valencia, PT, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Priyanka Rana, PT, MPT, PhD

Must not be taking: Pain medications, Blood thinners

Disqualifiers: Chronic pain, Blood disorders, Migraines, others

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

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the brain's pathways can control pain using Transcranial Magnetic Stimulation (TMS). It specifically examines the brain's natural ability to block pain signals and whether TMS can enhance this process, known as Conditioned Pain Modulation (CPM). The study will also investigate how factors such as stress and cultural background might influence this pain-blocking ability. Individuals who are pain-free and not taking regular pain medications may be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on pain management techniques.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you regularly use prescription pain medication or blood thinning medication.

What prior data suggests that Transcranial Magnetic Stimulation (TMS) is safe for pain modulation?

Previous studies have shown that Transcranial Magnetic Stimulation (TMS) is generally safe and well-tolerated. Research indicates that most people experience only mild side effects, such as a tingling or itching sensation where the electrodes are placed, along with possible tiredness, headache, nausea, or trouble sleeping. One study demonstrated that TMS remained safe even with a high number of pulses over several days. Only about 1 in 5 people needed to stop or reduce the treatment due to side effects. Overall, TMS appears to be a safe option for studying and potentially treating pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how transcranial magnetic stimulation (TMS) can modulate pain using a technique called Conditioned Pain Modulation (CPM). Unlike typical pain treatments that focus on medications like opioids or NSAIDs, this method uses magnetic fields to stimulate nerve cells in the brain. The trial investigates different exposure levels to TMS, which might reveal how varying frequencies or durations can optimize pain relief. This non-invasive approach could offer new insights into managing pain without the side effects associated with traditional medications.

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

This trial will compare different exposure levels to Conditioned Pain Modulation (CPM) to understand its effects on pain management. Research has shown that CPM can improve understanding of how the body handles pain, especially in individuals with long-term pain. Studies have found that CPM is less effective in those with chronic pain, highlighting its importance for exploring new treatments. The idea is that CPM might enhance the brain's natural ability to reduce or control pain. Researchers have tested this method in healthy individuals to determine its potential for improving chronic pain management. By enhancing these natural pain control pathways, CPM could help manage chronic pain more effectively. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for healthy adults interested in participating in a study on pain perception and modulation. Participants should be willing to undergo Transcranial Magnetic Stimulation (TMS) and engage in Conditioned Pain Modulation (CPM) tasks.

Inclusion Criteria

I do not experience any pain.

Exclusion Criteria

Systemic medical condition known to affect sensation

I regularly take prescribed medication to manage my pain.

I am currently taking medication to thin my blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including psychological questionnaires and psychophysical approaches to measure individual sensitivity, endogenous pain modulation, and transcranial magnetic stimulation.

1 week

1 visit (in-person)

Intervention

Participants receive repeated exposure to Conditioned Pain Modulation (CPM) and Transcranial Magnetic Stimulation (TMS) to assess and potentially modulate pain inhibitory mechanisms.

2 weeks

5 visits (in-person) for High Exposure group, 2 visits (in-person) for Low Exposure group

Follow-up

Participants are monitored for changes in cortical excitability and pain sensitivity after the intervention.

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Conditioned Pain Modulation (CPM)

Trial Overview

The study tests how the brain's pain control pathways work during CPM, using TMS as a tool. It also looks at whether factors like stress or optimism affect this process.

How Is the Trial Designed?

Group I: High Exposure (HE) Experimental Treatment 1 Intervention

Participants will receive five sessions total: four sessions of the Intervention, CPM and TMS as an outcome in every session and questionnaires and QST as an outcome in the first and fifth sessions.

Group II: Low Exposure (LE) Active Control 1 Intervention

Participants will receive only two sessions in total: one session of the intervention, questionnaires, quantitative sensory testing, CPM and TMS as an outcome at both sessions.

Group III: No Exposure (NE) Active Control 1 Intervention

Participants will receive only two sessions in total: questionnaires, quantitative sensory testing, and TMS as an outcome at both sessions.

Who Is Running the Clinical Trial?

Priyanka Rana, PT, MPT, PhD

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

In a study involving 101 healthy adults, various conditioned pain modulation (CPM) methods, including hot water immersion and cold pressor tests, were found to effectively reduce pain perception, with hot water immersion and cold pressor tests showing the strongest effects.

Factors such as gender, age, chronic stress, and attentional focus significantly influenced the effectiveness of these CPM methods, indicating that personal characteristics should be considered when evaluating pain modulation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of five conditioned pain modulation paradigms and influencing personal factors in healthy adults. Mertens, MG., Hermans, L., Crombez, G., et al.[2021]

In a case study of a 77-year-old woman with chronic neuropathic pain, high-frequency repetitive transcranial magnetic stimulation (rTMS) improved her quality of life, anxiety, depression, and walking ability, despite no change in pain intensity.

The results suggest that rTMS may enhance daily functioning in chronic pain patients by influencing brain circuits, indicating its potential therapeutic benefits beyond just pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic impact of motor cortex rTMS in patients with chronic neuropathic pain even in the absence of an analgesic response. A case report. Hodaj, H., Payen, JF., Lefaucheur, JP.[2018]

The conditioned pain modulation (CPM) response may help differentiate between migraine patients and those with other headache types, suggesting its potential role in migraine diagnosis.

The CPM response could also predict treatment outcomes for migraines and is being explored in devices designed for both acute and preventative migraine treatment, indicating its relevance in improving migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harnessing the conditioned pain modulation response in migraine diagnosis, outcome prediction, and treatment-A narrative review. Nahman-Averbuch, H., Callahan, D., Darken, R., et al.[2023]

In a study of 35 healthy volunteers, researchers found that effective conditioned pain modulation (CPM) is linked to stronger connectivity between the periaqueductal grey (PAG) and brain regions involved in pain processing, suggesting a neural basis for pain modulation efficiency.

The results indicate that individuals with better pain modulation may have enhanced functional connectivity in brain areas that help manage pain, which could serve as potential biomarkers for assessing vulnerability or resilience to chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioned pain modulation is associated with heightened connectivity between the periaqueductal grey and cortical regions. Harrison, R., Gandhi, W., van Reekum, CM., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7565989/

Conditioned Pain Modulation Effectiveness - PubMed Central

We aimed to compare the effectiveness of four CPM test paradigms as well as the association of the CPM effect with potential predictors in 72 healthy ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1526590012007365

Conditioned Pain Modulation in Populations With Chronic ...

This review compared the efficacy of conditioned pain modulation between chronic pain and healthy populations. The finding of impaired modulation in the chronic ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05783362

NCT05783362 | Pain Modulation Effectiveness (PME)

Conditioned pain modulation is less efficient in individuals with chronic pain conditions, and it is a predictor for the development of chronic pain. ...

4.

nature.com

nature.com/articles/s41598-024-58079-7

Conditioned pain modulation (CPM) paradigm type affects ...

CPM identifies individuals with faulty pain modulation mechanisms, and if enrolled selectively, can increase the chances of better results, and ...

5.

journals.lww.com

journals.lww.com/pain/fulltext/2016/11000/reliability_of_conditioned_pain_modulation__a.5.aspx

Reliability of conditioned pain modulation: a systematic...

A systematic literature review was undertaken to determine if conditioned pain modulation (CPM) is reliable. Longitudinal, English language observational ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06726018

Exploring Pain Modulation With TMS and Repeated ...

TMS is a non-invasive neurophysiological technique that employs magnetic fields to modulate and measure brain activity. It is particularly valuable in studying ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11856385/

Effects of Repetitive Transcranial Magnetic Stimulation ...

In this study, we investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left upper limb primary motor ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S1388245725003189

Accelerated intermittent theta burst transcranial magnetic ...

We show that active treatment with 36,000 pulses over 4 consecutive days was safe, acceptable and generally well tolerated with only 1 in 5 requiring a lower ...

9.

journals.lww.com

journals.lww.com/painrpts/fulltext/2022/06000/conditioned_pain_modulation_is_associated_with.10.aspx

Conditioned pain modulation is associated with heightened...

We found that CPM was associated with heightened connectivity between the PAG and key regions associated with pain processing and inhibition.

10.

bmjopen.bmj.com

bmjopen.bmj.com/content/7/8/e013080

a protocol for a pilot randomised controlled trial

A mild tingling or itching sensation under the electrodes, fatigue, headache, nausea and insomnia have been reported as potential adverse reactions following ...