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

40 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Conditioned Pain Modulation (CPM) for pain modulation?

Research suggests that Conditioned Pain Modulation (CPM) can predict how well someone might respond to pain treatments, and it involves brain areas that help control pain. Additionally, repetitive transcranial magnetic stimulation (rTMS), a similar treatment, has shown benefits for chronic pain, indicating potential effectiveness for CPM. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) generally safe for humans?

Research suggests that transcranial magnetic stimulation (TMS) is generally safe for humans, as it is a minimally invasive brain stimulation technique used for pain management. However, the safety can depend on the specific device settings and individual responses, so it's important to follow guidelines and consult with healthcare professionals. ^{1 2 4 6 7}

How is the treatment Conditioned Pain Modulation (CPM) different from other treatments for pain?

Conditioned Pain Modulation (CPM) is unique because it uses a natural process where one painful stimulus reduces the perception of another, leveraging the body's own pain control mechanisms rather than relying on medications. This approach is different from typical pain treatments that often involve drugs or direct interventions. ^{1 2 8 9 10}

What is the purpose of this trial?

Conditioned pain modulation (CPM) is the behavioral measure of diffuse noxious inhibitory control (DNIC), an endogenous pain inhibitory pathway in which pain inhibits pain. CPM is less efficient in individuals with chronic pain conditions, and it is a predictor for the development of chronic pain. Continuous stimulation of central/cortical mechanisms through engaging CPM might alter pain processing and improve pain inhibition. Transcranial Magnetic Stimulation (TMS) is a valuable tool for assessing how effectively the brain's central and cortical mechanisms engage in pain inhibition, particularly through pathways like CPM. While alterations in cortical excitability related to analgesic-induced pain inhibition have been documented, the effects of continuous stimulation of central pain pathways, along with the mediating influence of psychosocial factors, remain underexplored. This study aims to investigate the central pain modulatory mechanisms, as assessed by CPM, and cortical excitability, as measured by TMS, in healthy participants. Additionally, the study will evaluate the impact of sociocultural factors, including ethnic identity, optimism, resilience, perceived stress, and marginalization, on the magnitude and efficiency of CPM responses. The successful completion of this research will determine how cortical excitability changes due to training and whether these changes are mediated by psychosocial factors.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Priyanka Rana, PT, MPT, PhD

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Conditioned pain modulation is associated with heightened connectivity between the periaqueductal grey and cortical regions. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Neurophysiological oscillatory markers of hypoalgesia in conditioned pain modulation. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Prediction of duloxetine efficacy in addition to self-management in painful temporomandibular disorders: A randomised, placebo-controlled clinical trial. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Factors Associated with Low Inter-Session Reliability of Conditioned Pain Modulation in Older People with or Without Chronic Musculoskeletal Pain. [2023]

5. France 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. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Considerations for multi-centre conditioned pain modulation (CPM) research; an investigation of the inter-rater reliability, level of agreement and confounders for the Achilles tendon and Triceps Surae. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A randomized, controlled investigation of motor cortex transcranial magnetic stimulation (TMS) effects on quantitative sensory measures in healthy adults: evaluation of TMS device parameters. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Comparison of five conditioned pain modulation paradigms and influencing personal factors in healthy adults. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Age does not affect sex effect of conditioned pain modulation of pressure and thermal pain across 2 conditioning stimuli. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Harnessing the conditioned pain modulation response in migraine diagnosis, outcome prediction, and treatment-A narrative review. [2023]