Factors Influencing Migraine in Adolescents

Overseen By Alana McMichael, MA

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Pain, Psychiatric

Disqualifiers: Chronic pain, Neurological, Psychiatric, others

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

Compensation: Varies

Number of Visits: 4

250 Participants Needed

Trial Summary

What is the purpose of this trial?

Aim 1. To identify psychophysical and neural factors predicting migraine onset in adolescents Aim 2a. To determine hormonal, psychophysical, and neural changes associated with migraine onset. Aim 2b. To identify the temporal relationships between hormonal, psychophysical, and neural changes preceding vs. following migraine onset. Aim 3. To identify psychophysical and neural factors predicting migraine prognosis in adolescents with migraine.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but if you are on preventative treatment for migraines, it must be stable with no changes in the last 6 months. Regular use of pain or psychiatric medications may exclude you from participating.

What data supports the effectiveness of the treatment conditioned pain modulation (CPM) for migraines in adolescents?

Research suggests that conditioned pain modulation (CPM) can be used to predict responses to pain interventions and may help in understanding pain mechanisms in migraine sufferers, although specific effectiveness data for adolescents is not provided. ^{1 2 3 4 5}

Is conditioned pain modulation (CPM) safe for humans?

The research on conditioned pain modulation (CPM) primarily focuses on its use as a tool to measure pain response and predict treatment outcomes, rather than directly addressing safety. However, CPM is generally used in controlled experimental settings with healthy adults, suggesting it is considered safe for such purposes. ^{1 2 3 6 7}

How does this treatment for adolescent migraines differ from other treatments?

This treatment focuses on understanding and potentially utilizing the conditioned pain modulation (CPM) response, which is a mechanism that can influence how pain is processed in the body. Unlike standard treatments that may focus on medication, this approach looks at the body's natural ability to modulate pain, which could offer a novel way to predict and treat migraines in adolescents. ^{1 8 9 10 11}

Research Team

Hadas Nahman-Averbuch, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for boys and girls aged 10-13, with or without a family history of migraines. It includes those who have not been diagnosed with migraines but show symptoms, as well as those who've had migraines for over six months. Participants should not be on new preventative treatments.

Inclusion Criteria

I am 10-13 years old, do not have migraines, but have a relative with migraines.

I am 10-13 years old with migraines for over 6 months and no recent change in my preventative treatment.

Exclusion Criteria

Healthy group: Diagnosis of any chronic pain syndrome, Diagnosis of a neurological, developmental, pubertal, or psychiatric disorder, Taking pain or psychiatric medications regularly, Having an MRI contraindication such as metal in the body or claustrophobia, Not able to understand and communicate in English

I have migraines but no other chronic pain, mental health issues, or MRI issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person or virtual)

Baseline Study Visit

Participants undergo MRI scan, sensory testing, blood draw, and surveys to determine migraine diagnosis

1 day

1 visit (in-person)

Monthly Surveys

Participants complete short online monthly surveys for 2 years about headache frequency and severity

2 years

Monthly online surveys

Follow-up Study Visits

Participants return for follow-up visits after 1 and 2 years, which may include MRI, sensory testing, and surveys

1 day per visit

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Conditioned pain modulation (CPM) efficiency
• Hormonal assessment
• Migraine-related measures
• MRI
• Neural assessments
• Pain ratings
• Pressure pain thresholds (PPT)
• Pressure stimuli
• Pubertal status
• Thermal Stimuli

Trial Overview The study aims to understand factors predicting migraine onset and prognosis in adolescents by assessing pain responses, hormonal levels, brain activity through MRI scans, and how puberty status might influence these factors.

Participant Groups

Group I: No Family History of Migraine Experimental Treatment 10 Interventions

This group does not have a first or second degree relative diagnosed with migraine.

Group II: Family History of Migraine Experimental Treatment 10 Interventions

This group has a first degree relative diagnosed with migraine.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

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]

The study found that a tonic heat stimulus protocol produced a significantly larger conditioned pain modulation (CPM) effect compared to a phasic heat stimulus protocol, suggesting it may be a more effective method for measuring endogenous analgesia.

Despite the tonic protocol showing better reliability, both methods exhibited large variability in individual responses, indicating caution is needed when using CPM as a biomarker for clinical decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A tonic heat test stimulus yields a larger and more reliable conditioned pain modulation effect compared to a phasic heat test stimulus. Lie, MU., Matre, D., Hansson, P., et al.[2022]

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 study involving 39 episodic migraineurs and 35 controls, both groups showed similar levels of pain modulation efficiency, indicating that migraineurs do not have a significant impairment in their ability to modulate pain compared to healthy individuals.

While controls demonstrated a significant conditioned pain modulation effect, migraineurs did not, suggesting that the specific pain modulation methods used may influence outcomes and that migraineurs may have varied responses to different pain modulation paradigms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do patients with interictal migraine modulate pain differently from healthy controls? A psychophysical and brain imaging study. Kisler, LB., Granovsky, Y., Coghill, RC., et al.[2021]

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]

The newly developed single test-stimulus conditioned pain modulation (STS-CPM) protocol demonstrated superior reliability in measuring pain inhibition compared to other methods, with an intraclass correlation coefficient (ICC) of 0.59.

Using a larger contact size for the conditioning stimulus and a single test stimulus improved the reliability of pain assessments, suggesting that these factors are important for enhancing the clinical utility of pain modulation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPM Test-Retest Reliability: "Standard" vs "Single Test-Stimulus" Protocols. Granovsky, Y., Miller-Barmak, A., Goldstein, O., et al.[2022]

In a study involving healthy adults, conditioned pain modulation (CPM) was shown to be primarily influenced by sensory input rather than cognitive factors like evaluation or imagery, indicating that the underlying mechanisms of CPM are likely subcortical.

The research demonstrated that while cognitive evaluations could increase pain ratings, they did not significantly affect the magnitude of CPM, reinforcing the idea that CPM is a reliable method for studying the body's natural pain relief processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus. Bernaba, M., Johnson, KA., Kong, JT., et al.[2020]

In a study of 19 adolescents with migraine compared to 49 healthy controls, it was found that those with migraine reported lower pain intensity ratings in response to heat stimuli, indicating a difference in pain sensitivity among groups.

Despite these differences in pain sensitivity, both adolescents with migraine and healthy controls exhibited similar capabilities for inhibitory pain modulation, suggesting that the mechanism of pain inhibition may not be impaired in youth with migraine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased pain sensitivity but normal pain modulation in adolescents with migraine. Nahman-Averbuch, H., Leon, E., Hunter, BM., et al.[2021]

The study involving 62 healthy participants found that the reliability of conditioned pain modulation (CPM) and offset analgesia was consistent across sexes and menstrual cycle phases, suggesting that these measures are stable regardless of hormonal fluctuations.

While the magnitude of pain modulation effects showed some weak influence from sex and testosterone levels, the overall findings indicate that individual experimental parameters play a more significant role in pain modulation than participant characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioned pain modulation and offset analgesia: Influence of sex, sex hormone levels and menstrual cycle on the magnitude and retest reliability in healthy participants. Vollert, J., Trewartha, N., Kemkowski, D., et al.[2022]

Adolescent girls with chronic pain showed significantly less effective pain inhibitory mechanisms, specifically conditioned pain modulation (CPM) and exercise-induced analgesia (EIA), compared to healthy peers, indicating a potential dysfunction in their ability to manage pain.

In this study involving 41 participants (25 healthy and 16 with chronic pain), the chronic pain group did not experience reduced pain perception after intense pain or exercise, suggesting that their natural pain relief systems are impaired.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced endogenous pain inhibition in adolescent girls with chronic pain. Chrétien, R., Lavoie, S., Chalaye, P., et al.[2019]

Conditioned pain modulation (CPM) has been under-researched in pediatric populations, with only twelve studies identified that specifically focus on children and adolescents, highlighting a gap in understanding pain processing in younger individuals.

Deficiencies in descending pain pathways may contribute to chronic pain conditions in children, suggesting that CPM could be a valuable tool for clinicians and researchers to tailor treatments for pediatric pain syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current methodological approaches in conditioned pain modulation assessment in pediatrics. Hwang, PS., Ma, ML., Spiegelberg, N., et al.[2020]

References

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

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

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

A tonic heat test stimulus yields a larger and more reliable conditioned pain modulation effect compared to a phasic heat test stimulus. [2022]

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

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

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

Do patients with interictal migraine modulate pain differently from healthy controls? A psychophysical and brain imaging study. [2021]

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

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

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

CPM Test-Retest Reliability: "Standard" vs "Single Test-Stimulus" Protocols. [2022]

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

Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus. [2020]

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

Increased pain sensitivity but normal pain modulation in adolescents with migraine. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Conditioned pain modulation and offset analgesia: Influence of sex, sex hormone levels and menstrual cycle on the magnitude and retest reliability in healthy participants. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Reduced endogenous pain inhibition in adolescent girls with chronic pain. [2019]

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

Current methodological approaches in conditioned pain modulation assessment in pediatrics. [2020]