Improvement the Anti-migraine Treatment Efficacy by Tailoring the Drug to Individual's Pain Modulation Profile

Study Overview
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Brief Summary
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To delineate brain mechanisms that subserve endogenous analgesic (EA) in the healthy state. To identify alterations in mechanisms supporting EA in chronic pain (migraine) and their therapeutic relevance.

Detailed Description
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The proposed research will use psychophysics and multiparametric MRI to (i) delineate the brain mechanisms that subserve and regulate endogenous analgesia (EA)in the healthy state and (ii) to identify alterations in mechanisms supporting EA in chronic pain and their therapeutic relevance. In both healthy subjects and chronic pain patients, EA will be probed using the DNIC (diffuse noxious inhibitory controls) and offset analgesia paradigms. Functional MRI will examine activation of brainstem mechanisms important in EA, while both functional and structural connectivity analyses will assess the regulation of these brainstem mechanisms by cerebral cortical regions involved in attention and affect. One pathological painful condition, migraine, will be examined since it allows changes in EA associated with chronic pain to be investigated between episodes of pain. Finally, EA and EA associated structural and functional parameters will be used to predict the efficacy of one compound, amitriptyline, to treat migraine in individual patients. Taken together, the proposed research will provide substantial insights into basic mechanisms supporting and regulating EA and can provide a foundation for mechanism-based individualized choice of therapy that may benefit all chronic pain patients.

Conditions
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Pain

Intervention / Treatment
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* Drug: duloxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy females migaine females ages 18-50 for migraineurs: >4 attacks/month Exclusion Criteria: any migraine preventive treatment received during last 3 months or prior treatment with amytriptiline other chronic pain conditions psychiatric, other neurological diseases, language barrier or cognitive dysfunction Patients and controls will be asked to withdraw from any pain-relieving medications for 24 hours before the testing. The tests will be performed interictally atleast 2 days after the last attack.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>migraine patients to receive placebo treatment | Drug: duloxetine<br>* duloxetine 60mg once a day for 5 weeks<br>|
| Active Comparator: duloxetine<br>migraine patients to receive duloxetine | Drug: duloxetine<br>* duloxetine 60mg once a day for 5 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distinguish between two endogenous pain modulation mechanisms |  | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To charcterize functional and structural neuroanatomical correlates of pain modulation profile and it's relevance for predicting the duloxetine efficacy in migraine |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endogenous pain modulation, migraine, fMRI, duloxetine, preventive migraine treatment