Molecular and Functional PET-fMRI Measures of Analgesia in Migraine

N/ACompletedNCT01970943

Massachusetts General Hospital23 enrolled

Overview

The placebo effect is a phenomenon that has experienced major advances of its understanding in the last decade. However, mechanisms of placebo analgesia in chronic pain patients have yet to be compared to healthy subjects. The investigators study aims to investigate the magnitude of placebo response and related opioid release in patients that suffer from episodic migraines as compared to healthy controls. In particular, the investigators are looking to map brain activity during placebo analgesia using modern brain imaging techniques such as functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET). The investigators hypothesis is that placebo response and the availability of opioid receptors is reduced in chronic migraine patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Migraine Healthy

Interventions

Eligibility

Sex: ALLMin age: 21 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Migraine patients with aura with acute episodic migraine meeting the IHS Classification ICHD-II criteria, 3-14 migraines per month. * History of episodic migraine for at least 3 years * Ages 21-50 * Male or Female * Right Handed Matched healthy subjects will also be recruited. Exclusion Criteria: * Other significant disease (systemic or CNS) * Pregnancy * Claustrophobia * Weight \>235 lbs (limit of MRI table) * Significant drug including alcohol history (\> 7 glasses of alcohol per week) * Beck Depression Inventory II (BDI-II) score \> 25 (moderate to severe depression) * Any metal implants incompatible with MRI (including dental bridges, crowns, retainers, orthodontic devices e.g. braces, IUDs, aneurysm clips or other devices, tattoos containing metallic ink, cardiac pacemakers, prosthetic hear valves, other prostheses, neurostimulator devices, implanted infusion pumps, exposure to shrapnel or metal filings, cochlear implants, etc.) * Previous significant research related exposure to ionizing radiation. * History of allergy or adverse reaction to opioids * Significant medical history of such as seizure disorder, diabetes, alcoholism, cardiac disease including coronary artery disease, psychiatric problems; drug addiction, respiratory problems, liver disease, etc. * Positive drug of abuse screen (excluding medications currently prescribed for their clinical condition, e.g. opioids, benzodiazepines, etc.) * Patients with migraine \<72 hours prior to the experiments will not be included to ensure inter-ictal state. * Opioids or preventative medication such as topiramate, SSRIs etc.

Outcomes

Primary Outcomes

Visual Analogue Scale (VAS) 0-10 Pain Rating

This study will investigate how placebo may reduce experimental pain induced by contact heat. Patients rate heat stimulus intensity on a 0-10 scale, where 0 is no pain, and 10 is most intense pain possible. Data is reported to the placebo condition. The Visual Analogue Scale (VAS) consists of a straight line with the endpoints defining extreme limits such as 'no pain at all' and 'most intense pain possible'. The patient is asked to mark his pain level on the line between the two endpoints.

Time frame: 1 day

Secondary Outcomes

Pain Anticipation fMRI BOLD Signal

We imaged the subjects under an MRI scan. All data was collected on a Siemens 3 Tesla MR scanner using a PETcompatible eight-channel head coil. Structural T1 weighted MPRAGE Functional scans were preprocessed using slice timing correction, realignment, normalization, and smoothing (8 mm FWHM Gaussian filter), using SPM12. In each condition (placebo \& no drug) subjects underwent four sets of pain anticipation at high and low temperatures (somatosensory control condition). The stimuli were modeled as boxcar time series, with additional regressors for temperature ramp-up, ramp-down, pain rating sequence, and six motion regressors.data were collected for each of the two PET-MR scans. Contrasts analyzed included pain anticipation. The values for the 8 sets of anticipation, for both the migraine and the healthy group are combined

Time frame: 1 day

Pain Stimulation fMRI BOLD Signal

We imaged the subjects under an MRI scan. All data was collected on a Siemens 3 Tesla MR scanner using a PETcompatible eight-channel head coil. Structural T1 weighted MPRAGE Functional scans were preprocessed using slice timing correction, realignment, normalization, and smoothing (8 mm FWHM Gaussian filter), using SPM12. In each condition (placebo \& no drug) subjects underwent four sets of pain stimulation at high and low temperatures (somatosensory control condition). The stimuli were modeled as boxcar time series, with additional regressors for temperature ramp-up, ramp-down, pain rating sequence, and six motion regressors.data were collected for each of the two PET-MR scans. Contrasts analyzed included pain stimulation. The values for the 8 sets of stimulation, for both the migraine and the healthy group are combined

Time frame: 1 day

PET Diprenorphine

We sought to find if endogenous opioid levels and endogenous opioid release induced by placebo administration differentiates between the no intervention first, then placebo group compared to the placebo first, then no intervention group in migraine patients.

Time frame: 1 day

Molecular and Functional PET-fMRI Measures of Analgesia in Migraine

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes