An Exploration of the Neuroplasticity of Endogenous Analgesia in Health and Chronic Pain

Integration of Neuroimaging and Transcranial Magnetic Stimulation: an Exploration of the Neuroplasticity of Endogenous Analgesia in Health and Chronic Pain

Transcranial magnetic stimulation (TMS) is a neurophysiological tool for studying cortical functions, and in addition, has an analgesic therapeutic effect whose underlying mechanism is unknown. The proposed research will use TMS in conjunction with brain imaging and electrophysiology to examine cortical plasticity and connectivity modifications induced by repetitive TMS (rTMS) targeted to affect cortical regions associated with endogenous analgesia (EA). This will be carried out in both healthy and chronic pain (fibromyalgia) states. rTMS analgesic intervention, targeted to the motor cortex (M1) will be preceded and followed by structural and functional magnetic resonance imaging (fMRI), and Diffusion Tensor Imaging (DTI). This will be done in order to examine alterations of cortical and brainstem mechanisms involved in EA and to investigate connectivity changes between cortical and sub-cortical regions of the EA networks. The latter as well as EA efficiency and pain-related personality variables will be used to assess individual differences in neuroplasticity within the EA systems in both healthy subjects and chronic pain patients.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Device: active repeated transcranial magnetic stimulation; Device: 'sham' repeated transcranial magnetic stimulation

Detailed Description

Transcranial magnetic stimulation (TMS) is a neurophysiological tool for studying cortical functions, and in addition, has an analgesic therapeutic effect whose underlying mechanism is unknown. The proposed research will use TMS in conjunction with brain imaging and electrophysiology to examine cortical plasticity and connectivity modifications induced by repetitive TMS (rTMS) targeted to affect cortical regions associated with endogenous analgesia (EA). This will be carried out in both healthy and chronic pain (fibromyalgia) states. rTMS analgesic intervention, targeted to the motor cortex (M1) will be preceded and followed by structural and functional magnetic resonance imaging (fMRI), and Diffusion Tensor Imaging (DTI). This will be done in order to examine alterations of cortical and brainstem mechanisms involved in EA and to investigate connectivity changes between cortical and sub-cortical regions of the EA networks. The latter as well as EA efficiency and pain-related personality variables will be used to assess individual differences in neuroplasticity within the EA systems in both healthy subjects and chronic pain patients .

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• a prior FMS diagnosis by a rheumatologist or pain specialist based on American College of Rheumatology (ACR) preliminary diagnostic criteria for fibromyalgia
• healthy subjects - no pain/psychiatry/neurological diseases

Exclusion Criteria:

• other chronic pain, psychiatric or neurological diseases. All will be asked to withdraw from any pain-relieving medications for 24h before the testing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active rTMS; active repeated transcranial magnetic stimulation over primary motor cortex along 5-10 daily sessions	Device: active repeated transcranial magnetic stimulation; ten daily sessions with active 10Hz 20 min-long stimulation over the primary motor cortex
Sham Comparator: 'sham' rTMS; 'sham' repeated transcranial magnetic stimulation over primary motor cortex along 5-10 daily sessions	Device: 'sham' repeated transcranial magnetic stimulation; ten daily sessions with 'sham' 10Hz 20 min-long stimulation over the primary motor cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rTMS-induced change in fibromyalgia pain level	Fibromyalgia pain level will be measured using the numerical pain scale; the patients will be asked to rate their mean pain level over the last 5 days	through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment-induced changes of white-matter connectivity of the brain	White-matter connectivity will be measured using the method of diffusion tensor imaging of the brain	through study completion, an average of 2 year

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Investigators: Principal Investigator: David Yarnitsky, MD, Prof, Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2015
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: October 6, 2015
• First Submitted That Met QC Criteria: October 8, 2015
• First Posted (Estimate): October 9, 2015

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Chronic Pain; Fibromyalgia
• Other Study ID Numbers: 0106-15_CTIL