Combining fMRI and tDCS in Neuropathic Pain

Combining Functional Magnetic Resonance Imaging and Transcranial Direct Current Stimulation to Investigate Pain-related Brain Networks in Patients With Neuropathic Pain

The proposed project aims to explore possible neuromodulatory effects of transcranial direct current stimulation (tDCS) on neuropathic pain caused by peripheral neuropathy. tDCS will be performed through an MRI-compatible stimulation setting during functional magnetic resonance imaging (fMRI) scanning. The stimulation target of tDCS will be the primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC). We expect that results from the current project will advance the understanding of neuromodulatory mechanisms of tDCS and facilitate the development of treatment strategies for patients with neuropathic pain.

Study Overview

• Status: Recruiting
• Conditions: Neuropathic Pain
• Intervention / Treatment: Device: transcranial direct current stimulation

Detailed Description

Neuropathic pain is the most excruciating symptom in peripheral neuropathy such as diabetic or chemotherapy-induced neuropathy. Management of neuropathic pain is a challenging clinical problem because only less than 50% patients are responsive to pharmacological treatment. Neuropathic pain is naturally considered as a direct consequence of peripheral nerve injury that induces hypersensitivity or ectopic activities in nociceptive nerve terminals. Nevertheless, maladaptive changes in the pain-related networks of the brain also play a crucial role in the generation, amplification, and drug-resistance of neuropathic pain. The proposed project aims to explore possible neuromodulatory effects of transcranial direct current stimulation (tDCS) on neuropathic pain caused by peripheral neuropathy. tDCS is a non-invasive stimulation technique that delivers a low-intensity current into the brain to modulate the synaptic plasticity of cortical neurons. To investigate the instantaneous effects of tDCS, tDCS will be performed through an MRI-compatible stimulation setting during functional magnetic resonance imaging (fMRI) scanning. The stimulation target of tDCS will be the primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC). This simultaneous tDCS-fMRI approach will enable us to (1) identify the neural substrates of neuropathic pain that could be modulated by neurostimulation, (2) to characterize the spatial patterns of functional hemodynamic brain responses following tDCS, and (3) to assess changes in cortical excitability and neuroplasticity associated with pain perception after non-invasive brain stimulation. We expect that results from the current project will advance the understanding of neuromodulatory mechanisms of tDCS and facilitate the development of treatment strategies for patients with neuropathic pain.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sung-Tsang Hsieh, MD, PhD; Phone Number: 88182 (886)-2- 2-2312-3456; Email: shsieh@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 112
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Sung-Tsang Hsieh; Phone Number: 88182 (886)-2- 2-2312-3456; Email: shsieh@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1. Age 20 or older and 90 or younger. 2. Ability to give informed consent 3. Neuropathic pain and/or nonpainful sensory symptoms resulted from I or II I. Peripheral neuropathy confirmed by clinical symptoms nerve conduction study, autonomic function test, quantitative sensory test, or skin biopsy.

II. Stroke involving somatosensory pathway confirmed by neuroimage 4. Agree not to take caffeine, alcohol, tea and drugs with significant nervous system effects for 48 hours before each study session.

Exclusion Criteria:

• 1. Presence of sever systemic diseases, including severe ischemic heart disease or congestive heart failure (left ventricular ejection fraction < 30%), severe lung diseases with dyspnea, severe generalized edema, and systemic infection 2. Presence of major neurological disorders, including brain tumor, head trauma and infection or inflammation of nervous system.

  3. Presence of major depression or any major mental disorders 4. Presence of a cardiac pacemaker, brain stimulator, aneurysm clips or metal implants in the head, unless these devices are certified to be MRI-compatible 5. Pregnancy 6. Claustrophobia or any other contraindications to MRI 7. Inability to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tDCS stimulation; 2-milliamp stimulation for 5~15 min	Device: transcranial direct current stimulation; 2-milliamp stimulation for 5~15 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain functional connectivity changes	changes in brain functional connectivity after tDCS, assessed using functional MRI	5 days after stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity of neuropathic pain	reduction of neuropathic pain assessed using visual analog scale	5 days after stimulation

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2023
• Primary Completion (Estimated): September 11, 2030
• Study Completion (Estimated): September 11, 2030

Study Registration Dates

• First Submitted: January 15, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Estimated): February 1, 2024

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia
• Other Study ID Numbers: 202012283RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No