Effects of Prolonged Continuous Theta Burst Stimulation on Pain and Neural Excitability

The Second Affiliated Hospital Zhejiang University School od Medicine

Numerous studies have confirmed the analgesic effect of M1-rTMS on both induced pain and various chronic pains and subsequently found that pcTBS is more time-efficient and can produce the same or even stronger analgesic effect, however, its study in pathological pain h has not been thoroughly investigated. Due to the dynamic nature of the injury sensory system, pain also exhibits a dynamic process, but there is a lack of specific methods or biomarkers to document this process. Surface electromyography (EMG) is a common technique used in rTMS studies to reflect changes in cortical excitability. In turn, both pain and rTMS interventions can cause changes and thus can be used as a potential biomarker to predict pain onset and progression. In addition, the number of sessions of rTMS treatment is an important factor influencing the analgesic effect of rTMS. In summary, this study intends to explore the best pain predictor by using a capsaicin-induced pain model in healthy volunteers, monitor the dynamic changes of cortical excitability index and VAS score before and after pcTBS intervention, and also verify the relationship between the number of pcTBS treatments and analgesic effect, to provide a new strategy for the prevention and treatment of neuropathic pain.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; pcTBS
• Intervention / Treatment: Device: pcTBS of M1; Device: SHAM stimulation

Detailed Description

This study was a prospective, single-blind, sham-controlled, crossover-design trial. Each subject was randomized to receive 3 sessions of rTMS intervention, consisting of 2 consecutive pcTBS stimulations and 1 sham stimulation, with no less than 3 days between each session. The pain was induced by applying capsaicin to the dorsum t of the right hand and recording electromyographic (EMG) signals with surface electrodes on the right first interosseous muscle. Subjects received M1- pcTBS or sham stimulation (Sham) intervention at 40 minutes of capsaicin application (T40). Subjects' cortical excitability was measured at 5-minute intervals at baseline, 40 minutes after capsaicin application and pcTBS intervention, and pain perception was assessed at 10-minute intervals (each assessment to be performed at the end of the measurement).

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: min yan, prof.; Email: zryanmin@zju.edu.cn
• Study Contact Backup: Name: chaomin wu, doctor; Phone Number: 15990027747; Email: cmwu@zju.edu.cn

Study Locations

• China
  • Hangzhou, China
    • The second affiliated hospital of Zhejiang University hangzhou
    • Contact: MIN YAN; Email: zryanmin@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1) 18-65 years of age; 2) physical and mental health, free of chronic pain (through interviews and McGill questionnaires); 3) Right-handed

Exclusion Criteria:

1) inability to receive TMS interventions (e.g. pacemaker); 2) mental illness or suicidal tendencies; 3) history of previous seizures/epilepsy; 4) previous craniocerebral surgery for stroke or other reasons; 5) drug/substance dependence; 6) Inability to sit upright to cooperate with assessment and treatment; 7) Pregnancy or planning to become pregnant within half a year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: SHAM stimulation; The Sham stimulation was delivered using the same protocol, with the coil being orientated at 90° to the scalp so that the magnetic field would be delivered away from the scal	Device: SHAM stimulation; The Sham stimulation was delivered using the same pcTBS protocol, with the coil being flipped 90◦to the scalp so that the magnetic field would be delivered away from the scalp
Experimental: Active stimulation of M1; pcTBS was administered to the left M1 at 80% resting motor threshold (RMT), consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline.	Device: pcTBS of M1; Prolonged continuous theta-burst stimulation (pcTBS) was administered to the left M1 at 80% RMT, consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of pain intensity	pain intensity on a 10-cm visual analogue scale (VAS) extending from 0 (no pain) to 100 (maximal pain possible) at baseline and posttreatment of pcTBS stimulation	through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor-evoked potential (MEP)	Corticospinal excitability was measured with MEP at rest of the first dorsal interosseous (FDI) muscle, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward)	through study completion, an average of 6 months
Cortical silent period (CSP)	Corticospinal excitability will be measured with CSP during a sustained voluntary FDI muscle contraction, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward)	through study completion, an average of 6 months
pain intensity after two sessions of pcTBS	pain intensity on a 10-cm visual analogue scale (VAS) extending from 0 (no pain) to 100 (maximal pain possible) after two sessions of pcTBS	through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: min yan, prof., The second affiliated hospital of Zhejiang University hangzhou

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2023-0276

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