Repetitive Transcranial Magnetic Stimulation Therapy in Spinal Cord Injury Related Neuropathic Pain

Efficacy of Repetitive Transcranial Magnetic Stimulation Therapy in Neuropathic Pain Associated With Spinal Cord Injury; Randomized Controlled Trial

The aim of our study is to investigate the effect of different protocols of high-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) therapy added to the rehabilitation program on neuropathic pain,depression, quality of life and quality of sleep compared to each other and placebo group in participants with spinal cord injury.

Study Overview

• Status: Recruiting
• Conditions: Neuropathic Pain; Spinal Cord Injuries
• Intervention / Treatment: Device: High-frequency real-time rTMS DLPF cortex protocol; Device: High-frequency real-time rTMS M1 motor cortex protocol; Device: Sham rTMS Protocol

Detailed Description

Spinal cord injury is a disability that causes the loss of many functions for example motor,sensory and autonomic functions in the body. Neuropathic pain is a common problem in participants with spinal cord injury. Many treatment options have been offered for a debilitating condition that has major negative effects on participant's quality of life but provides limited effects and many secondary effects. There is evidence for neuromodulation techniques to improve many pain conditions, such as neuropathic pain. One innovative method for neuropathic pain management, rTMS, is a non-invasive neuromodulation intervention with a low risk of side effects that works by altering brain activity. While most studies to date have mainly targeted the primary motor cortex (M1), fewer studies have reported analgesic effects after stimulation of other cortical areas such as the dorsolateral prefrontal cortex (DLPFC).

The initial assessment will include answering questionnaires: Brief Pain Inventory, Neuropathic Pain Symptom Inventory(NPSI), International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) self-report version, Patient Catastrophizing Scale(PCS), Beck Depression Inventory,Quality of Life Index Spinal Cord Injury v3 (QLI-SCI), Pain Catastrophizing Scale (PCS),Pittsburgh Sleep Quality Index and previous medication and treatment questionnaires.Participants will be asked to complete the above-mentioned questionnaires post-rTMS treatment and at 2 months after their last rTMS treatment.

TMS Protocol: Participants will undergo high frequency rTMS sessions 5 days a week for 4 weeks (20 treatments total). Daily rTMS sessions will include at a frequency of 10 Hz, treatment intensity will be applied at 120% of the participants resting motor threshold (RMT). A RMT is the minimal intensity required to evoke a motor evoked potential and will be obtained by administering single-pulse TMS to the left motor cortex participant a will be seated in a comfortable chair or their wheelchair for each rTMS session.

Participants with spinal cord injury receiving rTMS in DLPFC or M1 protocol in addition to neurological rehabilitation will be compared with the sham rTMS group in terms of neuropathic pain, sleep quality, depression and quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nuran Eyvaz, MD; Phone Number: +905334262442; Email: eyvaznuran@gmail.com
• Study Contact Backup: Name: Ayşe Kalender, MD; Phone Number: +905389563559; Email: aysebuber007@gmail.com

Study Locations

• Turkey (Türkiye)
  • Afyonkarahisar, Turkey (Türkiye), 0300
    • Recruiting
    • Afyonkarahisar Health Sciences University
    • Contact: Ayşe Kalender, MD; Phone Number: +905389563559; Email: aysebuber007@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Aged 18-75 years Physician-diagnosed spinal cord injury for at least 3-months Neuropathic pain for at least 3-months Pain not attributable to any other conditions

Exclusion Criteria:

• Having an important comorbid disease such as severe heart disease (aortic stenosis, angina, hypertrophic cardiomyopathy, uncontrolled hypertension,arrhythmia, pacemaker)
• Neurodegenerative disease
• Epilepsy
• History of antiepileptic drug use
• Cognitive dysfunction
• Lower extremity peripheral nerve injury
• Increased intracranial pressure or uncontrolled migraine
• Infection on the skin in the application area.
• Having a brain lesion or a history of drug use that will affect the seizure threshold.

Any TMS-related contraindications, for example:

• Pacemaker
• Metallic implant
• Previous seizure
• Psychiatric disorders (excluding depression and anxiety)
• Malignancy
• Current pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First Group; High-frequency real-time rTMS protocol It was planned to apply the dorsolateral prefrontal cortex daily at a frequency of 10 Hz for 20 sessions.	Device: High-frequency real-time rTMS DLPF cortex protocol; It was planned to apply the dorsolateral prefrontal cortex daily for 20 sessions.Along with the daily rTMS session, participants will continue to use the medications in the medical treatment at the same effective dose and no dose changes will be made during the treatment.
Experimental: Second Group; High-frequency real-time rTMS protocol It was planned to apply the M1 motor cortex daily at a frequency of 10 Hz for 20 sessions.	Device: High-frequency real-time rTMS M1 motor cortex protocol; It was planned to apply the M1 motor cortex daily for 20 sessions.Along with the daily rTMS session, participants will continue to use the medications in the medical treatment at the same effective dose and no dose changes will be made during the treatment.
Sham Comparator: Third Group; Sham rTMS Protocol It was planned to apply daily sham rTMS for 20 sessions.	Device: Sham rTMS Protocol; It was planned to apply the daily for 20 sessions.Along with the daily rTMS session, participants will continue to use the medications in the medical treatment at the same effective dose and no dose changes will be made during the treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Brief Pain Inventory-Short Form (BPI-SF) at 1. and 2 months.	The Brief Pain Inventory Short Form (SPI-SF) is designed to examine pain in terms of sensory (pain intensity) and impact on daily functioning. The BPI-SF consists of two parts. The first part assesses the severity of worst, mildest, average and momentary pain using a numerical rating scale (NRS; 0-10). A response of 0 indicates "no pain at all" and a response of 10 indicates "the most severe pain imaginable". The second part consists of seven questions assessing how much pain affects daily functioning, including general activity and enjoyment of life. A response of 0 indicates "not at all affected" and a response of 10 indicates "completely affected". The total score ranges from 0-70. Higher scores indicate worsening symptoms.	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Beck Depression Inventory (BDI) Scores at 1. and 2 months.	Validated measure of clinical depression symptoms to quantify and track mood over time. Scores index depression severity and range from 0-63: 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.Total score is 63. Higher scores indicates depressive mood.	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.
Change in the Patient's Global Impression of Change (PGIC) observed at 1 month and 2 months.	Standardized assessment to assess participants overall impression of improvement. Scores range from 1 to 7, with 1 representing "no change" and 7 representing "a great deal better"	To be assessed after rTMS treatment (1-month) and 2-months after rTMS treatment.
Change from baseline Pittsburgh Sleep Quality Index (PSQI) at 1. and 2 months.	The Pittsburgh Sleep Quality Index (PSQI) is an 18-item questionnaire that assesses sleep quality and disturbances over the past month. The investigators will use the 3-factor scoring, which has been shown to have superior psychometric properties. The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.
Change from baseline International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) self-report version at 1. and 2 months.	Pain profile, including location, intensity, and interference over the past 7 days will be assessed using the ISCIPBDS self-report tool. All variables are rated on a scale ranging from 0 (no pain at all) to 10(the most severe pain imaginable).Higher scores indicate higher pain intensity.	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.
Change from baseline Quality of Life Index Spinal Cord Injury version (QLI-SCI) at 1. and 2 months.	Quality of life and satisfaction with aspects of quality of life will be assessed using the QLI-SCI instrument. This questionnaire focuses on the categories of health and functioning, social and economic, psychological/spiritual, and family. All variables are rated on a scale ranging from 0 (completely dissatisfied) to 10(completely satisfied) with a total of 40 points. Higher scores indicates better quality of life.	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.
Change from baseline Pain Catastrophizing Scale (PCS) at 1. and 2 months.	Pain experience will be assessed using the PCS. Participants are asked to rate how much they agree with the listed thoughts and feelings they may have when experiencing pain from 0 (not at all) to 4 (all the time). The total score ranges from 0-52. Higher scores indicate increase level of catastrophizing.	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.
Change from baseline Neuropathic Pain Symptom Inventory (NPSI) at 1.and 2 months.	An 11-point NRS assess average neuropathic pain severity over the last week. The scale ranged from 0 to 10, with 0 representing "no pain" and 10 representing "the most intense pain imaginable". The NPSI is comprised of five subscales: burning spontaneous pain (burning), pressing spontaneous pain (pressing), paroxysmal pain (paroxysmal), evoked pain (evoked), and paresthesia/dysesthesia. Full scale from 0-10, with higher score indicating more symptom.	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.
Change from baseline Modified Ashworth Scale (MAS) at 1. and 2 months.	Modified Ashworth Scale (MAS) will measure spasticity in the limbs. Higher scores represent spasticity or increased resistance to passive movement. All variables are rated on a scale ranging from 0 to 5: 0 means no increase in muscle tone (better outcome) and 5 means rigid (worse outcome).	To be assessed at baseline, after rTMS treatment (1-month) and 2-months after rTMS treatment.

Collaborators and Investigators

• Sponsor: Afyonkarahisar Health Sciences University
• Investigators: Principal Investigator: Nuran Eyvaz, MD, Afyonkarahisar Health Sciences University

Publications and helpful links

General Publications

• Saleh C, Ilia TS, Jaszczuk P, Hund-Georgiadis M, Walter A. Is transcranial magnetic stimulation as treatment for neuropathic pain in patients with spinal cord injury efficient? A systematic review. Neurol Sci. 2022 May;43(5):3007-3018. doi: 10.1007/s10072-022-05978-0. Epub 2022 Mar 3.
• Attal N, Poindessous-Jazat F, De Chauvigny E, Quesada C, Mhalla A, Ayache SS, Fermanian C, Nizard J, Peyron R, Lefaucheur JP, Bouhassira D. Repetitive transcranial magnetic stimulation for neuropathic pain: a randomized multicentre sham-controlled trial. Brain. 2021 Dec 16;144(11):3328-3339. doi: 10.1093/brain/awab208.
• Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: December 5, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Actual): December 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Spinal Cord Injury; Neuropathic Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neuralgia; Spinal Cord Injuries
• Other Study ID Numbers: TMSSCINP

Drug and device information, study documents

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