1. 2024;27;E589-E595Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex for Phantom Limb Pain
   Randomized Controlled Trial
   Deepanshu Vats, MSc, Renu Bhatia, MD, Samreen Fatima, MSc, Rajkumar Yadav, MD, Sushma Sagar, MS, Nida Mir, MPT, Maroof A. Khan, MD, and Akanksha Singh, MD.

BACKGROUND: Phantom limb pain (PLP) is a prevalent and distressing occurrence in 60-80% of individuals who have undergone amputations. Recent research underscores the significance of maladaptive cortical plasticity in the genesis of PLP, emphasizing the importance of targeting cortical areas for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive tool for cortical stimulation, demonstrates effectiveness in treating various chronic pain conditions of neuropathic origin. Nevertheless, there exists a limited body of research investigating the application of rTMS as a therapeutic intervention specifically for managing PLP. Notably, the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in central pain processing, suggesting its potential as a key therapeutic target in PLP treatment. There is a lack of adequate data regarding the effectiveness of DLPFC-targeting rTMS in alleviating the pain experienced by PLP patients.

OBJECTIVE: In this study, our aim was to investigate the impact of 10 sessions of DLPFC-targeting rTMS on the pain status of individuals experiencing PLP.

STUDY DESIGN: Randomized controlled trial.

SETTING: Traumatic amputees reporting to the tertiary care center with PLP.

METHODS: The study was approved by the Institute Ethics Committee (IECPG-299/27.04.2022) and registered in the Clinical Trials Registry of India (CTRI/2022/07/043938). Nineteen patients suffering from PLP were recruited and randomized into real or sham rTMS groups. In the real rTMS group, patients received 10 sessions of rTMS at the DLPFC contralateral to the amputation site. The rTMS, administered at 90% of the resting motor threshold (RMT), was delivered as 8 trains of 150 pulses per train at the rate of one Hz and an inter-train interval of 60 seconds. The total number of pulses per session was 1,200. The sham group received 10 sessions of sham rTMS through the perpendicular placement of an rTMS coil over the DLPFC. These sessions lasted for the same duration and included the same sounds as the real group but involved no active stimulation. The patients’ pain status was evaluated using the Visual Analog Scale (VAS) at baseline, at the end of each session of real or sham rTMS and at the 15th, 30th, and 60th day after the the completion of real or sham therapy.

RESULTS: A significant decrease in VAS scores was noted after 10 sessions of real rTMS that targeted the DLPFC, in contrast to the sham rTMS group. The real rTMS group’s reduction in VAS scores also persisted during the follow-up.

LIMITATIONS: A few patients had to drop out due to physical restrictions and financial constraints. Consequently, only a small number of individuals were able to complete the study protocol successfully.

CONCLUSION: A regimen of 10 sessions of real rTMS of the DLPFC was associated with significant pain relief in patients with PLP, and the effects were sustained for 2 months. Therefore, the present study shows that rTMS of the DLPFC has potential as an effective therapeutic intervention for sustained pain relief in PLP patients.  

KEY WORDS: Cortical reorganisation, cortical plasticity, DLPFC, neuropathic pain, noninvasive brain stimulation, neuromodulation, phantom limb pain, rTMS