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.

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).

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