Effects of Prolonged Continuous Theta Burst Stimulation in Chemotherapy-induced Peripheral Neuropathy

Effects of Prolonged Continuous Theta Burst Stimulation in Chemotherapy-induced Peripheral Neuropathy: a Randomized Cross- Over Trial

Laboratory studies have shown that prolonged continuous theta burst stimulation (pcTBS) provides better pain relief than 10 Hz repetitive transcranial magnetic stimulation (rTMS), with a shorter stimulation time, making it more practical for clinical use. Chemotherapy-induced peripheral neuropathy often causes neuropathic pain in cancer patients. The aims of this study are:

1. To compare the effects of pcTBS and 20 Hz rTMS on chemotherapy-induced peripheral neuropathy;
2. To compare the effects of pcTBS applied to the primary motor cortex versus the dorsolateral prefrontal cortex on neuropathic pain as well as depression and anxiety.

**Phase 1:** Investigators will recruit 20 breast cancer patients who have chemotherapy-induced peripheral neuropathy. They will be randomly divided into two groups.

• Group 1 will first receive pcTBS. After an 8-week break, they will then receive 20 Hz rTMS.
• Group 2 will receive the treatments in the opposite order.

Each treatment lasts for 5 consecutive days. Before and after each treatment, patients will be assessed using:

• A pain visual analog scale (to measure pain levels)

• A Neuropathic Pain Symptom Inventory (The scale ranges from zero to 10, with zero indicating no pain at all and 10 indicating the worst imaginable pain)

  • * A Depression Anxiety Stress Scale 21 (The scale ranges from 0-63, with a higher scores mean a worse outcome)

  o * Clinical pressure pain threshold tests (Higher PPT values indicate a higher tolerance to pressure pain (less sensitivity).

• Nerve conduction studies **Phase 2:** Another 20 breast cancer patients with chemotherapy-induced peripheral neuropathy will be recruited and randomly divided into two groups.

• Group 1 will first receive pcTBS on the primary motor cortex. After an 8-week break, they will receive the same stimulation on the left dorsolateral prefrontal cortex.

• Group 2 will receive the treatments in the opposite order.

Inclusion Criteria:

• breast cancer patients aged between 18- and 80-years-old with CIPN
• history of receiving chemotherapy including taxane-based neurotoxic agents
• with neuropathic pain, score≥3 in a 0-10 VAS pain scale.
• with fair cognition and can cooperate to evaluate pain severity.
• neither at end-stage cancer nor at the estimated survival time less than 6 months.

Exclusion Criteria:

• brain tumor or history of epilepsy
• intracranial metallic devices, artificial cochleae, pacemakers, or any other metal device
• recent myocardial ischemia or unstable angina
• severe cognitive dysfunction or pregnancy
• injuries or fractures in the part of neuropathic pain