Efficacy and Safety of Transcranial Temporal Interference Stimulation (tTIS) for Neuropathic Pain in Neuromyelitis Optica Spectrum Disorder (NMOSD)

Neuromyelitis optica spectrum disorder (NMOSD) is a rare but severe demyelinating condition that affects mainly adult patients. In the course of NMOSD, pain is a common accompanying symptom, aside from other symptoms such as visual impairment, limb weakness, limb numbness, and urinary and fecal dysfunction. Among these, neuropathic pain is the most common, affecting over 80% of patients with NMOSD. It occurs not only during the acute phase of NMOSD but also serves as the main form of chronic pain. Currently, there is no standard clinical protocol for the treatment of neuropathic pain, and the efficacy of analgesic drugs is limited. Transcranial temporal interference stimulation (tTIS) is emerging as a non-invasive therapeutic alternative to deep brain stimulation (DBS). Studies have shown that tTIS exerts a positive impact on neural function, including enhancing memory function and improving motor function. While it still remains underdeveloped about tTIS in the field of pain management. Based on this, we intend to conduct a small-sample prospective self-controlled study. By analyzing the baseline clinical characteristics, we will compare the changes in pain scale scores (Numerical Rating Scale [NRS], Visual Analog Scale [VAS]), Global Impression Scales, Short-Form McGill Pain Questionnaire, Painful Spasm Frequency Scale, and Hamilton Anxiety/Depression Scale scores before and after tTIS treatment. Through this, we aim to evaluate the efficacy and safety of this therapeutic approach in subjects suffered from NMOSD-related neuropathic pain.

Inclusion criteria

• Patients diagnosed with NMOSD in accordance with the criteria of the International Panel for Neuromyelitis Optica Diagnosis (IPND).
• Patients were complicated with neuropathic pain, with a DN4 score ≥ 4.
• NRS score for pain ≥ 4 points, and neuropathic pain has persisted for more than 3 months.
• Patients receiving biological therapy and/or prednisone at a stable dose, with no adjustment of the treatment plan within 30 days before enrollment.
• Patients who have not adjusted any combination of standard analgesic drugs (including antiepileptic drugs, antidepressants, and opioid drugs) within 30 days before enrollment.
• Patients or their family members who have signed a written informed consent form.

Exclusion criteria

• Subjects participating in other clinical studies.
• Subjects who have used investigational drugs for pain control within 30 days before enrollment.
• Subjects with a concurrent diagnosis of peripheral neuropathy.
• Subjects with concurrent active central nervous system diseases.
• Subjects with cognitive or mental disorders.
• Subjects who are pregnant, lactating, or planning to become pregnant during the study period.
• Subjects with severe diseases related to the heart, liver, kidneys, or hematopoietic system.
• Subjects with implanted devices in the body (such as cardiac pacemakers, nerve stimulators, etc.).
• Subjects with a history of transcutaneous electrical nerve stimulation (TENS) allergy, latex allergy, or previous intolerance.
• Subjects with contraindications to MRI examination.
• Subjects with head skin lesions.
• Other medical conditions or situations that the researcher deems may affect the achievement of the study objectives.