Abstract Background Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. Through the previous literature study and clinical observation, we found that acupuncture has good curative effect in the treatment of pain, especially electric acupuncture, but thestudies on acupuncture intervention in pain of NMOSD are still scare. Objective To evaluate the clinical efficacy of electroacupuncture on NMOSD patients with pain. Materials and Methods In this exploratory randomized controlled study, NMOSD patients with pain were recruited from March 21, 2022 to February 21, 2023. Patients meeting the inclusion and exclusion criteria were randomly assigned to the electroacupuncture group (experimental group) and the sham electroacupuncture group (control group) by simple random method (envelope method) according to the inclusion order. Totally, there are 20 patients enrolled. The experimental group received electroacupuncture therapy and the control group received sham electroacupuncture therapy. A total of 8 sessions were given twice a week for 30 minutes each. On the baseline, demographic information, medication history, specimens of routine blood, blood biochemistry, liver function, IL - 6, TNF-α were collected, the brain, cervical and thoracic MRI were perfected and collected, patients filled in the SF - MPQ, NRS, SF - 36, SAS, SDS, EDSS. After the treatment, specimens of routine blood, blood biochemistry, liver function, IL - 6, TNF-α were collected again, patients filled in the SF - MPQ, NRS, SF - 36, SAS, SD, EDSS. The main outcome indicators were SF-MPQ, and the secondary outcome indicators were EDSS, NRS, SAS, SDS, SF-36, IL-6, and TNF-α. Conclusion This is the first exploratory randomized controlled study to evaluate the efficacy of electroacupuncture on pain in patients with NMOSD. The study will provide clincial evidence of the practice of electroacupuncture on NMOSD with pain. Key Words neuromyelitis optica spectrum disorders; pain; electroacupuncture