OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) causes disabling and persistent central neuropathic pain (NP). Because the pain syndrome in NMOSD is severe and often intractable to analgesic treatment, it interferes with quality of life in patients. No interventional trials have been published looking at response to interventions for pain in NMOSD. This is a synthesis of the literature surveying the impact on quality of life of interventions in all mechanisms of central spinal NP. This review has important implications for management of pain in NMOSD. METHODS AND DATA SOURCES: A systematic database search was conducted using PubMed, Embase, and CINAHL Plus with keywords including spinal cord, quality of life, and neuropathic pain in an attempt to identify original research that targeted spinal NP treatment and used quality of life as an outcome measure. Both pharmacologic and nonpharmacologic treatments were sought out. RESULTS: Twenty-one studies meeting our eligibility criteria were identified and evaluated, 13 using pharmacologic treatments and 8 using nonpharmacologic interventions. Overall, sample sizes were modest, and effects on decreasing pain and/or improving quality of life were suboptimal. CONCLUSIONS: This review provides researchers with a foundation from which to start a more thorough and thoughtful investigation into the management of NP in NMOSD and underscores the importance of including quality of life as a clinically meaningful outcome measure.