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Background: Central Post Stroke Pain (CPSP) is reportedly due to strokes in the thalamic region (Dishinbition Theory); however, the Central Imbalance Theory states that CPSP is due to damage to the spinothalamic pathway (STP).Aims: 1) Clarify the role of thalamic strokes and STP damage in CPSP patients. 2) Gain a current understanding of anatomic substrates, brain imaging, and treatment of CPSP.Methods: Two independent reviewers systematically reviewed PUBMED, CINAHL and Web of Science for studies including original, clinical studies and randomized controlled trials (RCTs) using PRISMA guidelines. Studies had to assess CPSP, using a single question or pain scale.Results: Search from January – July 2016, identifying 731 publications. We extracted data from 23 studies and categorized the articles’ aims into 4 sections: somatosensory deficits (5 studies), STP (3 studies), brain imaging (7 studies), and RCTs (8 studies). Somatosensory studies showed high rates of CPSP; however, the underlying causes of these deficits were unclear. Most studies did not refer to stroke location as playing a role in CPSP, but that pathways may. STP studies displayed consistent evidence that the STP plays a major role in CPSP, delineating that CPSP can occur even when the stroke is not in the thalamic region but in other regions (e.g. cerebellum, basal ganglia, medulla). Four of the brain imaging studies found CPSP not related and 3 found it was related to thalamic strokes. All 7 studies had major limitations including sample size, no control groups, and selection bias. RCTs were mostly negative, but brain stem and motor cortex stimulation studies showed the most promise.Conclusions: While CPSP has been linked to the thalamic region since the early 1900’s, the peer-reviewed literature showed equivocal results when examining location of stroke. Our systematic review suggests damage to the STP is associated with CPSP and this could provide insights into mechanisms and treatment. Moreover, historical connection of strokes in thethalamic region and CPSP should be reevaluated as many studies noted that strokes in other regions of the brain also produce CPSP.