It is unknown if different etiologies or lesions topography influence central neuropathic pain (CNP) clinical manifestation. We explored the symptom-somatosensory profile relationships in CNP patients with different types of lesions to the CNS to gain insight into CNP mechanisms. We compared CNP profile through pain descriptors, standardized bedside examination, and quantitative sensory test in two different etiologies with segregated lesion locations: the brain ̶ central post-stroke pain (CPSP, n=39) and the spinal cord ̶ central pain due to spinal cord injury in neuromyelitis optica ( CPSCI, n=40). CPSP presented higher evoked and paroxysmal pain scores compared to CPSCI, p< 0.001, and lower cold thermal limen (5.6°C (0.0-12.9)) compared to CPSCI (20.0°C (4.2-22.9); p =0.004). CPSCI also had higher mechanical pain thresholds 784.5mN (255.0-1078.0) compared to CPSP 235.2 mN (81.4-1078.0), p=0.006 and higher mechanical detection threshold compared to control areas 2.7 (1.5-6.2) vs. 1.0 (1.0-3.3), p=0.007. Evoked pain scores negatively correlated with mechanical pain thresholds (r=-0.38, p<0.001) and wind-up ratio (r=-0.57; P<0.001). CNP of different etiologies may present different pain descriptors and somatosensory profiles, which is likely due to injury site differences within the neuroaxis. This information may help better design phenotype-mechanism correlations and impact trial design for the main etiologies of CNP: stroke and spinal cord lesion. Perspective: This study evidenced that topography may influence pain symptoms and sensory profile. The findings suggest that central neuropathic pain mechanisms might vary according to pain etiology or lesion topography, impacting future mechanisms-based treatment choices.