Role of Supraspinal Neuroinflammation in Chronic Pain After Experimental Spinal Cord Injury—A Systematic Review

Spinal cord injury (SCI) is a major cause of long-term disability and is frequently accompanied by chronic pain, substantially reducing quality of life. Although spinal neuroinflammation is a recognized contributor to neuropathic pain, the role of supraspinal neuroinflammation remains less well defined. This systematic review critically evaluated experimental evidence linking SCI-induced supraspinal neuroinflammation with pain-related behaviors in animal models. A systematic literature search in PubMed, Web of Science Core Collection, and Scopus identified studies published over the last 20 years using rodent SCI models that assessed both supraspinal neuroinflammatory markers and pain-related behaviors. After screening, nine studies met the predefined criteria. The analyzed studies suggested that SCI is associated with supraspinal neuroinflammatory alterations, including increased microglial and astrocytic activation and upregulation of pro-inflammatory cytokines and chemokine-related pathways, in several brain regions. In intervention studies, reduced neuroinflammation was accompanied by improvement in mechanical or thermal pain-related behaviors. However, considerable methodological heterogeneity and moderate to high risk of bias were observed. Current evidence suggests an association between supraspinal neuroinflammatory alterations and chronic pain-related behaviors after SCI, but the limited number of studies and methodological variability restrict firm conclusions. Further well-designed experimental studies are needed to clarify underlying mechanisms.