Identification of a reactive astrocyte subpopulation during HIV-associated pain pathogenesis in mouse models

Pain is a common complication in individuals with HIV, yet the underlying pathogenic mechanisms remain poorly understood. Reactive astrocytes are selectively activated in the spinal dorsal horn of HIV patients experiencing pathological pain, implicating their potential role in pain pathogenesis. However, the specific pathogenic subtype of these reactive astrocytes has not been defined. Here, we identify a distinct subpopulation of pain-associated reactive astrocytes in the lumbar spinal cord of HIV-1 gp120 transgenic mice using single-nucleus RNA sequencing. This astrocyte subpopulation displays transcriptomic features associated with phagocytosis and inflammation and depends on galectin-3 for its formation. Both global and astrocyte-specific heterozygous knockout of Lgals3 (galectin-3) markedly reduce mechanical allodynia in gp120 transgenic mice. These findings reveal a subset of reactive astrocytes that play a role in remodeling the spinal pain circuitry underlying HIV-associated pain.