The biology of virally initiated pain states

Virally initiated pain states occur across a wide range of species and viral families, but the mechanisms by which viral infection produces acute or chronic pain remain incompletely understood. This perspective is based on the presentation, “The Puzzle of Virally Induced and Sustained Pain States”, delivered at the 2025 International Veterinary Emergency and Critical Care Symposium (IVECCS) held in San Diego, California, September 4–8, 2025. Drawing on representative viral models, this perspective organizes mechanisms of virally initiated pain into three overlapping routes: direct neuronal infection or receptor activation, indirect modulation through non-neuronal and immune cells within infected tissue, and systemic immune signaling originating outside of the nervous system. By highlighting shared and distinct mechanisms across viral models, this comparative framework aims to guide mechanistic investigation and identify potential therapeutic targets for virally initiated pain across human and veterinary medicine.