Peripheral nerve transection predominantly drives sympathetic nerve sprouting in mouse dorsal root ganglia

Abstract Sympathetic sprouting in dorsal root ganglia (DRG) is a feature of sympathetically maintained pain (SMP) after peripheral nerve injury, yet the factors determining its occurrence remain unclear. Here, we compare transection and crush injury models to determine whether injury type or site influence sympathetic remodeling and pain. Using tyrosine hydroxylase-immunoreactivity staining and Phox2b reporter mice to selectively label sympathetic fibers, we found that an L5 spinal nerve transection triggered robust sympathetic fiber sprouting and elevated norepinephrine (NE) levels in the DRG, correlating with mechanical hypersensitivity that was reversed by chemical sympathectomy. By contrast, a partial sciatic nerve crush injury produced long-lasting mechanical hypersensitivity without sympathetic sprouting or NE elevation and was unaffected by sympathectomy. Importantly, sympathetic sprouting was consistently more pronounced after transection injuries at both spinal and sciatic nerve sites, suggesting that injury type, rather than location, is a dominant factor shaping sympathetic remodeling. These findings establish nerve transection as a key driver of sympathetic sprouting and SMP, whereas crush-induced pain likely involves distinct nonsympathetic mechanisms. This distinction has important implications for pain subtype identification and treatment strategies.