Dorsal Root Ganglion-Mediated Modulation of Neuroinflammation and Neurovasodilation in Rosacea by Gabapentin

Neurogenic rosacea features disproportionate pain and erythema resistant to conventional treatments. While gabapentin shows clinical efficacy, its molecular mechanism remains undefined.Using a murine rosacea model induced by LL37, we performed bulk RNA sequencing and molecular analyses of skin and dorsal root ganglia (DRG) to assess gabapentin's effects. LL37 triggered parallel neuroimmune and neurovascular activation in skin and DRG, including upregulating of Th2, IGF, CGRP, and nitric oxide synthases. Gabapentin suppressed CGRP expression, NF-?B phosphorylation, and neurovascular remodeling, particularly in DRG and skin. Transcriptomic and protein analyses revealed that gabapentin modulates neuronal excitability and inflammatory signaling via GABAergic and calcium channel pathways. Gabapentin exerts anti-neuroinflammatory and anti-neurovascular actions via DRG-mediated pathways in rosacea. These findings identify the peripheral nervous system as a central therapeutic target and establish gabapentin's molecular rationale in treating neurogenic skin inflammation. Overall design: Female BALB/c mice (6 weeks old) were treated with intradermal LL37 (320 µM, 40 µL, twice daily for 2 days). Gabapentin (100 mg/kg in water, oral, twice daily) was administered from day 3. On day 4, dorsal root ganglion tissue was collected for RNA sequencing.