Phase-specific involvement of BDNF–TrkB signaling in HSV-1– induced herpetic pain and its transition to postherpetic neuralgia-like pain

Background Postherpetic neuralgia (PHN) develops after acute herpes zoster, yet the molecular mechanisms driving the transition from acute herpetic pain to persistent neuropathic pain remain unclear. Brain-derived neurotrophic factor (BDNF)–TrkB signaling is implicated in central sensitization, but its role in virus-induced pain chronification is unknown. Methods Using a herpes simplex virus type-1 (HSV-1)–induced mouse model, we examined temporal changes in neurotrophin and Trk receptor expression in the dorsal root ganglia (DRG) and spinal dorsal horn. Pharmacological interventions included intrathecal administration of a BDNF-neutralizing antibody or TrkB-Fc chimera, selective Trk receptor blockade, and repeated systemic treatment with the TrkB antagonist ANA-12 during the acute phase. Mechanical allodynia was behaviorally assessed. Results BDNF mRNA expression was significantly upregulated in ipsilateral DRG and spinal dorsal horn during the acute phase, whereas neurotrophin-3 remained unchanged and nerve growth factor showed only transient increases. No neurotrophin or Trk receptor changes were observed in established PHN-like pain. BDNF neutralization or TrkB blockade attenuated acute mechanical allodynia but did not affect established pain. Selective TrkB inhibition alleviated acute herpetic pain, and repeated ANA-12 treatment reduced the incidence of PHN-like pain. Discussion BDNF–TrkB signaling plays a phase-specific role in herpetic pain, driving acute pain expression and the transition to chronic PHN-like pain but not pain maintenance. Early TrkB inhibition may represent a disease-modifying strategy to prevent viral pain chronification.