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

Authors

Ichiro Takasaki, Arata Inoue, Aoi Yoshida, Yuya Ashihara, Hiroyuki Mori

Published in

Pharmacological reports : PR. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition that develops following herpes zoster, yet the molecular mechanisms underlying the transition from acute herpetic pain to chronic 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. Therefore, this study investigated the temporal involvement of BDNF-TrkB signaling in acute herpetic pain and in the development of PHN-like pain.
A herpes simplex virus type-1 (HSV-1)-induced mouse model of herpetic pain was used to evaluate temporal changes in neurotrophin and Trk receptor expression in the dorsal root ganglia (DRG) and spinal dorsal horn. Pharmacological interventions included intrathecal administration of anti-BDNF, anti-Trk receptor antibodies or TrkB-Fc chimera, and repeated systemic treatment with the TrkB antagonist ANA-12 during the acute phase. Mechanical allodynia was behaviorally assessed.
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 in DRG. No neurotrophin or Trk receptor changes were observed in established PHN-like pain. Intrathecal administration of anti-BDNF antibody, anti-TrkB antibody, or TrkB-Fc chimera significantly attenuated acute mechanical allodynia, whereas anti-TrkA and anti-TrkC antibodies showed no significant effects. None of these interventions affected established PHN-like pain. Repeated administration of the TrkB antagonist ANA-12 during the acute phase attenuated acute herpetic pain and significantly reduced the subsequent incidence of PHN-like pain.
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.

PMID:
42455233
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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