Immunoinflammatory mechanisms and emerging therapies for postherpetic neuralgia

This review examines the immunoinflammatory mechanisms underlying postherpetic neuralgia (PHN) and emerging mechanism-based therapies. PHN is increasingly recognized as a neuroimmune disorder driven by varicella-zoster virus reactivation, peripheral nerve injury, cytokine-mediated inflammation, oxidative stress, glial activation, and central sensitization. Although conventional treatments, including antidepressants, anticonvulsants, topical agents, opioids, and neuromodulation, provide symptomatic relief, they rarely modify the underlying disease process. A key scientific gap is the lack of consensus on the optimal timing, patient selection, and targets for immunomodulatory, gene-based, or RNA-based interventions to prevent the transition from acute neuroinflammation to chronic pain. Therefore, this review briefly summarizes standard-of-care therapies and focuses on emerging strategies targeting upstream mechanisms, including cytokine modulation, NLRP3 inflammasome inhibition, oxidative stress regulation, viral vector-based gene therapy, RNA interference, non-coding RNA approaches, and phenotype-guided precision medicine. We propose a stage-specific, mechanism-oriented framework for future PHN management.