Low-Level Light Therapy in Postherpetic Neuralgia: A Review of Mechanistic Insights and Clinical Implications.

Known as the most prevailing complication of herpes zoster (HZ), postherpetic neuralgia (PHN) can lead to long-term skin discomfort. Current medications for PHN remain suboptimal with incomplete relief and potential side effects. Low-level light therapy (LLLT) has been increasingly explored as a non-invasive modality for treating PHN, but the mechanistic basis and clinical implications have not been synthesized in a translational framework. In this review, we explore the pathophysiological mechanisms of PHN and the biological mechanisms of LLLT, integrating current mechanistic insights with available clinical evidence. We summarize the experimental and clinical literature evaluating LLLT for PHN and related neuropathic pain models, mainly focusing on mechanisms across peripheral tissues, dorsal root ganglia, and neuro-immune aspects, as we evaluate therapeutic parameters and outcomes from available clinical studies. Current evidence suggests that PHN is associated with dorsal root ganglion (DRG) inflammation, peripheral cutaneous neuroinflammation, loss of cutaneous innervation, and ion channel dysregulation. These changes comprehensively lead to hyperexcitable neurons with a lower sensory threshold. Across neuropathic pain models, LLLT elevates mechanical and thermal pain thresholds, attenuates inflammatory cytokine signaling, and promotes an immune cell phenotype shift toward an anti-inflammatory profile including M1-to-M2 macrophage polarization. LLLT also stabilizes membrane excitability by restoring Na⁺/K⁺-ATPase activity and modulating calcium dynamics, while supporting peripheral nerve repair via axonal regeneration. Clinically, administering LLLT to patients with PHN resulted in significant pain reduction, and early intervention may also reduce its incidence. By integrating experimental and clinical research, LLLT serves as a promising approach for PHN owing to its efficacy for anti-inflammation, neuronal regeneration and ion modulation.