Background <p>Postherpetic neuralgia (PHN) is a typical neuropathic pain syndrome and frequently involves central and peripheral neuropathic signs. Considering the long-term pain conditions, pain, sleep disturbance, and mental disorders often create a self-perpetuating vicious cycle, wherein each factor exacerbates the others. The current understanding of the complex pathology of PHN remains limited, which hinders the clinical treatment of its pain symptoms.</p> Methods <p>To explore the neurobiological alterations linked with PHN, we utilized a novel method, the neuroimaging epicenter, to identify the candidate sites of its pathological processes and further investigated the related neurobiological signatures by exploring the associations of gene expression, neurotransmitter receptors/transporters distribution, and functional activity.</p> Results <p>As the primary epicenter, the ventroanterior thalamus is suggested to be the candidate region involved in the onset of the PHN neuropathophysiology. Furthermore, neuroimaging epicenters are related with clinical symptoms including pain, sleep disturbance, and anxiety and depression levels. And neuroimaging epicenters are correlated with downstream pain activity, upstream neurotransmitter receptors/transporters distribution mainly including opioid and acetylcholine, and gene expression maps.</p> Conclusions <p>we used a novel method to identify the ventroanterior thalamus as the potential epicenter of PHN, supported by the neurobiological interpretations. The presence of epicenters highlights that there may exist a reliable neuroimaging biomarker, which offers potential treatment targets.</p>