BackgroundPost-herpetic neuralgia (PHN), which develops after the resolution of a herpes zoster eruption, is an exceptionally drug-resistant neuropathic pain. The unsatisfactory management of PHN partly results from the difficulty in dissecting out its contributing factors due to the complexity of PHN mechanism. 

MethodsHere, to elaborate our understanding of the PHN mechanism and to establish a basis for effective therapeutic strategies, we comprehensively investigated the contributions of multiple factors to PHN severity. 

ResultsBased on the comparison of somatosensory detection thresholds (C, A and A fibre thresholds) between affected and unaffected sides, 16 PHN patients with significant sensory deficits and 13 PHN patients without significant sensory deficits were identified and assigned to different groups. The different extents of lesions in the nociceptive system between patients with and without sensory deficits were confirmed using laser-evoked brain responses. Moreover, patients with sensory deficits had more severe pain and psychological disorders, e.g. anxiety and depression. Importantly, chronic pain severity was significantly influenced by various psychophysiological factors (sleep disturbances, psychological disorders and hypothalamic-pituitary-adrenal axis dysfunction) for patients with sensory deficits. 

ConclusionsOur findings demonstrated the contribution of multiple patho-psychophysiological factors to PHN severity, which could help establish a basis for the development of a rational, patient-centred therapeutic strategy. 

SignificanceThis study revealed the contribution of multiple patho-psychophysiological factors to PHN severity, which expanded our understanding of the underlying PHN mechanism, and helped develop a rational, patient-centred therapeutic strategy targeting towards the corresponding etiology and psychophysiological disorders for individual patient.