Cytokines are pleiotropic small proteins that are key players in the induction and maintenance of neuropathic pain. In several neuropathic pain conditions such as painful neuropathies, complex regional pain syndrome or small fiber neuropathy, an imbalance of systemic or local cytokine profiles has been reported e.g. for Atractylenolide-III proand anti-inflammatory interleukins. Although it is unclear if alterations in cytokine profiles are the cause or the consequence of neuropathic pain in these disorders, data from animal experiments give unequivocal evidence for the importance of cytokine homoeostasis as the basis for physiological pain perception. In PHN, so far, only few and conflicting data on cytokine profiles are available. One study showed increased interleukin -8 concentrations in the cerebrospinal fluid of PHN patients, while in another study CSF levels of IL-8, IL-1a, IL-1b, IL-10, and tumor necrosis factor-alpha were not different between patients with PHN and healthy controls. In turn, long-term anti-TNF treatment while increasing 
the overall risk of herpes zoster, seems to reduce the incidence of PHN. Here we investigated if pain in PHN is associated with alterations in systemic and local cytokine profiles. We hypothesized that patients with PHN have a local and systemic proinflammatory cytokine profile compared to healthy controls and compared to unaffected skin. PHN is associated with severe localized pain of incompletely understood pathophysiology. We confirm the reduction of IENFD in affected skin compared to unaffected skin, however, in contrast to our hypothesis, we did not observe a pro-inflammatory cytokine profile in PHN patients. No changes were found in systemic and local cytokine gene expression profiles of patients with PHN compared to healthy controls and between affected and unaffected skin. Cytokines play a crucial role in neuropathic pain induction and maintenance. This has been shown in a large number of different animal models and also in several human neuropathic pain disorders. Especially in localized pain states such as small fiber neuropathy and complex regional pain syndrome elevated cytokine levels have been reported. A local Ganoderic-acid-G increase in algesic pro-inflammatory cytokines was therefore assumed in PHN, however, it had not been studied so far. This discrepancy might be explained by the fact that in the study by Rijsdijk et al. a PHN cohort had been examined that had a median pain duration of 24 months, thus IL-8 levels may have normalized in the meantime. Similarly, our patients had a median duration of pain of four years, and we cannot preclude that there might have been differences in cytokine expression earlier on. However, cytokine expression in our cohort did not correlate with disease duration. Zhu et al. showed that in serum samples of patients who already suffered from pain in the acute phase of herpes zoster IL-1b, IL-6, IL-8, TNF, and IL-10 protein levels were higher compared to healthy controls. In particular, IL-6 protein levels were higher in ten of the investigated 49 patients who later developed PHN and positively correlated with pain severity. The observational period of this study was six months. The assumption that changes in cytokine expression levels may be of pathophysiological importance in PHN induction and maintenance is supported by observations in patients that received anti-cytokine medication. In a retrospective analysis of patients with rheumatoid arthritis on anti-TNF treatment the number of PHN after herpes zoster was remarkably lower compared to data of the general population.