Background: Several pathophysiological mechanisms may be responsible for initiation and maintenance of chronic postherpetic pain. (1) Peripheral nociceptive fibers can develop abnormal sensitization. Secondary to this, central nociceptive "second-order" neurons in the spinal cord dorsal horn can also be sensitized, i.e. they become hyperexcitable and start responding to non-noxious stimuli. (2) Degeneration of nociceptive neurons may trigger anatomical sprouting of low-threshold mechanosensitive terminals to form connections with central nociceptive neurons and may subsequently induce functional synaptic reorganization in the dorsal horn. According to these mechanisms theoretical possibilities of therapeutical interventions to prevent postherpetic neuralgia are (1) adequate analgesia in the acute phase (analgesics, antidepressants, sympathetic blocks) and (2) prevention of C-fiber degeneration by reducing the inflammatory reaction (antiviral drugs, corticosteroids, neurotrophins).

Methods: The present clinical trials concerning prevention of postherpetic neuralgia were analyzed. Only for the antiviral drugs have valid clinical studies been performed. Using acyclovir a considerable reduction of acute pain and time to healing could clearly be demonstrated. However, there was no significant effect on prevention of postherpetic neuralgia. The second-generation antiviral drugs valaciclovir and famciclovir may be more effective when applied early in the disease course. Preliminary studies indicate that the early onset of therapy with the antidepressant agent amitriptyline may reduce the incidence of postherpetic neuralgia. These results need to be confirmed in further studies.

Conclusions: Although there is no clear evidence in favor of a prevention of postherpetic neuralgia for any of the interventions, it is definitely reasonable to perform the best analgesia possible during the acute phase of herpes zoster.