The Pathology of Postherpetic Neuralgia and Postherpetic Itch

Abstract

Postherpetic neuralgia (PHN) is one of the most studied neuropathic pain conditions because it is common, it is easy to diagnose, and the causal injury (zoster) can be precisely localized anatomically and temporally. Head and Campbell’s 1900 masterpiece mapping the locations of shingles rashes in almost 500 patients and then correlating this with autopsy localization of affected ganglia was how the sensory dermatomes were mapped. It also defined the pathology of zoster-affected spinal cord, nerve root, sensory ganglion, and peripheral nerves. Later studies focused on identifying pathological substrates for PHN. Watson’s group discovered that typical single-ganglion zoster damages up to five segments of the dorsal horn of the spinal cord, helping to explain why the PHN pain is felt in more than the one dermatome affected by the shingles rash. Oaklander’s team reported that PHN arises almost exclusively in patients with fewer than 650 epidermal nerve fibers/mm2 left after zoster, suggesting that PHN involves somatosensory hallucinations generated by deafferented central neurons. They also discovered that clinically unilateral zoster triggers bilateral pathology and that postherpetic itch and associated painless self-injury arise in skin lacking almost all C-fiber innervation, when isolated remaining itch neurons fire spontaneously and can no longer trigger surround inhibition in the dorsal horn. Hamrah’s group applied in vivo corneal confocal microscopy to confirm the presence of bilateral nerve degeneration after clinically unilateral herpes zoster ophthalmicus. Pathological study of patients with acute zoster and its neuropathic sequelae helped to identify normal somatosensory anatomy as well as the mechanisms of neuropathic pain and itch.