The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. (Massachusetts General Hospital, Harvard Medical School, Boston, MA) Pain. 2001;92:139–145.

Postherpetic neuralgia (PHN), which occurs in some patients after shingles, was used to investigate the neural determinants of chronic pain. Skin biopsies were obtained from 38 adults with or without PHN at least 3 months after healing of shingles on the torso. Vertical sections were immunolabeled against PGP9.5, a pan‐axonal marker, to measure the density of the remaining nerve endings in skin previously affected by shingles. Of 19 subjects without PHN, 17 had more than 670 neurites/mm2 skin surface area, and 18 of 19 subjects with PHN had 640 or fewer neurites/mm2. PHN may be a “phantom‐skin” pain associated with loss of nociceptors. The study implies that the absence of pain after shingles may require the preservation of a minimum density of primary nociceptive neurons, and that the density of epidermal innervation may provide an objective correlate for the presence or absence of PHN pain. Comment by Miles Day, M.D. This is a good article addressing one of the most difficult chronic pain syndromes to treat. As you know postherpetic neuralgia can be devastating to the patients secondary to the ongoing and sometimes incapacitating pain. This study does not attempt to explain the cause of postherpetic neuralgia. Instead it establishes objective criteria that implies the absence of pain after shingles may require preservation of a minimum density of primary nociceptor neurons and that this density may provide an objective correlate for the presence or absence of postherpetic neuralgia pain. If the implication made by the study is true, it raises a question as to whether or not skin biopsy should be preformed on all patients who have just experienced a case of herpes zoster to determine whether or not they are at risk for developing postherpetic neuralgia. Another question that may arise is whether or not we should empirically treat certain patients for potential postherpetic neuralgia if there neurite density falls below a certain established level. While the information from this study should not be used as a sole factor in determining whether or not a patient with a previous herpes zoster infection will develop postherpetic neuralgia it does add objective data to our armamentarium that can be used to try to prevent or treat the devastating pain caused by postherpetic neuralgia.