Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage

Shingles can cause chronic neuropathic pain (postherpetic neuralgia) long after skin lesions heal. To investigate its causes, we quantitated immunolabeled sensory neurites in skin biopsies from 18 subjects with and 16 subjects without postherpetic neuralgia after unilateral shingles. Subjects rated the intensity of their pain. Punch skin biopsies were evaluated from the site of maximum pain or shingles involvement, the homologous contralateral location, and a site on the back, distant from shingles involvement. Sections were immunostained with anti-PGP9.5 antibody, a pan- axonal marker, and the density of epidermal and dermal neurites determined. The group with postherpetic neuralgia had a mean density of 339 ± 97 neurites/mm² in shingles-affected epidermis compared with a density of 1,661 ± 262 neurites/mm² for subjects without pain. Neurite loss was more severe in epidermis than dermis. Unexpectedly, the group with pain had also lost half of the neurites in contralateral epidermis. Contralateral damage occurred despite the lack of contralateral shingles eruptions or pain, correlated with the presence and severity of ongoing pain at the shingles site, and did not extend to the distant site. Thus, the pathophysiology of postherpetic neuralgia pain may involve a new bilateral mechanism.