Mechanisms of Pain and Itch Caused by Herpes Zoster (Shingles)

Study of humans with shingles or postherpetic neuralgia (PHN) is providing insights into pain mechanisms. Shingles pain is a combination of normal and neuropathic pain that reflects acute tissue and neural injury. PHN pain, which lasts after tissues have healed, is caused by persistent neural injuries. Spontaneous C-nociceptor activity has been documented in painful polyneuropathies and probably occurs in shingles as well, although there are no microneurographic studies of either shingles or PHN. It is uncertain if this persists in PHN since pathological examination of PHN-affected nerves and ganglia show chronic neuronal loss and quiescent scarring without inflammation. Skin-biopsy study has correlated the presence of PHN with the severity of persistent distal nociceptive axon loss, and autopsy has correlated pain persistence with segmental atrophy of the spinal cord dorsal horn, highlighting the importance of central responses to nerve injury. Pathological studies of tissues from patients with trigeminal neuralgia suggest that brief lancinating pains reflect ephaptic neurotransmission between adjacent denuded axons. The mechanisms of chronic spontaneous pain and mechanical allodynia remain uncertain despite considerable indirect evidence from animal models. Postherpetic itch is presumably caused by unprovoked firing of the peripheral and/or central neurons that mediate itch. If it occurs in neurons innervating skin left severely deafferented from shingles (“numb”), patients can give themselves painless injuries from scratching. Further human study, by electrophysiological recording, by structural and functional imaging, and by autopsy, should continue to provide much-needed insights.PerspectiveMany patients continue to have chronic pain and/or itch after shingles that is unrelieved by current treatments. Many will gladly volunteer for clinical studies, including autopsy, to try and improve understanding of these common and disabling conditions. Their prevalence makes highly powered studies feasible. Funding and organization are the current bottlenecks.