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Rethinking the causes of pain in herpes zoster and postherpetic neuralgia

the ectopic pacemaker hypothesis

Devor, Marshall

doi: 10.1097/PR9.0000000000000702
Review: PDF Only

Introduction: Pain in herpes zoster (HZ) and postherpetic neuralgia (PHN) is traditionally explained in terms of 2 processes: irritable nociceptors in the rash-inflamed skin and, later, deafferentation due to destruction of sensory neurons in one virally infected dorsal root ganglion.

Objectives and methods: Consideration of the evidence supporting this explanation in light of contemporary understanding of the pain system finds it wanting. An alternative hypothesis is proposed as a replacement.

Results: This model, the ectopic pacemaker hypothesis of HZ and PHN, proposes that pain in both conditions is driven by hyperexcitable ectopic pacemaker sites at various locations in primary sensory neurons affected by the causative varicella zoster virus infection. This peripheral input is exacerbated by central sensitization induced and maintained by the ectopic activity.

Conclusions: The shift in perspective regarding the pain mechanism in HZ/PHN has specific implications for clinical management.

This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0 (CC BY-ND) which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author.

Department of Cell and Developmental Biology, Institute of Life Sciences, and Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem, Israel

Corresponding author. Address: Department of Cell and Developmental Biology, Institute of Life Sciences 3-533, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Tel.: +972 2 658-5085; fax: +972 2 658-4480. E-mail address: (M. Devor).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received June 07, 2018

Accepted October 10, 2018

© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.