Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Nov 7;3(6):e702.
doi: 10.1097/PR9.0000000000000702. eCollection 2018 Nov.

Rethinking the causes of pain in herpes zoster and postherpetic neuralgia: the ectopic pacemaker hypothesis

Marshall Devor  1
Affiliations
Review

Rethinking the causes of pain in herpes zoster and postherpetic neuralgia: the ectopic pacemaker hypothesis

Marshall Devor. Pain Rep. .

Abstract

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.

Keywords: Deafferentation; Dorsal root ganglion; Dying-back; Ectopic discharge; Herpes zoster; Pain mechanism; Postherpetic neuralgia.

PubMed Disclaimer

Conflict of interest statement

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

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Andrew D, Greenspan JD. Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat. J Neurophysiol 1999;82:2649–56. - PubMed
    1. Banik RK, Brennan TJ. Spontaneous discharge and increased heat sensitivity of rat C-fiber nociceptors are present in vitro after plantar incision. PAIN 2004;112:204–13. - PubMed
    1. Banik RK, Brennan TJ. Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation. PAIN 2008;138:380–91. - PMC - PubMed
    1. Baron R, Saguer M. Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 1993;116(pt 6):1477–96. - PubMed
    1. Bove GM, Ransil BJ, Lin HC, Leem JG. Inflammation induces ectopic mechanical sensitivity in axons of nociceptors innervating deep tissues. J Neurophysiol 2003;90:1949–55. - PubMed

LinkOut - more resources