Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models.
Pain and post-herpetic neuralgia (PHN) are common and highly distressing complications of herpes zoster that remain a significant public health concern and in need of improved therapies. Zoster results from reactivation of the herpesvirus varicella zoster virus (VZV) from a neuronal latent state established at the primary infection (varicella). PHN occurs in some one fifth to one third of zoster cases with severity, incidence, and duration of pain increasing with rising patient age. While VZV reactivation and the ensuing ganglionic damage trigger the pain response, the mechanisms underlying protracted PHN are not understood, and the lack of an animal model of herpes zoster (reactivation) makes this issue more challenging. A recent preclinical rodent model has developed that opens up the potential to allow the exploration of the underlying mechanisms and treatments for VZV-induced pain. Rats inoculated with live cell-associated human VZV into the hind paw reliably demonstrate thermal hyperalgesia and mechanical allodynia for extended periods and then spontaneously recover. Dorsal root ganglia express a limited VZV gene subset, including the IE62 regulatory protein, and upregulate expression of markers suggesting a neuropathic pain state. The model has been used to investigate treatment modalities and aspects of pain signaling and is under investigation by the authors to delineate VZV genetics involved in the induction of pain. This article compares human zoster-associated pain and PHN to the pain indicators in the rat and poses important questions that, if answered, could be the basis for new treatments.
Department of Ophthalmology, University of Pittsburgh, 1020 EEI Building, 203 Lothrop Street, Pittsburgh, PA 15213, USA. kinchingtonp@upmc.edu
Paul R
PR
Kinchington
William F
WF
Goins
D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000821:virology; D017930:Genes, Reporter; D006566:Herpesviridae Infections / Q000150:complications / Q000503:physiopathology* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology / Q000821:virology; D051379:Mice; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology* / Q000821:virology; D051474:Neuralgia, Postherpetic / Q000209:etiology / Q000503:physiopathology* / Q000821:virology; D051381:Rats; D011984:Sensory Receptor Cells / Q000166:cytology / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014775:Virus Activation / Q000502:physiology; D017735:Virus Latency / Q000502:physiology
D014759:Viral Envelope Proteins