Journal of NeuroVirology

, Volume 17, Issue 6, pp 590–599 | Cite as

Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models

  • Paul R. Kinchington
  • William F. Goins


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.


Varicella zoster virus Human herpesvirus 3 Post-herpetic neuralgia Pain measurement Animal models Allodynia Hyperalgesia 



The authors wish to acknowledge funding and support for this work by NIH grant NS064022 from the National Institute of Neurological Diseases and Stroke, by core grant EY08098 from the National Eye Institute, and by unrestricted funds from the Eye & Ear Institute of Pittsburgh and from Research to Prevent Blindness, Inc. We also thank Mike Yee and Mingdi Zhang for excellent technical assistance.


  1. Ambagala AP, Cohen JI (2007) Varicella-zoster virus IE63, a major viral latency protein, is required to inhibit the alpha interferon-induced antiviral response. J Virol 81:7844–7851. doi: 10.1128/JVI.00325-07 PubMedCrossRefGoogle Scholar
  2. Ambagala AP, Bosma T, Ali MA, Poustovoitov M, Chen JJ, Gershon MD, Adams PD, Cohen JI (2009) Varicella-zoster virus immediate-early 63 protein interacts with human antisilencing function 1 protein and alters its ability to bind histones h3.1 and h3.3. J Virol 83:200–209. doi: 10.1128/JVI.00645-08 PubMedCrossRefGoogle Scholar
  3. Annunziato P, LaRussa P, Lee P, Steinberg S, Lungu O, Gershon AA, Silverstein S (1998) Evidence of latent varicella-zoster virus in rat dorsal root ganglia. J Infect Dis 178(Suppl 1):S48–S51PubMedCrossRefGoogle Scholar
  4. Argoff CE (2011) Review of current guidelines on the care of postherpetic neuralgia. Postgrad Med 123:134–142. doi: 10.3810/pgm.2011.09.2469 PubMedCrossRefGoogle Scholar
  5. Arvin AM, Moffat JF, Sommer M, Oliver S, Che X, Vleck S, Zerboni L, Ku CC (2010) Varicella-zoster virus T cell tropism and the pathogenesis of skin infection. Curr Top Microbiol Immunol 342:189–209. doi: 10.1007/82_2010_29 PubMedCrossRefGoogle Scholar
  6. Aunhachoke K, Bussaratid V, Chirachanakul P, Chua-Intra B, Dhitavat J, Jaisathaporn K, Kaewkungwal J, Kampirapap K, Khuhaprema T, Pairayayutakul K, Pitisuttithum P, Sindhvananda J, Thaipisuttikul Y (2011) Measuring herpes zoster, zoster-associated pain, post-herpetic neuralgia-associated loss of quality of life, and healthcare utilization and costs in Thailand. Int J Dermatol 50:428–435. doi: 10.1111/j.1365-4632.2010.04715.x PubMedCrossRefGoogle Scholar
  7. Azarkh Y, Dolken L, Nagel M, Gilden D, Cohrs RJ (2011) Synthesis and decay of varicella zoster virus transcripts. J Neurovirol 17:281–287. doi: 10.1007/s13365-011-0029-2 PubMedCrossRefGoogle Scholar
  8. Baron R, Saguer M (1993) Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 116(Pt 6):1477–1496PubMedCrossRefGoogle Scholar
  9. Baron R, Saguer M (1995) Mechanical allodynia in postherpetic neuralgia: evidence for central mechanisms depending on nociceptive C-fiber degeneration. Neurology 45:S63–S65PubMedGoogle Scholar
  10. Bennett GJ (1994) Hypotheses on the pathogenesis of herpes zoster-associated pain. Ann Neurol 35(Suppl):S38–S41PubMedCrossRefGoogle Scholar
  11. Bowsher D (1997) The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage 13:327–331PubMedCrossRefGoogle Scholar
  12. Chaves SS, Haber P, Walton K, Wise RP, Izurieta HS, Schmid DS, Seward JF (2008) Safety of varicella vaccine after licensure in the United States: experience from reports to the vaccine adverse event reporting system, 1995–2005. J Infect Dis 197(Suppl 2):S170–S177. doi: 10.1086/522161 PubMedCrossRefGoogle Scholar
  13. Chen N, Yang M, He L, Zhang D, Zhou M, Zhu C (2010) Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev:CD005582. doi: 10.1002/14651858.CD005582.pub3
  14. Christensen J, Steain M, Slobedman B, Abendroth A (2011) Differentiated neuroblastoma cells provide a highly efficient model for studies of productive varicella-zoster virus infection of neuronal cells. J Virol 85:8436–8442. doi: 10.1128/JVI.00515-11 PubMedCrossRefGoogle Scholar
  15. Cohen JI (2010) Rodent models of varicella-zoster virus neurotropism. Curr Top Microbiol Immunol 342:277–289. doi: 10.1007/82_2010_11 PubMedCrossRefGoogle Scholar
  16. Cohen JI, Cox E, Pesnicak L, Srinivas S, Krogmann T (2004) The varicella-zoster virus open reading frame 63 latency-associated protein is critical for establishment of latency. J Virol 78:11833–11840. doi: 10.1128/JVI.78.21.11833-11840.2004 PubMedCrossRefGoogle Scholar
  17. Cohrs RJ, Gilden DH, Kinchington PR, Grinfeld E, Kennedy PG (2003) Varicella-zoster virus gene 66 transcription and translation in latently infected human Ganglia. J Virol. 77(12):6660–6665. PubMed PMID: 12767985; PubMed Central PMCID: PMC156202Google Scholar
  18. Cohrs RJ, Gilden DH (2007) Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia. J Virol 81:2950–2956. doi: 10.1128/JVI.02745-06 PubMedCrossRefGoogle Scholar
  19. Dalziel RG, Bingham S, Sutton D, Grant D, Champion JM, Dennis SA, Quinn JP, Bountra C, Mark MA (2004) Allodynia in rats infected with varicella zoster virus—a small animal model for post-herpetic neuralgia. Brain Res Brain Res Rev 46:234–242. doi: 10.1016/j.brainresrev.2004.07.008 PubMedCrossRefGoogle Scholar
  20. Delaney A, Colvin LA, Fallon MT, Dalziel RG, Mitchell R, Fleetwood-Walker SM (2009) Postherpetic neuralgia: from preclinical models to the clinic. Neurotherapeutics 6:630–637. doi: 10.1016/j.nurt.2009.07.005 PubMedCrossRefGoogle Scholar
  21. Eisfeld AJ, Turse SE, Jackson SA, Lerner EC, Kinchington PR (2006) Phosphorylation of the varicella-zoster virus (VZV) major transcriptional regulatory protein IE62 by the VZV open reading frame 66 protein kinase. J Virol 80:1710–1723. doi: 10.1128/JVI.80.4.1710-1723.2006 PubMedCrossRefGoogle Scholar
  22. Eisfeld AJ, Yee MB, Erazo A, Abendroth A, Kinchington PR (2007) Downregulation of class I major histocompatibility complex surface expression by varicella-zoster virus involves open reading frame 66 protein kinase-dependent and -independent mechanisms. J Virol 81:9034–9049. doi: 10.1128/JVI.00711-07 PubMedCrossRefGoogle Scholar
  23. Esiri MM, Tomlinson AH (1972) Herpes zoster. Demonstration of virus in trigeminal nerve and ganglion by immunofluorescence and electron microscopy. J Neurol Sci 15:35–48PubMedCrossRefGoogle Scholar
  24. Fleetwood-Walker SM, Quinn JP, Wallace C, Blackburn-Munro G, Kelly BG, Fiskerstrand CE, Nash AA, Dalziel RG (1999) Behavioural changes in the rat following infection with varicella-zoster virus. J Gen Virol 80(Pt 9):2433–2436PubMedGoogle Scholar
  25. Freeman ML, Sheridan BS, Bonneau RH, Hendricks RL (2007) Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections. J Immunol 179:322–328PubMedGoogle Scholar
  26. Garry EM, Delaney A, Anderson HA, Sirinathsinghji EC, Clapp RH, Martin WJ, Kinchington PR, Krah DL, Abbadie C, Fleetwood-Walker SM (2005) Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs. Pain 118:97–111. doi: 10.1016/j.pain.2005.08.003 PubMedCrossRefGoogle Scholar
  27. Gershon AA, Gershon MD, Breuer J, Levin MJ, Oaklander AL, Griffiths PD (2010) Advances in the understanding of the pathogenesis and epidemiology of herpes zoster. J Clin Virol 48(Suppl 1):S2–S7. doi: 10.1016/S1386-6532(10)70002-0 PubMedCrossRefGoogle Scholar
  28. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA (2009) Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 8:731–740. doi: 10.1016/S1474-4422(09)70134-6 PubMedCrossRefGoogle Scholar
  29. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA (2010) Neurological disease produced by varicella zoster virus reactivation without rash. Curr Top Microbiol Immunol 342:243–253. doi: 10.1007/82_2009_3 PubMedCrossRefGoogle Scholar
  30. Gilden D, Mahalingam R, Nagel MA, Pugazhenthi S, Cohrs RJ (2011) Review: the neurobiology of varicella zoster virus infection. Neuropathol Appl Neurobiol 37:441–463. doi: 10.1111/j.1365-2990.2011.01167.x PubMedCrossRefGoogle Scholar
  31. Goss JR, Harley CF, Mata M, O’Malley ME, Goins WF, Hu X, Glorioso JC, Fink DJ (2002) Herpes vector-mediated expression of proenkephalin reduces bone cancer pain. Ann Neurol 52:662–665. doi: 10.1002/ana.10343 PubMedCrossRefGoogle Scholar
  32. Gowrishankar K, Slobedman B, Cunningham AL, Miranda-Saksena M, Boadle RA, Abendroth A (2007) Productive varicella-zoster virus infection of cultured intact human ganglia. J Virol 81:6752–6756. doi: 10.1128/JVI.02793-06 PubMedCrossRefGoogle Scholar
  33. Gowrishankar K, Steain M, Cunningham AL, Rodriguez M, Blumbergs P, Slobedman B, Abendroth A (2010) Characterization of the host immune response in human ganglia after herpes zoster. J Virol 84:8861–8870. doi: 10.1128/JVI.01020-10 PubMedCrossRefGoogle Scholar
  34. Haanpaa M (2009) Controlled release oxycodone—an evidence-based treatment for pain in acute herpes zoster. Pain 142:175–176. doi: 10.1016/j.pain.2009.01.025 PubMedCrossRefGoogle Scholar
  35. Habran L, El MN, Di Valentin E, Sadzot-Delvaux C, Bontems S, Piette J (2007) The varicella-zoster virus immediate-early 63 protein affects chromatin-controlled gene transcription in a cell-type dependent manner. BMC Mol Biol 8:99. doi: 10.1186/1471-2199-8-99 PubMedCrossRefGoogle Scholar
  36. Hama Y, Shiraki K, Yoshida Y, Maruyama A, Yasuda M, Tsuda M, Honda M, Takahashi M, Higuchi H, Takasaki I, Daikoku T, Tsumoto T (2010) Antibody to varicella-zoster virus immediate-early protein 62 augments allodynia in zoster via brain-derived neurotrophic factor. J Virol 84:1616–1624. doi: 10.1128/JVI.02061-09 PubMedCrossRefGoogle Scholar
  37. Hasnie FS, Breuer J, Parker S, Wallace V, Blackbeard J, Lever I, Kinchington PR, Dickenson AH, Pheby T, Rice AS (2007) Further characterization of a rat model of varicella zoster virus-associated pain: relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs. Neuroscience 144:1495–1508. doi: 10.1016/j.neuroscience.2006.11.029 PubMedCrossRefGoogle Scholar
  38. Hempenstall K, Nurmikko TJ, Johnson RW, A’Hern RP, Rice AS (2005) Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med 2:e164. doi: 10.1371/journal.pmed.0020164 PubMedCrossRefGoogle Scholar
  39. Hope-Simpson RE (1965) The nature of herpes zoster: a long-term study and a new hypothesis. Proc R Soc Med 58:9–20PubMedGoogle Scholar
  40. Jensen-Dahm C, Rowbotham MC, Reda H, Petersen KL (2011) Effect of a single dose of pregabalin on herpes zoster pain. Trials 12:55. doi: 10.1186/1745-6215-12-55 PubMedCrossRefGoogle Scholar
  41. Johnson RW, Bouhassira D, Kassianos G, Leplege A, Schmader KE, Weinke T (2010) The impact of herpes zoster and post-herpetic neuralgia on quality-of-life. BMC Med 8:37. doi: 10.1186/1741-7015-8-37 PubMedCrossRefGoogle Scholar
  42. Kennedy PG, Cohrs RJ (2010) Varicella-zoster virus human ganglionic latency: a current summary. J Neurovirol 16:411–418. doi: 10.3109/13550284.2010.515652 PubMedGoogle Scholar
  43. Kress M, Fickenscher H (2001) Infection by human varicella-zoster virus confers norepinephrine sensitivity to sensory neurons from rat dorsal root ganglia. FASEB J 15:1037–1043PubMedCrossRefGoogle Scholar
  44. Ku CC, Besser J, Abendroth A, Grose C, Arvin AM (2005) Varicella-zoster virus pathogenesis and immunobiology: new concepts emerging from investigations with the SCIDhu mouse model. J Virol 79:2651–2658. doi: 10.1128/JVI.79.5.2651-2658.2005 PubMedCrossRefGoogle Scholar
  45. Li Q, Chen N, Yang J, Zhou M, Zhou D, Zhang Q, He L (2009) Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev:CD006866. doi: 10.1002/14651858.CD006866.pub2
  46. Lowry PW, Solem S, Watson BN, Koropchak CM, Thackray HM, Kinchington PR, Ruyechan WT, Ling P, Hay J, Arvin AM (1992) Immunity in strain 2 guinea-pigs inoculated with vaccinia virus recombinants expressing varicella-zoster virus glycoproteins I, IV, V or the protein product of the immediate early gene 62. J Gen Virol 73(Pt 4):811–819PubMedCrossRefGoogle Scholar
  47. Lungu O, Panagiotidis CA, Annunziato PW, Gershon AA, Silverstein SJ (1998) Aberrant intracellular localization of varicella-zoster virus regulatory proteins during latency. Proc Natl Acad Sci U S A 95:7080–7085PubMedCrossRefGoogle Scholar
  48. Mareedu J, Hanumaiah RG, Hale E, Habte-Gabr E (2011) Varicella zoster vasculopathy. J Int Assoc Physicians AIDS Care (Chic) 10:144–145. doi: 10.1177/1545109710397366 CrossRefGoogle Scholar
  49. Markus A, Grigoryan S, Sloutskin A, Yee MB, Zhu H, Yang IH, Thakor NV, Sarid R, Kinchington PR, Goldstein RS (2011) Varicella-zoster virus (VZV) infection of neurons derived from human embryonic stem cells: direct demonstration of axonal infection, transport of VZV, and productive neuronal infection. J Virol 85:6220–6233. doi: 10.1128/JVI.02396-10 PubMedCrossRefGoogle Scholar
  50. McDonald JR, Zeringue AL, Caplan L, Ranganathan P, Xian H, Burroughs TE, Fraser VJ, Cunningham F, Eisen SA (2009) Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis. Clin Infect Dis 48:1364–1371. doi: 10.1086/598331 PubMedCrossRefGoogle Scholar
  51. Medhurst SJ, Collins SD, Billinton A, Bingham S, Dalziel RG, Brass A, Roberts JC, Medhurst AD, Chessell IP (2008) Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain. Pain 138:61–69. doi: 10.1016/j.pain.2007.11.006 PubMedCrossRefGoogle Scholar
  52. Moffat J, Ku CC, Zerboni L, Sommer M, Arvin A (2007) VZV: pathogenesis and the disease consequences of primary infection. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K (eds) Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge University Press, CambridgeGoogle Scholar
  53. Myers MG, Stanberry LR (1991) Drug testing for activity against varicella-zoster virus in hairless guinea pigs. Antiviral Res 15:341–344PubMedCrossRefGoogle Scholar
  54. Nagel MA, Traktinskiy I, Azarkh Y, Kleinschmidt-DeMasters B, Hedley-Whyte T, Russman A, VanEgmond EM, Stenmark K, Frid M, Mahalingam R, Wellish M, Choe A, Cordery-Cotter R, Cohrs RJ, Gilden D (2011) Varicella zoster virus vasculopathy: analysis of virus-infected arteries. Neurology 77:364–370. doi: 10.1212/WNL.0b013e3182267bfa PubMedCrossRefGoogle Scholar
  55. Oxman MN (2009) Herpes zoster pathogenesis and cell-mediated immunity and immunosenescence. J Am Osteopath Assoc 109:S13–S17PubMedGoogle Scholar
  56. Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271–2284. doi: 10.1056/NEJMoa051016 PubMedCrossRefGoogle Scholar
  57. Pavan-Langston D (2008) Herpes zoster antivirals and pain management. Ophthalmology 115:S13–S20. doi: 10.1016/j.ophtha.2007.10.012 PubMedCrossRefGoogle Scholar
  58. Philip A, Thakur R (2011) Post herpetic neuralgia. J Palliat Med 14:765–773. doi: 10.1089/jpm.2011.9685 PubMedCrossRefGoogle Scholar
  59. Pickering G, Leplege A (2011) Herpes zoster pain, postherpetic neuralgia, and quality of life in the elderly. Pain Pract 11:397–402. doi: 10.1111/j.1533-2500.2010.00432.x PubMedCrossRefGoogle Scholar
  60. Pugazhenthi S, Nair S, Velmurugan K, Liang Q, Mahalingam R, Cohrs RJ, Nagel MA, Gilden D (2011) Varicella-zoster virus infection of differentiated human neural stem cells. J Virol 85:6678–6686. doi: 10.1128/JVI.00445-11 PubMedCrossRefGoogle Scholar
  61. Raja SN, Haythornthwaite JA, Pappagallo M, Clark MR, Travison TG, Sabeen S, Royall RM, Max MB (2002) Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 59:1015–1021PubMedGoogle Scholar
  62. Reichelt M, Zerboni L, Arvin AM (2008) Mechanisms of varicella-zoster virus neuropathogenesis in human dorsal root ganglia. J Virol 82:3971–3983. doi: 10.1128/JVI.02592-07 PubMedCrossRefGoogle Scholar
  63. Reynolds MA, Chaves SS, Harpaz R, Lopez AS, Seward JF (2008) The impact of the varicella vaccination program on herpes zoster epidemiology in the United States: a review. J Infect Dis 197(Suppl 2):S224–S227. doi: 10.1086/522162 PubMedCrossRefGoogle Scholar
  64. Rogawski MA, Loscher W (2004) The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat Med 10:685–692. doi: 10.1038/nm1074 PubMedCrossRefGoogle Scholar
  65. Rowbotham MC, Yosipovitch G, Connolly MK, Finlay D, Forde G, Fields HL (1996) Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 3:205–214. doi: 10.1006/nbdi.1996.0021 PubMedCrossRefGoogle Scholar
  66. Schmader K, George LK, Burchett BM, Pieper CF, Hamilton JD (1995) Racial differences in the occurrence of herpes zoster. J Infect Dis 171:701–704PubMedCrossRefGoogle Scholar
  67. Sen N, Sommer M, Che X, White K, Ruyechan WT, Arvin AM (2010) Varicella-zoster virus immediate-early protein 62 blocks interferon regulatory factor 3 (IRF3) phosphorylation at key serine residues: a novel mechanism of IRF3 inhibition among herpesviruses. J Virol 84:9240–9253. doi: 10.1128/JVI.01147-10 PubMedCrossRefGoogle Scholar
  68. Seward JF, Marin M, Vazquez M (2008) Varicella vaccine effectiveness in the US vaccination program: a review. J Infect Dis 197(Suppl 2):S82–S89. doi: 10.1086/522145 PubMedCrossRefGoogle Scholar
  69. Steain M, Slobedman B, Abendroth A (2010) Experimental models to study varicella-zoster virus infection of neurons. Curr Top Microbiol Immunol 342:211–228. doi: 10.1007/82_2010_15 PubMedCrossRefGoogle Scholar
  70. Steiner I, Kennedy PG, Pachner AR (2007) The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 6:1015–1028. doi: 10.1016/S1474-4422(07)70267-3 PubMedCrossRefGoogle Scholar
  71. Thomas SL, Wheeler JG, Hall AJ (2004) Case–control study of the effect of mechanical trauma on the risk of herpes zoster. BMJ 328:439. doi: 10.1136/bmj.37991.511829.F7 PubMedCrossRefGoogle Scholar
  72. Tischer BK, Kaufer BB, Sommer M, Wussow F, Arvin AM, Osterrieder N (2007) A self-excisable infectious bacterial artificial chromosome clone of varicella-zoster virus allows analysis of the essential tegument protein encoded by ORF9. J Virol. 81(23):13200–13208. Epub 2007 Oct 3. PubMed PMID: 17913822; PubMed Central PMCID: PMC2169085.Google Scholar
  73. Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ (2000) Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med 9:863–869PubMedCrossRefGoogle Scholar
  74. Verjans GM, Hintzen RQ, van Dun JM, Poot A, Milikan JC, Laman JD, Langerak AW, Kinchington PR, Osterhaus AD (2007) Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia. Proc Natl Acad Sci U S A 104:3496–3501. doi: 10.1073/pnas.0610847104 PubMedCrossRefGoogle Scholar
  75. Wallace VC, Segerdahl AR, Lambert DM, Vandevoorde S, Blackbeard J, Pheby T, Hasnie F, Rice AS (2007) The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. Br J Pharmacol 151:1117–1128. doi: 10.1038/sj.bjp.0707326 PubMedCrossRefGoogle Scholar
  76. Watson CP, Morshead C, Van der Kooy D, Deck J, Evans RJ (1988) Post-herpetic neuralgia: post-mortem analysis of a case. Pain 34:129–138PubMedCrossRefGoogle Scholar
  77. White K, Peng H, Hay J, Ruyechan WT (2010) Role of the IE62 consensus binding site in transactivation by the varicella-zoster virus IE62 protein. J Virol 84:3767–3779. doi: 10.1128/JVI.02522-09 PubMedCrossRefGoogle Scholar
  78. Yeomans DC, Wilson SP (2009) Herpes virus-based recombinant herpes vectors: gene therapy for pain and molecular tool for pain science. Gene Ther 16:502–508. doi: 10.1038/gt.2009.25 PubMedCrossRefGoogle Scholar
  79. Zerboni L, Reichelt M, Arvin A (2010a) Varicella-zoster virus neurotropism in SCID mouse–human dorsal root ganglia xenografts. Curr Top Microbiol Immunol 342:255–276. doi: 10.1007/82_2009_8 PubMedCrossRefGoogle Scholar
  80. Zerboni L, Sobel RA, Ramachandran V, Rajamani J, Ruyechan W, Abendroth A, Arvin A (2010b) The expression of varicella-zoster virus immediate early regulatory protein IE63 in neurons of latently infected human sensory ganglia. J Virol. doi: 10.1128/JVI.02416-09
  81. Zerboni L, Sobel RA, Lai M, Triglia R, Steain M, Abendroth A, Arvin A (2011) Apparent expression of varicella-zoster virus proteins in latency resulting from reactivity of murine and rabbit antibodies with human blood group A determinants in sensory neurons. J Virol. doi: 10.1128/JVI.05950-11
  82. Zuranski T, Nawar H, Czechowski D, Lynch JM, Arvin A, Hay J, Ruyechan WT (2005) Cell-type-dependent activation of the cellular EF-1alpha promoter by the varicella-zoster virus IE63 protein. Virology 338:35–42. doi: 10.1016/j.virol.2005.05.005 PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2011

Authors and Affiliations

  1. 1.Department of OphthalmologyUniversity of PittsburghPittsburghUSA
  2. 2.Department of Microbiology and Molecular GeneticsUniversity of PittsburghPittsburghUSA

Personalised recommendations