Abstract
Reactivation of latent varicella-zoster virus (VZV) causes herpes zoster (HZ), which is commonly accompanied by acute pain and pruritus over the time course of a zosteriform rash. Although the rash and associated pain are self-limiting, a considerable fraction of HZ cases will subsequently develop debilitating chronic pain states termed postherpetic neuralgia (PHN). How VZV causes acute pain and the mechanisms underlying the transition to PHN are far from clear. The human-specific nature of VZV has made in vivo modeling of pain following reactivation difficult to study because no single animal can reproduce reactivated VZV disease as observed in the clinic. Investigations of VZV pathogenesis following primary infection have benefited greatly from human tissues harbored in immune-deficient mice, but modeling of acute and chronic pain requires an intact nervous system with the capability of transmitting ascending and descending sensory signals. Several groups have found that subcutaneous VZV inoculation of the rat induces prolonged and measurable changes in nociceptive behavior, indicating sensitivity that partially mimics the development of mechanical allodynia and thermal hyperalgesia seen in HZ and PHN patients. Although it is not a model of reactivation, the rat is beginning to inform how VZV infection can evoke a pain response and induce long-lasting alterations to nociception. In this review, we will summarize the rat pain models from a practical perspective and discuss avenues that have opened for testing of novel treatments for both zoster-associated pain and chronic PHN conditions, which remain in critical need of effective therapies.
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References
Acosta EP, Balfour HH (2001) Acyclovir for treatment of postherpetic neuralgia: efficacy and pharmacokinetics. Antimicrob Agents Chemother 45:2771–2774. https://doi.org/10.1128/AAC.45.10.2771-2774.2001
Ahmed SV, Hamada H, Jayawarna C, Chandra S (2012) Shingles with secondary asymptomatic CNS involvement! Case Rep bcr0320126041–bcr0320126041. https://doi.org/10.1136/bcr.03.2012.6041
Amicizia D, Domnich A, Arata L et al (2017) The role of age-sex interaction in the development of post-herpetic neuralgia. Hum Vaccines Immunother 13:376–378. https://doi.org/10.1080/21645515.2017.1264799
Annunziato P, LaRussa P, Lee P et al (1998) Evidence of latent varicella-zoster virus in rat dorsal root ganglia. J Infect Dis 178(Suppl):S48-51. https://doi.org/10.1086/514261
Aoto J, Földy C, Ilcus SMC et al (2015) Distinct circuit-dependent functions of presynaptic neurexin-3 at GABAergic and glutamatergic synapses. Nat Neurosci 18:997–1007. https://doi.org/10.1038/nn.4037
Baiker A, Fabel K, Cozzio A et al (2004) Varicella-zoster virus infection of human neural cells in vivo. Proc Natl Acad Sci U S A 101:10792–10797. https://doi.org/10.1073/pnas.0404016101
Benbernou A, Drolet M, Levin MJ et al (2011) Association between prodromal pain and the severity of acute herpes zoster and utilization of health care resources. Eur J Pain 15:1100–1106. https://doi.org/10.1016/j.ejpain.2011.04.014
Bharucha T, Ming D, Breuer J (2017) A critical appraisal of “Shingrix”, a novel herpes zoster subunit vaccine (HZ/Su or GSK1437173A) for varicella zoster virus. Hum Vaccin Immunother 13:1789–1797. https://doi.org/10.1080/21645515.2017.1317410
Borkar DS, Tham VM, Esterberg E et al (2013) Incidence of herpes zoster ophthalmicus: results from the Pacific ocular inflammation study. Ophthalmology 120:451–456. https://doi.org/10.1016/j.ophtha.2012.09.007
Braz J, Beaufour C, Coutaux A et al (2001) Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons. J Neurosci 21:7881–7888. https://doi.org/10.1523/JNEUROSCI.21-20-07881.2001
Bushnell MC, Čeko M, Low LA (2013) Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci 14:502–511. https://doi.org/10.1038/nrn3516
Chaplan SR, Bach FW, Pogrel JW et al (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63. https://doi.org/10.1016/0165-0270(94)90144-9
Chen F, Chen F, Shang Z et al (2017) White matter microstructure degenerates in patients with postherpetic neuralgia. Neurosci Lett 656:152–157. https://doi.org/10.1016/j.neulet.2017.07.023
Chen N, Li Q, Yang J et al (2014) Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev CD006866. https://doi.org/10.1002/14651858.CD006866.pub3
Cohen JI (2010) Rodent models of varicella-zoster virus neurotropism. Curr Top Microbiol Immunol 342:277–289. https://doi.org/10.1007/82_2010_11
Cunningham AL, Heineman T (2017) Vaccine profile of herpes zoster (HZ/su) subunit vaccine. Expert Rev Vaccines 16:661–670. https://doi.org/10.1080/14760584.2017.1329012
Cunningham AL, Heineman TC, Lal H et al (2018) Immune responses to a recombinant glycoprotein E herpes zoster vaccine in adults aged 50 years or older. J Infect Dis 217:1750–1760. https://doi.org/10.1093/infdis/jiy095
Dalziel RG, Bingham S, Sutton D et al (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. https://doi.org/10.1016/j.brainresrev.2004.07.008
De Jong MD, Weel JFL, Schuurman T et al (2000) Quantitation of varicella-zoster virus DNA in whole blood, plasma, and serum by PCR and electrochemiluminescence. J Clin Microbiol 38:2568–2573. https://doi.org/10.1128/jcm.38.7.2568-2573.2000
Debrus S, Sadzot-Delvaux C, Nikkels AF et al (1995) Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency. J Virol 69:3240–3245. https://doi.org/10.1128/JVI.69.5.3240-3245.1995
Decosterd I, Ji RR, Abdi S et al (2002) The pattern of expression of the voltage-gated sodium channels Nav1.8 and Nav1.9 does not change in uninjured primary sensory neurons in experimental neuropathic pain models. Pain 96:269–277. https://doi.org/10.1016/S0304-3959(01)00456-0
Defechereux P, Debrus S, Baudoux L et al (1997) Varicella-zoster virus open reading frame 4 encodes an immediate-early protein with posttranscriptional regulatory properties. J Virol 71:7073–7079. https://doi.org/10.1128/JVI.71.9.7073-7079.1997
Delaney A, Colvin LA, Fallon MT et al (2009) Postherpetic neuralgia: from preclinical models to the clinic. Neurotherapeutics 6:630–7. https://doi.org/10.1016/j.nurt.2009.07.005
Detloff MR, Fisher LC, Deibert RJ, Basso DM (2012) Acute and chronic tactile sensory testing after spinal cord injury in rats. J Vis Exp e3247. https://doi.org/10.3791/3247
Devor M (2018) Rethinking the causes of pain in herpes zoster and postherpetic neuralgia: the ectopic pacemaker hypothesis. PAIN Reports 3:e702. https://doi.org/10.1097/PR9.0000000000000702
Dooling KL, Guo A, Patel M et al (2018) Recommendations of the advisory committee on immunization practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep 67:103–108. https://doi.org/10.15585/mmwr.mm6703a5
Drolet M, Brisson M, Schmader KE et al (2010) The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: a prospective study. C Can Med Assoc J 182:1731–1736. https://doi.org/10.1503/cmaj.091711
Dworkin RH, Johnson RW, Breuer J et al (2007) Recommendations for the management of herpes zoster. Clin Infect Dis 44:S1–S26. https://doi.org/10.1086/510206
Dworkin RH, Nagasako EM, Johnson RW, Griffin DRJ (2001) Acute pain in herpes zoster: the famciclovir database project. Pain 94:113–119. https://doi.org/10.1016/S0304-3959(01)00347-5
Elion GB (1983) The biochemistry and mechanism of action of acyclovir. J Antimicrob Chemother 12:9–17. https://doi.org/10.1093/jac/12.suppl_b.9
Esposito S, Franco E, Gavazzi G et al (2018) The public health value of vaccination for seniors in Europe. Vaccine 36:2523–2528. https://doi.org/10.1016/j.vaccine.2018.03.053
Fink DJ, Wechuck J, Mata M et al (2011) Gene therapy for pain: results of a phase I clinical trial. Ann Neurol 70:207–212. https://doi.org/10.1002/ana.22446
Finnen RL, Mizokami KR, Banfield BW et al (2006) Postentry events are responsible for restriction of productive varicella-zoster virus infection in chinese hamster ovary cells. J Virol 80:10325–10334. https://doi.org/10.1128/JVI.00939-06
Fleetwood-Walker SM, Quinn JP, Wallace C et al (1999) Behavioural changes in the rat following infection with varicella-zoster virus. J Gen Virol 80(Pt 9):2433–2436. https://doi.org/10.1099/0022-1317-80-9-2433
Forbes HJ, Bhaskaran K, Thomas SL et al (2014) Quantification of risk factors for herpes zoster: population based case-control study. BMJ 348:g2911. https://doi.org/10.1136/bmj.g2911
Forbes HJ, Bhaskaran K, Thomas SL et al (2016a) Quantification of risk factors for postherpetic neuralgia in herpes zoster patients. Neurology 87:94–102. https://doi.org/10.1212/WNL.0000000000002808
Forbes HJ, Thomas SL, Smeeth L et al (2016b) A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain 157:30–54. https://doi.org/10.1097/j.pain.0000000000000307
Fuchs PN, McNabb CT (2012) The place escape/avoidance paradigm: a novel method to assess nociceptive processing. J Integr Neurosci 11:61–72. https://doi.org/10.1142/S0219635212500045
Furuta Y, Takasu T, Fukuda S et al (1992) Detection of varicella-zoster virus DNA in human geniculate ganglia by polymerase chain reaction. J Infect Dis 166:1157–1159. https://doi.org/10.1093/infdis/166.5.1157
Furuta Y, Takasu T, Suzuki S et al (1997) Detection of latent varicella-zoster virus infection in human vestibular and spiral ganglia. J Med Virol 51:214–216. https://doi.org/10.1002/(SICI)1096-9071(199703)51:3%3c214::AID-JMV12%3e3.0.CO;2-K
Garry EM, Delaney A, Anderson HA et al (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. https://doi.org/10.1016/j.pain.2005.08.003
Gershon AA, Breuer J, Cohen JI et al (2015) Varicella zoster virus infection. Nat Rev Dis Prim 1:1–19. https://doi.org/10.1038/nrdp.2015.16
Gershon AA, Chen J, Davis L et al (2012) Latency of varicella zoster virus in dorsal root, cranial, and enteric ganglia in vaccinated children. Trans Am Clin Climatol Assoc 123:17–35
Gilden DH, Gesser R, Smith J et al (2001) Presence of VZV and HSV-1 DNA in human nodose and celiac ganglia. Virus Genes 23:145–147. https://doi.org/10.1023/a:1011883919058
Goh CL, Khoo L (1997) A retrospective study of the clinical presentation and outcome of herpes zoster in a tertiary dermatology outpatient referral clinic. Int J Dermatol 36:667–672. https://doi.org/10.1046/j.1365-4362.1997.00241.x
Gold MS, Weinreich D, Kim CS et al (2003) Redistribution of Nav1.8 in uninjured axons enables neuropathic pain. J Neurosci 23:158–166. https://doi.org/10.1523/jneurosci.23-01-00158.2003
Goss JR, Mata M, Goins WF et al (2001) Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther 8:551–556. https://doi.org/10.1038/sj.gt.3301430
Gowrishankar K, Steain M, Cunningham AL et al (2010) Characterization of the host immune response in human Ganglia after herpes zoster. J Virol 84:8861–8870. https://doi.org/10.1128/JVI.01020-10
Gray WL (2010) Simian varicella virus: molecular virology. In: Current topics in microbiology and immunology, pp 291–308
Grinfeld E, Sadzot-Delvaux C, Kennedy PGE (2004) Varicella-Zoster virus proteins encoded by open reading frames 14 and 67 are both dispensable for the establishment of latency in a rat model. Virology 323:85–90. https://doi.org/10.1016/j.virol.2004.02.020
Guedon J-MG, Zhang M, Glorioso JC et al (2014) Relief of pain induced by varicella-zoster virus in a rat model of post-herpetic neuralgia using a herpes simplex virus vector expressing enkephalin. Gene Ther 21:694–702. https://doi.org/10.1038/gt.2014.43
Guedon J-MG, Wu S, Zheng X et al (2015a) Current gene therapy using viral vectors for chronic pain. Mol Pain 11:s12990-015–0018. https://doi.org/10.1186/s12990-015-0018-1
Guedon J-MG, Yee MB, Zhang M et al (2015b) Neuronal changes induced by Varicella Zoster Virus in a rat model of postherpetic neuralgia. Virology 482:167–180. https://doi.org/10.1016/j.virol.2015.03.046
Haanpää M, Laippala P, Nurmikko T (1999) Pain and somatosensory dysfunction in acute herpes zoster. Clin J Pain 15:78–84. https://doi.org/10.1097/00002508-199906000-00003
Haanpää M, Laippala P, Nurmikko T (2000) Allodynia and pinprick hypesthesia in acute herpes zoster, and the development of postherpetic neuralgia. J Pain Symptom Manage 20:50–58. https://doi.org/10.1016/S0885-3924(00)00149-4
Haargaard B, Lund-andersen H, Milea D (2008) Central nervous system involvement after herpes zoster ophthalmicus. Acta Ophthalmol 86:806–809. https://doi.org/10.1111/j.1600-0420.2007.01129.x
Haberthur K, Messaoudi I (2013) Animal models of varicella zoster virus infection. Pathog (basel, Switzerland) 2:364–382. https://doi.org/10.3390/pathogens2020364
Hao S, Mata M, Wolfe D et al (2003) HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain. Mol Ther 8:367–375. https://doi.org/10.1016/S1525-0016(03)00185-0
Hao S, Mata M, Fink DJ (2007) Viral vector-based gene transfer for treatment of chronic pain. Int Anesthesiol Clin 45:59–71. https://doi.org/10.1097/AIA.0b013e318034199c
Hao S, Hu J, Fink DJ (2009) Transgene-mediated enkephalin expression attenuates signs of naloxone-precipitated morphine withdrawal in rats with neuropathic pain. Behav Brain Res 197:84–89. https://doi.org/10.1016/j.bbr.2008.08.005
Hargreaves K, Dubner R, Brown F et al (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88. https://doi.org/10.1016/0304-3959(88)90026-7
Hasnie FS, Breuer J, Parker S et al (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. https://doi.org/10.1016/j.neuroscience.2006.11.029
Hassan S, Cohen PR (2019) Postherpetic pruritus: a potential complication of Herpes Zoster Virus Infection. Cureus 11. https://doi.org/10.7759/cureus.5665
Hope-Simpson R (1965) The nature of Herpes Zoster: a long-term study and a new hypothesis. Proc R Soc Med 58:9–20. https://doi.org/10.1177/003591576505800106
Hope-Simpson R (1975) Postherpetic neuralgia. J R Coll Gen Pract 25:571–575. https://doi.org/10.1017/CBO9781107281950.002
Hornung R, Pritchard A, Kinchington PR, Kramer PR (2020a) Reduced activity of GAD67 expressing cells in the reticular thalamus enhance thalamic excitatory activity and varicella zoster virus associated pain. Neurosci Lett 736:135287. https://doi.org/10.1016/j.neulet.2020.135287
Hornung R, Pritchard A, Kinchington PR, Kramer PR (2020b) Comparing gene expression in the parabrachial and amygdala of diestrus and proestrus female rats after orofacial Varicella Zoster injection. Int J Mol Sci 21:5749. https://doi.org/10.3390/ijms21165749
Igarashi H, Koizumi K, Kaneko R et al (2016) A novel reporter rat strain that conditionally expresses the bright red fluorescent protein tdTomato. PLoS ONE 11:e0155687. https://doi.org/10.1371/journal.pone.0155687
Ito M, Nishihara H, Mizutani et al (1995) Detection of varicella-zoster virus (VZV) DNA in throat swabs and peripheral blood mononuclear cells of immunocompromised patients with herpes zoster by polymerase chain reaction. Clin Diagn Virol 4:105–112. https://doi.org/10.1016/0928-0197(94)00061-X
Iwamoto M, Björklund T, Lundberg C et al (2010) A general chemical method to regulate protein stability in the mammalian central nervous system. Chem Biol 17:981–988. https://doi.org/10.1016/j.chembiol.2010.07.009
Jaggi AS, Jain V, Singh N (2011) Animal models of neuropathic pain. Fundam Clin Pharmacol 25:1–28. https://doi.org/10.1111/j.1472-8206.2009.00801.x
Jarvis MF, Honore P, Shieh CC et al (2007) A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci USA 104:8520–8525. https://doi.org/10.1073/pnas.0611364104
Ji R-R, Chamessian A, Zhang Y-Q (2016) Pain regulation by non-neuronal cells and inflammation. Science (80–)354:572–577. https://doi.org/10.1126/science.aaf8924
Jones JO, Arvin AM (2003) Microarray analysis of host cell gene transcription in response to varicella-zoster virus infection of human T cells and fibroblasts in vitro and SCIDhu skin xenografts in vivo. J Virol 77:1268–1280. https://doi.org/10.1128/jvi.77.2.1268-1280.2003
Jung BF, Johnson RW, Griffin DRJ, Dworkin RH (2004) Risk factors for postherpetic neuralgia in patients with herpes zoster. Neurology 62:1545–1551. https://doi.org/10.1212/01.WNL.0000123261.00004.29
Kawai K, Gebremeskel BG, Acosta CJ (2014) Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open 4:e004833. https://doi.org/10.1136/bmjopen-2014-004833
Kennedy PGE (2011) Zoster sine herpete: It would be rash to ignore it. Neurology 76:416–417. https://doi.org/10.1212/WNL.0b013e31820a0d5d
Kennedy PGE, Gershon AA (2018) Clinical features of varicella-zoster virus infection. Viruses 10:1–11. https://doi.org/10.3390/v10110609
Kennedy PGE, Grinfeld E, Bontems S, Sadzot-Delvaux C (2001) Varicella-Zoster virus gene expression in latently infected rat dorsal root ganglia. Virology 289:218–223. https://doi.org/10.1006/viro.2001.1173
Kim CH, Oh Y, Chung JM, Chung K (2001) The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation. Mol Brain Res 95:153–161. https://doi.org/10.1016/S0169-328X(01)00226-1
Kinchington PR, Goins WF (2011) Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models. J Neurovirol 17:590–599. https://doi.org/10.1007/s13365-011-0069-7
Kollias CM, Huneke RB, Wigdahl B, Jennings SR (2015) Animal models of herpes simplex virus immunity and pathogenesis. J Neurovirol 21:8–23. https://doi.org/10.1007/s13365-014-0302-2
Kramer PR, Bellinger LL (2009) The effects of cycling levels of 17beta-estradiol and progesterone on the magnitude of temporomandibular joint-induced nociception. Endocrinology 150:3680–3689. https://doi.org/10.1210/en.2008-1707
Kramer PR, Strand J, Stinson C et al (2017) Role for the ventral posterior medial/posterior lateral thalamus and anterior cingulate cortex in affective/motivation pain induced by varicella zoster virus. Front Integr Neurosci 11:27. https://doi.org/10.3389/fnint.2017.00027
Kramer P, Rao M, Stinson C et al (2018) Aromatase derived estradiol within the thalamus modulates pain induced by varicella zoster virus. Front Integr Neurosci 12:1–14. https://doi.org/10.3389/fnint.2018.00046
Ku C-C, Besser J, Abendroth A et al (2005) Varicella-Zoster virus pathogenesis and immunobiology: new concepts emerging from investigations with the SCIDhu mouse model. J Virol 79:2651–2658. https://doi.org/10.1128/JVI.79.5.2651-2658.2005
Ku C-C, Zerboni L, Ito H et al (2004) Varicella-zoster virus transfer to skin by T Cells and modulation of viral replication by epidermal cell interferon-alpha. J Exp Med 200:917–925. https://doi.org/10.1084/jem.20040634
Lal H, Cunningham AL, Godeaux O et al (2015) Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med 372:2087–2096. https://doi.org/10.1056/NEJMoa1501184
Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10:895–926. https://doi.org/10.1016/j.jpain.2009.06.012
Laval K, Enquist LW (2020) The neuropathic itch caused by pseudorabies virus. Pathogens 9. https://doi.org/10.3390/pathogens9040254
Laval K, Vernejoul JB, Van Cleemput J et al (2018) Virulent pseudorabies virus infection induces a specific and lethal systemic inflammatory response in mice. J Virol 92. https://doi.org/10.1128/JVI.01614-18
Lewis DJ, Schlichte MJ, Dao H (2017) Atypical disseminated herpes zoster: management guidelines in immunocompromised patients. Cutis 100:321; 324; 330
Liesegang TJ (2008) Herpes zoster ophthalmicus. natural history, risk factors, clinical presentation, and morbidity. Ophthalmology 115:3–12. https://doi.org/10.1016/j.ophtha.2007.10.009
Lindia JA, Köhler MG, Martin WJ, Abbadie C (2005) Relationship between sodium channel NaV1.3 expression and neuropathic pain behavior in rats. Pain 117:145–153. https://doi.org/10.1016/j.pain.2005.05.027
Luo ZD, Calcutt NA, Higuera ES et al (2002) Injury type-specific calcium channel α2δ-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther 303:1199–1205. https://doi.org/10.1124/jpet.102.041574
Magnussen C, Hung S-P, Ribeiro-da-Silva A (2015) Novel expression pattern of neuropeptide Y immunoreactivity in the peripheral nervous system in a rat model of neuropathic pain. Mol Pain 11:31. https://doi.org/10.1186/s12990-015-0029-y
Mahalingam R, Wellish M, Brucklier J, Gilden DH (1995) Persistence of varicella-zoster virus DNA in elderly patients with postherpetic neuralgia. J Neurovirol 1:130–133. https://doi.org/10.3109/13550289509111018
Mahalingam R, Wellish M, Soike K et al (2001) Simian varicella virus infects ganglia before rash in experimentally infected monkeys. Virology 279:339–342. https://doi.org/10.1006/viro.2000.0700
Mahalingam R, Gershon A, Gershon M et al (2019) Current In Vivo Models of Varicella-Zoster Virus Neurotropism. Viruses 11:502. https://doi.org/10.3390/v11060502
Mainka C, Fuß B, Geiger H et al (1998) Characterization of viremia at different stages of Varicella-zoster virus infection. J Med Virol 56:91–98. https://doi.org/10.1002/(SICI)1096-9071(199809)56:1%3c91::AID-JMV15%3e3.0.CO;2-Z
Maratou K, Wallace VCJ, Hasnie FS et al (2009) Comparison of dorsal root ganglion gene expression in rat models of traumatic and HIV-associated neuropathic pain. Eur J Pain 13:387–398. https://doi.org/10.1016/j.ejpain.2008.05.011
Marin M, Güris D, Chaves SS et al (2007) Prevention of varicella: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Reports Morb Mortal Wkly Report Recomm Reports 56:1–40
McIntire SL, Reimer RJ, Schuske K et al (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876. https://doi.org/10.1038/39908
Medhurst SJ, Collins SD, Billinton A et al (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. https://doi.org/10.1016/j.pain.2007.11.006
Meunier A, Latrémolière A, Mauborgne A et al (2005) Attenuation of pain-related behavior in a rat model of trigeminal neuropathic pain by viral-driven enkephalin overproduction in trigeminal ganglion neurons. Mol Ther 11:608–616. https://doi.org/10.1016/j.ymthe.2004.12.011
Meyer-Rosberg K, Kvarnström A, Kinnman E et al (2001) Peripheral neuropathic pain—a multidimensional burden for patients. Eur J Pain 5:379–389. https://doi.org/10.1053/eujp.2001.0259
Muñoz-Quiles C, López-Lacort M, Orrico-Sánchez A, Díez-Domingo J (2018) Letter to the editor regarding “The role of age-sex interaction in the development of post-herpetic neuralgia.” Hum Vaccines Immunother 14:906–908. https://doi.org/10.1080/21645515.2017.1417715
Nagel MA, Rempel A, Huntington J et al (2014) Frequency and abundance of Alphaherpesvirus DNA in human thoracic sympathetic ganglia. J Virol 88:8189–8192. https://doi.org/10.1128/JVI.01070-14
Oaklander AL (2001) The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. Pain 92:139–145. https://doi.org/10.1016/s0304-3959(00)00481-4
Oaklander AL, Romans K, Horasek S et al (1998) Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage. Ann Neurol 44:789–795. https://doi.org/10.1002/ana.410440513
Oaklander AL, Cohen SP, Raju SVY (2002) Intractable postherpetic itch and cutaneous differentation after facial shingles. Pain 96:9–12. https://doi.org/10.1016/S0304-3959(01)00400-6
Oaklander AL, Bowsher D, Galer B et al (2003) Herpes zoster itch: preliminary epidemiologic data. J Pain 4:338–343. https://doi.org/10.1016/S1526-5900(03)00637-0
Opstelten W, McElhaney J, Weinberger B et al (2010) The impact of varicella zoster virus: chronic pain. J Clin Virol 48(Suppl 1):S8-13. https://doi.org/10.1016/S1386-6532(10)70003-2
Ouwendijk WJD, Flowerdew SE, Wick D et al (2012) Immunohistochemical detection of intra-neuronal VZV proteins in snap-frozen human ganglia is confounded by antibodies directed against blood group A1-associated antigens. J Neurovirol 18:172–180. https://doi.org/10.1007/s13365-012-0095-0
Ouwendijk WJD, Mahalingam R, de Swart RL et al (2013) T-Cell tropism of simian varicella virus during primary infection. PLoS Pathog 9:e1003368. https://doi.org/10.1371/journal.ppat.1003368
Oxman MN, Levin MJ, Johnson GR et al (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271–2284. https://doi.org/10.1056/NEJMoa051016
Oyang EL, Davidson BC, Lee W, Poon MM (2011) Functional characterization of the dendritically localized mRNA neuronatin in hippocampal neurons. PLoS ONE 6:e24879. https://doi.org/10.1371/journal.pone.0024879
Pappagallo M (2003) Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. Clin Ther 25:2506–2538. https://doi.org/10.1016/S0149-2918(03)80314-4
Peng X, Zhou Z, Glorioso JC et al (2006) Tumor necrosis factor-alpha contributes to below-level neuropathic pain after spinal cord injury. Ann Neurol 59:843–851. https://doi.org/10.1002/ana.20855
Petersen KL, Rowbotham MC (2010) Natural history of sensory function after herpes zoster. Pain 150:83–92. https://doi.org/10.1016/j.pain.2010.04.005
Pinto M, Castro AR, Tshudy F et al (2008) Opioids modulate pain facilitation from the dorsal reticular nucleus. Mol Cell Neurosci 39:508–518. https://doi.org/10.1016/j.mcn.2008.07.008
Piret J, Boivin G (2016) Antiviral resistance in herpes simplex virus and varicella-zoster virus infections. Curr Opin Infect Dis 29:654–662. https://doi.org/10.1097/QCO.0000000000000288
Poisbeau P, Aouad M, Gazzo G et al (2019) Cholecalciferol (vitamin D3) reduces rat neuropathic pain by modulating opioid signaling. Mol Neurobiol 56:7208–7221. https://doi.org/10.1007/s12035-019-1582-6
Prochazkova M, Terse A, Amin ND et al (2013) Activation of cyclin-dependent kinase 5 mediates orofacial mechanical hyperalgesia. Mol Pain 9:1–12. https://doi.org/10.1186/1744-8069-9-66
Reichelt M, Zerboni L, Arvin AM (2008) Mechanisms of varicella-zoster virus neuropathogenesis in human dorsal root ganglia. J Virol 82:3971–3983. https://doi.org/10.1128/JVI.02592-07
Riva L, Thiry M, Bontems S et al (2013) ORF9p phosphorylation by ORF47p is crucial for the formation and egress of varicella-zoster virus viral particles. J Virol 87:2868–2881. https://doi.org/10.1128/JVI.02757-12
Rowbotham MC, Fields HL (1996) The relationship of pain, allodynia and thermal sensation in post-herpetic neuralgia. Brain 119:347–354. https://doi.org/10.1093/brain/119.2.347
Rowbotham MC, Yosipovitch G, Connolly MK et al (1996) Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis 3:205–214. https://doi.org/10.1006/nbdi.1996.0021
Rowbotham M, Harden N, Stacey B et al (1998) Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 280:1837–1842. https://doi.org/10.1001/jama.280.21.1837
Sadzot-Delvaux C, Merville-Louis MP, Delrée P et al (1990) An in vivo model of varicella-zoster virus latent infection of dorsal root ganglia. J Neurosci Res 26:83–89. https://doi.org/10.1002/jnr.490260110
Sadzot-Delvaux C, Debrus S, Nikkels A et al (1995) Varicella-zoster virus latency in the adult rat is a useful model for human latent infection. Neurology 45. https://doi.org/10.1212/wnl.45.12_suppl_8.s18
Saint-Leéger E, Caumes E, Breton G et al (2001) Clinical and virologic characterization of acyclovir-resistant varicella-zoster viruses isolated from 11 patients with acquired immunodeficiency syndrome. Clin Infect Dis 33:2061–2067. https://doi.org/10.1086/324503
Sato H, Pesnicak L, Cohen JI (2002) Varicella-Zoster virus open reading frame 2 encodes a membrane phosphoprotein that is dispensable for viral replication and for establishment of latency. J Virol 76:3575–3578. https://doi.org/10.1128/JVI.76.7.3575-3578.2002
Sato H, Pesnicak L, Cohen JI (2003) Use of a rodent model to show that varicella-zoster virus ORF61 is dispensable for establishment of latency. J Med Virol 70. https://doi.org/10.1002/jmv.10326
Schmelz M (2015) Itch and pain differences and commonalities. In: Schaible H-G (ed) Pain control. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 285–301
Schmid DS, Jumaan AO (2010) Impact of varicella vaccine on varicella-zoster virus dynamics. Clin Microbiol Rev 23:202–217
Schünemann S, Mainka C, Wolff MH (1999) No acute varicella-zoster virus replication in peripheral blood mononuclear cells during postherpetic neuralgia. Acta Virol 43:337–340
Schutzer-Weissmann J, Farquhar-Smith P (2017) Post-herpetic neuralgia—a review of current management and future directions. Expert Opin Pharmacother 18:1739–1750. https://doi.org/10.1080/14656566.2017.1392508
Shafran SD, Tyring SK, Ashton R et al (2004) Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: A randomized, multicenter, double-blind clinical trial. J Clin Virol 29:248–253. https://doi.org/10.1016/S1386-6532(03)00164-1
Shiraki K, Toyama N, Shiraki A, Yajima M (2018) Age-dependent trigeminal and female-specific lumbosacral increase in herpes zoster distribution in the elderly. J Dermatol Sci 90:166–171. https://doi.org/10.1016/j.jdermsci.2018.01.009
Silva JR, Lopes AH, Talbot J et al (2017) Neuroimmune–glia interactions in the sensory ganglia account for the development of acute herpetic neuralgia. J Neurosci 37:6408–6422. https://doi.org/10.1523/JNEUROSCI.2233-16.2017
Silva CR, Melo BMSS, Silva JR et al (2020) S100A9 plays a pivotal role in a mouse model of herpetic neuralgia via TLR4/TNF pathway. Brain Behav Immun 88:1–10. https://doi.org/10.1016/j.bbi.2020.03.033
Smith KJ (1991) Acyclovir-resistant varicella zoster responsive to foscarnet. Arch Dermatol 127:1069. https://doi.org/10.1001/archderm.1991.01680060145032
Steain M, Sutherland JP, Rodriguez M et al (2014) Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia. J Virol 88:2704–2716. https://doi.org/10.1128/JVI.03445-13
Stinson C, Deng M, Yee MB et al (2017) Sex differences underlying orofacial varicella zoster associated pain in rats. BMC Neurol 17:95. https://doi.org/10.1186/s12883-017-0882-6
Stinson C, Logan SM, Bellinger LL et al (2019) Estradiol acts in lateral thalamic region to attenuate varicella zoster virus associated affective pain. Neuroscience 414:99–111. https://doi.org/10.1016/j.neuroscience.2019.06.029
Studahl M, Petzold M, Cassel T (2013) Disease burden of herpes zoster in Sweden—predominance in the elderly and in women—a register based study. BMC Infect Dis 13:586. https://doi.org/10.1186/1471-2334-13-586
Sun J, Liu S, Mata M et al (2012) Transgene-mediated expression of tumor necrosis factor soluble receptor attenuates morphine tolerance in rats. Gene Ther 19:101–108. https://doi.org/10.1038/gt.2011.76
Takasaki I, Andoh T, Nitta M et al (2000) Pharmacological and immunohistochemical characterization of a mouse model of acute herpetic pain. Jpn J Pharmacol 83:319–326. https://doi.org/10.1254/jjp.83.319
Takasaki I, Andoh T, Shiraki K, Kuraishi Y (2000) Allodynia and hyperalgesia induced by herpes simplex virus type-1 infection in mice. Pain 86:95–101. https://doi.org/10.1016/s0304-3959(00)00240-2
Tischer BK, Kaufer BB, Sommer M et al (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 81:13200–13208. https://doi.org/10.1128/JVI.01148-07
Tran KD, Falcone MM, Choi DS et al (2016) Epidemiology of herpes Zoster Ophthalmicus recurrence and chronicity. Ophthalmology 123:1469–1475. https://doi.org/10.1016/j.ophtha.2016.03.005
Tseng HF, Harpaz R, Luo Y et al (2016) Declining effectiveness of herpes Zoster vaccine in adults aged ≥60 years. J Infect Dis 213:1872–1875. https://doi.org/10.1093/infdis/jiw047
Tseng HF, Bruxvoort K, Ackerson B et al (2020) The epidemiology of Herpes Zoster in immunocompetent, unvaccinated adults ≥50 years old: incidence, complications, hospitalization, mortality, and recurrence. J Infect Dis 222:798–806. https://doi.org/10.1093/infdis/jiz652
Tsujino H, Kondo E, Fukuoka T et al (2000) Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: a novel neuronal marker of nerve injury. Mol Cell Neurosci 15:170–182. https://doi.org/10.1006/mcne.1999.0814
Tyring S, Barbarash RA, Nahlik JE et al (1995) Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med 123:89–96. https://doi.org/10.7326/0003-4819-123-2-199507150-00002
Umorin M, Stinson C, Bellinger LL, Kramer PR (2016) Genes in the GABA pathway increase in the lateral thalamus of Sprague-Dawley rats during the proestrus/estrus phase. J Cell Physiol 231:1057–1064. https://doi.org/10.1002/jcp.25198
Vafai A, Wellish M, Gilden DH (1988) Expression of varicella-zoster virus in blood mononuclear cells of patients with postherpetic neuralgia. Proc Natl Acad Sci U S A 85:2767–2770. https://doi.org/10.1073/pnas.85.8.2767
Varela FH, Pinto LA, Scotta MC (2019) Global impact of varicella vaccination programs. Hum Vaccin Immunother 15:645–657. https://doi.org/10.1080/21645515.2018.1546525
Verweij MC, Wellish M, Whitmer T et al (2015) Varicella viruses inhibit interferon-stimulated JAK-STAT signaling through multiple mechanisms. PLoS Pathog 11:e1004901. https://doi.org/10.1371/journal.ppat.1004901
Visalli MA, House BL, Selariu A et al (2014) The varicella-zoster virus portal protein is essential for cleavage and packaging of viral DNA. J Virol 88:7973–7986. https://doi.org/10.1128/JVI.00376-14
Voss M, Paterson J, Kelsall IR et al (2011) Ppm1E is an in cellulo AMP-activated protein kinase phosphatase. Cell Signal 23:114–124. https://doi.org/10.1016/j.cellsig.2010.08.010
Wagner KM, McReynolds CB, Schmidt WK, Hammock BD (2017) Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases. Pharmacol Ther 180:62–76. https://doi.org/10.1016/j.pharmthera.2017.06.006
Wallace VCJ, Segerdahl AR, Lambert DM et al (2007) The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. Br J Pharmacol 151:1117–1128. https://doi.org/10.1038/sj.bjp.0707326
Warner BE, Yee MB, Zhang M et al (2021) Varicella-zoster virus early infection but not complete replication is required for the induction of chronic hypersensitivity in rat models of postherpetic neuralgia. PLOS Pathog 17:e1009689. https://doi.org/10.1371/journal.ppat.1009689
Watson PNC, Evans RJ, Watt VR, Birkett N (1988) Post-herpetic neuralgia: 208 cases. Pain 35:289–297. https://doi.org/10.1016/0304-3959(88)90139-X
Watson CPN, Deck JH, Morshead C et al (1991) Post-herpetic neuralgia: further post-mortem studies of cases with and without pain. Pain 44:105–117. https://doi.org/10.1016/0304-3959(91)90124-G
Webre JM, Hill JM, Nolan NM et al (2012) Rabbit and mouse models of HSV-1 latency, reactivation, and recurrent eye diseases. J Biomed Biotechnol 2012. https://doi.org/10.1155/2012/612316
Wei S, Li X, Wang H et al (2019) Analysis of the risk factors for postherpetic neuralgia. Dermatology 235:426–433. https://doi.org/10.1159/000500482
Wood KC, Blackwell JM, Geffen MN (2017) Cortical inhibitory interneurons control sensory processing. Curr Opin Neurobiol 46:200–207. https://doi.org/10.1016/j.conb.2017.08.018
Woodward M, Marko A, Galea S et al (2019) Varicella virus vaccine live: A 22-year review of postmarketing safety data. Open Forum Infect Dis 6:1–13. https://doi.org/10.1093/ofid/ofz295
Xiao X, Yang Y, Zhang Y et al (2013) Estrogen in the anterior cingulate cortex contributes to pain-related aversion. Cereb Cortex 23:2190–2203. https://doi.org/10.1093/cercor/bhs201
Xu X, Yang X, Zhang P et al (2012) Effects of exogenous galanin on neuropathic pain state and change of galanin and its receptors in DRG and SDH after sciatic nerve-pinch injury in rat. PLoS ONE 7:1–10. https://doi.org/10.1371/journal.pone.0037621
Yin X, Jing Y, Chen Q et al (2020) The intraperitoneal administration of MOTS-c produces antinociceptive and anti-inflammatory effects through the activation of AMPK pathway in the mouse formalin test. Eur J Pharmacol 870:172909. https://doi.org/10.1016/j.ejphar.2020.172909
Yokoyama H, Sasaki K, Franks ME et al (2009) Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin. Hum Gene Ther 20:63–71. https://doi.org/10.1089/hum.2008.094
Yokoyama H, Oguchi T, Goins WF et al (2013) Effects of herpes simplex virus vector-mediated enkephalin gene therapy on bladder overactivity and nociception. Hum Gene Ther 24:170–180. https://doi.org/10.1089/hum.2011.180
Yoshimura M, Yonehara N (2001) Influence of capsaicin cream in rats with peripheral neuropathy. Pharmacol Res 44:105–111. https://doi.org/10.1006/phrs.2001.0830
Yu L, Yang F, Luo H et al (2008) The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund’s adjuvant. Mol Pain 4:1744-8069-4–61. https://doi.org/10.1186/1744-8069-4-61
Yun H, Rowe AM, Lathrop KL et al (2014) Reversible nerve damage and corneal pathology in murine herpes simplex stromal keratitis. J Virol 88:7870–7880. https://doi.org/10.1128/jvi.01146-14
Yun H, Yee MB, Lathrop KL et al (2020) Production of the cytokine VEGF-A by CD4+ T and myeloid cells disrupts the corneal nerve landscape and promotes herpes stromal keratitis. Immunity 53:1050-1062.e5. https://doi.org/10.1016/j.immuni.2020.10.013
Zerboni L, Ku C-C, Jones CD et al (2005) Varicella-zoster virus infection of human dorsal root ganglia in vivo. Proc Natl Acad Sci 102:6490–6495. https://doi.org/10.1073/pnas.0501045102
Zerboni L, Sobel RA, Lai M et al (2012) 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 86:578–583. https://doi.org/10.1128/jvi.05950-11
Zerboni L, Sen N, Oliver SL, Arvin AM (2014) Molecular mechanisms of varicella zoster virus pathogenesis. Nat Rev Microbiol 12:197–210. https://doi.org/10.1038/nrmicro3215
Zhang Y, Lü N, Zhao Z-Q, Zhang Y-Q (2012) Involvement of estrogen in rapid pain modulation in the rat spinal cord. Neurochem Res 37:2697–2705. https://doi.org/10.1007/s11064-012-0859-1
Zou W, Huang C, Yang Y et al (2012) Microinjection of HSV-1 amplicon vector-mediated human proenkephalin into the periaqueductal grey attenuates neuropathic pain in rats. Int J Neurosci 122:189–194. https://doi.org/10.3109/00207454.2011.637653
Acknowledgements
The authors would like to acknowledge support by Public Health Service Awards from the National Institutes of Health (NIH) grants R01 NS064022, RO1 AI122640 (Kinchington), and R01 DE026749 (Kramer). BEW was supported by a T32 Award EY017272. The authors also acknowledge support by grants from Charles and Virginia Kaufmann Foundation, an NIH CORE grant P30 EY08098, and unrestricted support from the Eye and Ear Foundation of Pittsburgh and Research to Prevent Blindness Inc, New York, NY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Warner, B.E., Goins, W.F., Kramer, P.R., Kinchington, P.R. (2021). A Guide to Preclinical Models of Zoster-Associated Pain and Postherpetic Neuralgia. In: Arvin, A.M., Moffat, J.F., Abendroth, A., Oliver, S.L. (eds) Varicella-zoster Virus. Current Topics in Microbiology and Immunology, vol 438. Springer, Cham. https://doi.org/10.1007/82_2021_240
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