Efficacy of herpes simplex virus vector encoding the human preproenkephalin gene for treatment of facial pain in mice

Fei Ma, Chunmei Wang, William E. Yoder, Karin N. Westlund, Charles R. Carlson, Craig S. Miller, Robert J. Danaher

Research output: Contribution to journalArticlepeer-review

7 Citations (SciVal)


Aims: To determine whether herpes simplex virus-based vectors can efficiently transduce mouse trigeminal ganglion (TG) neurons and attenuate preexisting nerve injury-induced whisker pad mechanical hypersensitivity in a trigeminal inflammatory compression (TIC) neuropathic pain model. Methods: Tissue transduction efficiencies of replication-conditional and replication-defective vectors to mouse whisker pads after topical administration and subcutaneous injection were assessed using quantitative real-time PCR (qPCR). Tissue tropism and transgene expression were assessed using qPCR and reverse-transcriptase qPCR following topical application of the vectors. Whisker pad mechanical sensitivities of TIC-injured mice were determined using graduated von Frey fibers before and after application of human preproenkephalin expressing replicationconditional vector (KHPE). Data were analyzed using one-way analysis of variance (ANOVA) and post hoc tests. Results: Transduction of target TGs was 8- to 50- fold greater after topical application than subcutaneous injection and = 100-fold greater for replication-conditional than replication-defective vectors. Mean KHPE loads remained constant in TGs (4.5-9.8 × 104 copies/TG) over 3 weeks but were below quantifiable levels (10 copies/tissue) within 2 weeks of application in other nontarget cephalic tissues examined. Transgene expression in TGs was maximal during 2 weeks after topical application (100-200 cDNA copies/mL) and was below quantifiable levels (1 cDNA copy/mL) in all nontarget tissues. Topical KHPE administration reduced TIC-related mechanical hypersensitivity on whisker pads 4-fold (P < .05) for at least 1 week. Conclusion: Topically administered KHPE produced a significant antinociceptive effect in the TIC mouse model of chronic facial neuropathic pain. This is the first report in which a gene therapeutic approach reduced trigeminal pain-related behaviors in an established pain state in mice.

Original languageEnglish
Pages (from-to)42-50
Number of pages9
JournalJournal of Oral and Facial Pain and Headache
Issue number1
StatePublished - 2016

Bibliographical note

Funding Information:
The authors thank Hejab Malik, Michael Rechtin, and Dr Li Ping Zhang for their help in this research, and Matt Hazzard for creating the Fig 5 illustration. The investigation was supported by NIH COBRE grant 2P20RR020145-06 and from internal institutional sources from the University of Kentucky President's Research Professorship Fund (KNW) and the College of Medicine Dean's Start-up Fund (KNW). The authors report no conflicts of interest related to this study.

Publisher Copyright:
© 2016 by Quintessence Publishing Co Inc.


  • Gene therapy
  • Mechanical allodynia
  • Nerve injury
  • Neuropathic pain
  • Trigeminal ganglia

ASJC Scopus subject areas

  • Dentistry (miscellaneous)
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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