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.
|Number of pages||9|
|Journal||Journal of Oral and Facial Pain and Headache|
|State||Published - 2016|
Bibliographical noteFunding 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.
© 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