title: Efficacy of Herpes Simplex Virus Vector Encoding the Human Preproenkephalin Gene for Treatment of Facial Pain in Mice.
abstract: OBJECTIVE
  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 replication-conditional 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 × 10(4) 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.forename: William E
authors.initials: WE
authors.lastname: Yoder
authors.forename: Karin N
authors.initials: KN
authors.lastname: Westlund
authors.forename: Charles R
authors.initials: CR
authors.lastname: Carlson
authors.forename: Craig S
authors.initials: CS
authors.lastname: Miller
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Danaher
mesh_terms: D000287:Administration, Topical; D000818:Animals; D059350:Chronic Pain / Q000628:therapy; D004195:Disease Models, Animal; D004745:Enkephalins / Q000235:genetics*; D005157:Facial Pain / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011498:Protein Precursors / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics*; D014110:Touch / Q000502:physiology; D014161:Transduction, Genetic / Q000379:methods; D014162:Transfection / Q000379:methods; D019076:Transgenes / Q000235:genetics; D012668:Trigeminal Ganglion / Q000821:virology; D014277:Trigeminal Neuralgia / Q000628:therapy
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; C033660:preproenkephalin
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