title: Attenuation of myogenic orofacial nociception and mechanical hypersensitivity by viral mediated enkephalin overproduction in male and female rats.
abstract: BACKGROUND
  Clinical studies have tested the use of an engineered herpes virus to treat pain. We hypothesized that subcutaneous injections of an engineered herpes virus that expresses enkephalin would attenuate orofacial nociception and hypersensitivity in male and female rats by a central mechanism.
  
  
  METHODS
  Herpes virus was injected subcutaneously around the mouth of male and female rats seventy-two hours before ligatures were placed on the masseter tendon, control treatment groups received either no virus or no ligature. Enkephalin expression was measured and von Frey filament testing and meal duration were utilized to measure mechanical hypersensitivity and the nociceptive response, respectively. Naloxone or naloxone methiodide was administered to rats injected with the enkephalin expressing virus to test if enkephalin was acting peripherally or centrally.
  
  
  RESULTS
  Ligature significantly lengthened meal duration and reduced the threshold to von Frey filaments for 18 days. Infection with the enkephalin transgene significantly decreased this response for at least 11 days but only in male rats. Virus injection significantly increased expression of enkephalin in the mental nerve that innervates the mouth region, the trigeminal ganglia and the trigeminal nucleus caudalis but no increase was observed in the masseter nerve after virus injection. Naloxone but not naloxone methiodide reversed the response to the enkephaline expressing virus.
  
  
  CONCLUSIONS
  The data suggests that sex should be a considered when using this virus and that viral transfection of the mental nerve with an enkephalin transgene can reduce nociception and hypersensitivity through a central mechanism.
authors.affiliation: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX, 75246, USA. pkramer@bcd.tamhsc.edu.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Kramer
authors.affiliation: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX, 75246, USA. umorin@bcd.tamhsc.edu.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Umorin
authors.affiliation: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX, 75246, USA. lbellinger@bcd.tamhsc.edu.
authors.forename: Larry L
authors.initials: LL
authors.lastname: Bellinger
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004745:Enkephalins / Q000378:metabolism*; D005260:Female; D006564:Herpesviridae / Q000378:metabolism*; D006566:Herpesviridae Infections; D006930:Hyperalgesia; D008297:Male; D008406:Masseter Muscle / Q000601:surgery*; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000378:metabolism; D014278:Trigeminal Nuclei / Q000378:metabolism*
chemical_list: D004745:Enkephalins; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D009270:Naloxone; C041269:N-methylnaloxone