title: Amelioration of pain and histopathologic joint abnormalities in the Col1-IL-1beta(XAT) mouse model of arthritis by intraarticular induction of mu-opioid receptor into the temporomandibular joint.
abstract: OBJECTIVE
  To evaluate opioid receptor function as a basis for novel antinociceptive therapy in arthritis.
  
  
  METHODS
  We induced human mu-opioid receptor (HuMOR) expression in arthritic joints of mice, using the feline immunodeficiency virus (FIV) vector, which is capable of stably transducing dividing, growth-arrested, and terminally differentiated cells. Male and female Col1-IL-1beta(XAT)-transgenic mice developed on a C57BL/6J background and wild-type littermates were studied.
  
  
  RESULTS
  A single injection of FIV(HuMOR) into the temporomandibular joints of Col1-IL-1beta(XAT)-transgenic mice 1 week prior to induction of arthritis prevented the development of orofacial pain and joint dysfunction, and reduced the degree of histopathologic abnormality in the joint. In addition, FIV(HuMOR) prevented the attendant sensitization of trigeminal sensory neurons and activation of astroglia in brainstem trigeminal sensory nuclei. These effects were mediated by the transduction of primary sensory neurons via transport of FIV vectors from peripheral nerve endings to sensory ganglia, as evidenced by HuMOR expression in neuronal cell bodies located in the trigeminal ganglia, as well as in their proximal and distal nerve branches located in the main sensory and subnucleus caudalis of the brainstem and joints, respectively. The presence of MOR ligands predominantly in the descending trigeminal nucleus suggested that the observed antinociception occurred at the subnucleus caudalis. Articular chondrocytes and meniscal tissue were also infected by FIV(HuMOR), which presumably exerted an antiinflammatory effect on cartilage.
  
  
  CONCLUSIONS
  Our results indicate that prophylactic therapy with MOR overexpression in joints can successfully prevent the development of pain, dysfunction, and histopathologic abnormalities in the joints in arthritis. These findings may provide a basis for the future development of spatiotemporally controlled antinociceptive and antiinflammatory therapy for arthritis.
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. stephanos_kyrkanides@urmc.rochester.edu
authors.forename: Stephanos
authors.initials: S
authors.lastname: Kyrkanides
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Fiorentino
authors.forename: Jen-nie H
authors.initials: JN
authors.lastname: Miller
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Gan
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lai
authors.forename: Solomon S
authors.initials: SS
authors.lastname: Shaftel
authors.forename: J Edward
authors.initials: JE
authors.lastname: Puzas
authors.forename: Maria G
authors.initials: MG
authors.lastname: Piancino
authors.forename: M Kerry
authors.initials: MK
authors.lastname: O'Banion
authors.forename: Ross H
authors.initials: RH
authors.lastname: Tallents
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016089:Immunodeficiency Virus, Feline; D007270:Injections, Intra-Articular; D053583:Interleukin-1beta / Q000235:genetics / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009475:Neurons, Afferent / Q000502:physiology; D010003:Osteoarthritis / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D013704:Temporomandibular Joint / Q000378:metabolism / Q000503:physiopathology; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D014161:Transduction, Genetic; D014278:Trigeminal Nuclei / Q000473:pathology / Q000503:physiopathology
chemical_list: D053583:Interleukin-1beta; D010446:Peptide Fragments; D017450:Receptors, Opioid, mu; C471083:Col-1 peptide, human; D020778:Matrix Metalloproteinase 2