TY - JOUR
T1 - Amelioration of pain and histopathologic joint abnormalities in the Col1-IL-1βXAT mouse model of arthritis by intraarticular induction of μ-opioid receptor into the temporomandibular joint
AU - Kyrkanides, Stephanos
AU - Fiorentino, Paolo M.
AU - Miller, Jen Nie H.
AU - Gan, Yanjun
AU - Lai, Yu Ching
AU - Shaftel, Solomon S.
AU - Puzas, J. Edward
AU - Piancino, Maria G.
AU - O'Banion, M. Kerry
AU - Tallents, Ross H.
PY - 2007/6
Y1 - 2007/6
N2 - Objective. To evaluate opioid receptor function as a basis for novel antinociceptive therapy in arthritis. Methods. We induced human μ-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-1βXAT-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-1βXAT- 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. Conclusion. 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.
AB - Objective. To evaluate opioid receptor function as a basis for novel antinociceptive therapy in arthritis. Methods. We induced human μ-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-1βXAT-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-1βXAT- 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. Conclusion. 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.
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U2 - 10.1002/art.22635
DO - 10.1002/art.22635
M3 - Article
C2 - 17530644
AN - SCOPUS:34447526546
SN - 0004-3591
VL - 56
SP - 2038
EP - 2048
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 6
ER -