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
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
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DOI：
10.1002/art.22635
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发表时间：
2007-06-01
影响因子：
--
通讯作者：
Tallents, Ross H.
中科院分区：
文献类型：
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作者：
Kyrkanides, Stephanos;Fiorentino, Paolo M.;Tallents, Ross H.
目标。目的：探讨阿片受体的功能，为关节炎抗感觉性治疗提供基础。我们使用猫免疫缺陷病毒（FM）载体，在小鼠关节炎关节中诱导人类mu-阿片受体（幽默）的表达，这种病毒能够稳定地转导分裂、生长受阻和终末分化的细胞。研究了在C57BL/6J基因背景下培养的雄性和雌性Col1-IL-1 β (XAT)转基因小鼠和野生型仔鼠。在诱导关节炎前1周，在Col1-IL-1 β (XAT)转基因小鼠的颞下颌关节单次注射FIV(HuMOR)，可防止口面部疼痛和关节功能障碍的发展，并降低关节的组织病理学异常程度。此外，FIV（幽默）阻止了三叉神经感觉神经元的致敏和脑干三叉神经感觉核星形胶质细胞的激活。这些作用是通过FIV载体从周围神经末梢转运到感觉神经节介导的初级感觉神经元的转导，这一点在位于三叉神经节的神经元细胞体以及位于脑干主感觉和尾侧核的近端和远端神经分支和关节中的表达得到了证明。MOR配体主要存在于三叉神经降核，表明观察到的抗感觉发生在尾侧亚核。关节软骨细胞和半月板组织也被FIV（幽默）感染，推测FIV对软骨有抗炎作用。我们的研究结果表明，关节中MOR过表达的预防性治疗可以成功地预防关节炎关节疼痛、功能障碍和组织病理学异常的发展。这些发现可能为未来发展时空控制的抗关节炎和抗炎治疗提供基础。
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 (FM vector, which is capable of stably transducing dividing, growth-arrested, and terminally differentiated cells. Male and female Col1-IL-1 beta(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-1 beta(XAT)- transgenic mice I 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 sulnucleus 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.