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Glial Cell-Derived Neurotrophic Factor Attenuates Neuropathic Pain in a Mouse Model of Chronic Constriction Injury: Possible Involvement of E-cadherin/p120ctn Signaling

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Abstract

Treating neuropathic pain is a major clinical challenge, and several key molecules associated with nociception have been suggested as potential targets for novel analgesics. Many studies have reported the anti-nociceptive effects of glial cell-derived neurotrophic factor (GDNF), but the underlying mechanism remains largely unknown. The present study was performed to assess the effects of GDNF in a mouse model of chronic constriction injury (CCI)-induced neuropathic pain. We also determined the potential role of E-cadherin/p120 catenin (p120ctn) signaling in these effects. Mice received an intrathecal acute injection of PBS, GDNF, and DECMA-1 (an E-cadherin functional blocking antibody) or a combination of DECMA-1 with GDNF on the testing days. Our results demonstrated that CCI caused a rapid decrease in E-cadherin and membrane-associated p120ctn in the spinal dorsal horn. Together, these data demonstrated that E-cadherin-associated p120ctn was upregulated by GDNF and that this upregulation was inhibited by pre-treatment with DECMA-1. Moreover, DECMA-1 significantly inhibited the effect of GDNF on thermal hyperalgesia. These data suggest that GDNF might have a therapeutic potential for the treatment of CCI-induced neuropathic pain and that the E-cadherin/p120ctn might play a role in GDNF-induced attenuation of thermal hyperalgesia.

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Acknowledgments

The study was supported by grants from National Nature Science Foundation of China (30901402、30900417) and the Educational Department Science Research Foundation of Jiangsu Province (08KJB180011 and 09KJD320008).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China

    Cunjin Wang, Hongjun Wang, Jun Pang, Li Li, Suming Zhang, Ge Song, Na Li, Junping Cao & Licai Zhang

  2. Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China

    Cunjin Wang, Hongjun Wang, Jun Pang, Li Li, Suming Zhang, Ge Song, Na Li, Junping Cao & Licai Zhang

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  1. Cunjin Wang
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  2. Hongjun Wang
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  3. Jun Pang
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  4. Li Li
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  5. Suming Zhang
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  7. Na Li
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Correspondence to Hongjun Wang.

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Cunjin Wang, Hongjun Wang, and Jun Pang contributed equally to this work.

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Wang, C., Wang, H., Pang, J. et al. Glial Cell-Derived Neurotrophic Factor Attenuates Neuropathic Pain in a Mouse Model of Chronic Constriction Injury: Possible Involvement of E-cadherin/p120ctn Signaling. J Mol Neurosci 54, 156–163 (2014). https://doi.org/10.1007/s12031-014-0266-y

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