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Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury

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Abstract

Neuropathic pain results from nerve injury and is one of the most refractory disorders. Recently, many studies reported that glial cell-derived neurotrophic factor (GDNF) exhibited potent analgesic effects, but the underlying mechanisms still remain unknown. In addition to the classical GDNF-GFRα1-Ret pathway, GDNF can bind to adhesion proteins such as E-cadherin and NCAM via GFRα1 in a Ret-independent way. In this study, we aimed to examine whether the adhesion protein nectin-1 and its downstream protein c-Src are involved in neuropathic pain. We found that nectin-1 was expressed in the superficial dorsal horn of the spinal cord and that it was increased after chronic constrictive injury (CCI). Intrathecal administration of nectin-1 siRNA attenuated neuropathic pain induced by CCI via interference of the expression of nectin-1. Furthermore, we found that GDNF can downregulate the phosphorylation level of nectin-1-associated c-Src without changing the expression level of nectin-1. In summary, these data suggest that nectin-1 is involved in neuropathic pain, and that GDNF exerts analgesic effects by directly or indirectly regulating nectin-1/c-Src signaling. These findings may lead to a new target for the treatment of neuropathic pain.

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Abbreviations

GDNF:

Glial cell-derived neurotrophic factor

CCI:

Chronic constrictive injury

PWL:

Paw withdrawal latency

AJs:

Adherens junctions

TJs:

Tight junctions

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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, 09KJD320008).

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Authors and Affiliations

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

    Yuan-Yuan Gao, Xiao-Ya Hong & Hong-Jun Wang

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

    Yuan-Yuan Gao, Xiao-Ya Hong & Hong-Jun Wang

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  1. Yuan-Yuan Gao
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Correspondence to Hong-Jun Wang.

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All experimental procedures were approved by the Animal Care and Committee of Xuzhou Medical College (Xuzhou, Jiangsu Province, China) and were conducted in accordance with the Declaration of the National Institutes of Health Guide for Care and Use of Laboratory Animals (Publication No. 80–23, revised 1996).

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The authors declare that they have no conflict of interest.

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Gao, YY., Hong, XY. & Wang, HJ. Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury. J Mol Neurosci 60, 258–266 (2016). https://doi.org/10.1007/s12031-016-0792-x

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  • DOI: https://doi.org/10.1007/s12031-016-0792-x

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