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Spinal N-Cadherin/CREB Signaling Contributes to Chronic Alcohol Consumption-Enhanced Postsurgical Pain

Authors Ma Y, Zhang X, Li C, Liu S, Xing Y, Tao F

Received 15 June 2020

Accepted for publication 31 July 2020

Published 12 August 2020 Volume 2020:13 Pages 2065—2072

DOI https://doi.org/10.2147/JPR.S267778

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Robert B. Raffa


Yajing Ma,1,2 Xinye Zhang,1 Changsheng Li,3 Sufang Liu,1,2 Ying Xing,1 Feng Tao2

1Department of Physiology and Neurobiology, Zhengzhou University School of Basic Medical Sciences, Zhengzhou, Henan, People’s Republic of China; 2Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, Texas, USA; 3Department of Anesthesiology, Zhengzhou University School of Medicine, Zhengzhou, People’s Republic of China

Correspondence: Ying Xing
Department of Physiology and Neurobiology, Zhengzhou University School of Basic Medical Sciences, 100 Ke Xue Ave, Zhengzhou, Henan 450001, People’s Republic of China
Tel +86-371-67780665
Email xingy@zzu.edu.cn
Feng Tao
Department of Biomedical Sciences, Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX 75246, USA
Tel +1-214-828-8272
Email ftao81@tamu.edu

Background: It has been reported that N-cadherin and cAMP response element binding protein (CREB) in the spinal cord are critical for synaptogenesis and regulation of excitatory synapse function, which could underlie chronic pain development. The aim of the present study was to investigate the role of spinal N-cadherin/CREB signaling in postsurgical pain chronicity following chronic alcohol consumption.
Methods: C57BL/6 male mice were randomly assigned into different groups. Plantar incision was used to induce postsurgical pain. Chronic alcohol consumption was conducted by giving mice unlimited access to different concentrations of ethanol for five weeks. We measured paw withdrawal thresholds to test postsurgical pain. Using Western blotting, we examined the expression of N-Cadherin and CREB in the spinal dorsal horn. We further performed intrathecal injection of specific N-cadherin and CREB inhibitors to assess the role of spinal N-cadherin/CREB signaling in chronic alcohol consumption-enhanced postsurgical pain.
Results: We observed that the chronic alcohol consumption significantly prolonged postsurgical pain and enhanced plantar incision-increased N-cadherin expression and CREB phosphorylation at the Ser133 in the spinal cord. Intrathecal injection of specific N-cadherin and CREB inhibitors attenuated chronic alcohol consumption-prolonged postsurgical pain.
Conclusion: Our results suggest that spinal N-cadherin/CREB signaling is involved in chronic alcohol consumption-caused postsurgical pain chronicity.

Keywords: incisional pain, spinal cord, intrathecal injection, ethanol

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