Journal of Pain Research (Aug 2020)
Spinal N-Cadherin/CREB Signaling Contributes to Chronic Alcohol Consumption-Enhanced Postsurgical Pain
Abstract
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 ChinaCorrespondence: Ying XingDepartment of Physiology and Neurobiology, Zhengzhou University School of Basic Medical Sciences, 100 Ke Xue Ave, Zhengzhou, Henan 450001, People’s Republic of ChinaTel +86-371-67780665Email [email protected] TaoDepartment of Biomedical Sciences, Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX 75246, USATel +1-214-828-8272Email [email protected]: 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
