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ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord

  • Authors:
    • Xiang Zhu
    • Jinqian Liu
    • Yongjing Gao
    • Su Cao
    • Shiren Shen
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China, Institute of Nautical Medicine, Nantong University, Nantong, Jiangsu 226001, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1257-1265
    |
    Published online on: March 17, 2015
       https://doi.org/10.3892/ijmm.2015.2143
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Abstract

Although adenosine triphosphate-sensitive potassium (KATP) channels have been proven to be involved in regulating postoperative pain, the underlying mechanism remains to be investigated. In this study, we aimed to determine the role of spinal KATP channels in the control of mechanical hypersensitivity in a rat pain model, in which rats were subjected to skin/muscle incision and retraction (SMIR) surgery, as well as in LPS-stimulated astrocytes. The results showed that KATP channel subunits Kir6.1, SUR1 and SUR2 were normally expressed in the spinal cord and significantly downregulated after SMIR. SMIR caused a marked increase in monocyte chemoattractant protein-1 (MCP-1) mRNA expression and in the protein level of p-JNK in the spinal cord. Intrathecal administration of a KATP channel opener pinacidil (Pina) suppressed mechanical allodynia after SMIR and significantly downregulated the MCP-1 mRNA expression and the protein level of p-JNK induced by SMIR. Inverted fluorescence microscopy showed that Kir6.1 was co-localized with astrocytes only and SUR2 was co-localized primarily with neurons, in a small amount with astrocytes. Furthermore, in vitro studies showed that following incubation with LPS, the astrocytic MCP-1 mRNA expression and p-JNK content were markedly increased, whereas the mRNA levels of Kir6.1 and SUR2 were significantly downregulated in astrocytes. KATP channel opener pinacidil inhibited the LPS-triggered MCP-1 and p-JNK elevation in rat primary astrocytes. The results suggested that KATP channel opener treatment is an effective therapy for postoperative pain in animals, through the activation of the JNK/MCP-1 pathway in astrocytes.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu X, Liu J, Gao Y, Cao S and Shen S: ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord. Int J Mol Med 35: 1257-1265, 2015.
APA
Zhu, X., Liu, J., Gao, Y., Cao, S., & Shen, S. (2015). ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord. International Journal of Molecular Medicine, 35, 1257-1265. https://doi.org/10.3892/ijmm.2015.2143
MLA
Zhu, X., Liu, J., Gao, Y., Cao, S., Shen, S."ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord". International Journal of Molecular Medicine 35.5 (2015): 1257-1265.
Chicago
Zhu, X., Liu, J., Gao, Y., Cao, S., Shen, S."ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord". International Journal of Molecular Medicine 35, no. 5 (2015): 1257-1265. https://doi.org/10.3892/ijmm.2015.2143
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu X, Liu J, Gao Y, Cao S and Shen S: ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord. Int J Mol Med 35: 1257-1265, 2015.
APA
Zhu, X., Liu, J., Gao, Y., Cao, S., & Shen, S. (2015). ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord. International Journal of Molecular Medicine, 35, 1257-1265. https://doi.org/10.3892/ijmm.2015.2143
MLA
Zhu, X., Liu, J., Gao, Y., Cao, S., Shen, S."ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord". International Journal of Molecular Medicine 35.5 (2015): 1257-1265.
Chicago
Zhu, X., Liu, J., Gao, Y., Cao, S., Shen, S."ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord". International Journal of Molecular Medicine 35, no. 5 (2015): 1257-1265. https://doi.org/10.3892/ijmm.2015.2143
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