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Activation of CXCL10/CXCR3 Signaling Attenuates Morphine Analgesia: Involvement of Gi Protein

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Abstract

Morphine is a potent agonist of μ-opioid receptor and is widely used to relieve severe pain, including cancer pain. Some chemokines, for example, CX3CL1 and CCL2, participate in the regulation of opioid santinociception. In our previous study, we found overexpression of chemokine CXCL10/CXCR3 in spinal cord participated in the development of cancer-induced bone pain, so we supposed that CXCL10 may have influence in morphine analgesia in cancer pain relief. In this study, we found that a single dose of morphine could transiently increase the expression of CXCL10 in spinal cord. Blocking the function of CXCL10 enhanced morphine antinociception in cancer-induced bone pain rats. However, overexpression of CXCL10 induced acute algesia and decreased the analgesic effect of morphine in normal mice. The algesic effect of CXCL10 was blocked by inhibition of CXCR3 and Gi protein. These results suggested that CXCL10 in spinal cord serves as a novel negative regulator of morphine analgesia and provided evidence that activation of CXCL10/CXCR3 in spinal cord may attenuate antinociceptive potency of morphine in cancer pain relief.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of the People's Republic of China (No. 81171259, No. 81371250, and No. 81070890) and also supported by 2010 Clinical Key Disciplines Construction Grant from the Ministry of Health of China.

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Authors and Affiliations

  1. Department of Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Dawei Ye

  2. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Huilian Bu, Genhua Guo, Bin Shu, Wei Wang, Xuehai Guan, Hui Yang, Xuebi Tian, Hongbing Xiang & Feng Gao

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  1. Dawei Ye
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  2. Huilian Bu
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  3. Genhua Guo
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  5. Wei Wang
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  10. Feng Gao
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Correspondence to Feng Gao.

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Dawei Ye and Huilian Bu contributed equally to this work.

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Ye, D., Bu, H., Guo, G. et al. Activation of CXCL10/CXCR3 Signaling Attenuates Morphine Analgesia: Involvement of Gi Protein. J Mol Neurosci 53, 571–579 (2014). https://doi.org/10.1007/s12031-013-0223-1

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  • DOI: https://doi.org/10.1007/s12031-013-0223-1

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