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Article

Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2

  • Authors:
    • Mei‑Li Zhai
    • Yi Chen
    • Chong Liu
    • Jian‑Bo Wang
    • Yong‑Hao Yu
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Tianjin Center Obstetrics and Gynecology Hospital, Central Obstetrics and Gynecology Hospital of Nankai University, Tianjin 300100, P.R. China, Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China, Department of Anesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin 300140, P.R. China
  • Pages: 1074-1080
    |
    Published online on: May 23, 2018
       https://doi.org/10.3892/mmr.2018.9057
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Abstract

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine. In the first experiment, the experimental rats were randomly divided into four groups: Control, morphine, morphine+GR antagonist mifepristone (RU38486) and morphine+GR agonist dexamethasone (Dex). Each group was treated with continuous intrathecal (IT) injection of the drugs for 6 days. The expression of GRs and MAPK 3/1 (p‑ERK 1/2) in the spinal dorsal horn was detected by western blot analysis and immunofluorescence staining. In the second experiment, the MAPK inhibitor PD98059 was added and the rats were randomly divided into four groups: Control, morphine, PD98059+morphine and PD98059+morphine+Dex. The continuous IT injection lasted for 7 days in each group. For all experiments, the tail flick test was conducted 30 min following administration every day to assess the thermal hyperalgesia of the rats. The experimental results demonstrated that there was a co‑existence of GRs and p‑ERK 1/2 in the spinal cord dorsal horn by double immunofluorescence staining. The GR antagonist RU38486 attenuated the morphine analgesia tolerance by inhibiting the expression of GR and increasing the expression of p‑ERK. The MAPK inhibitor PD98059 increased the effect of morphine tolerance and prolonged the duration of morphine tolerance. The present results suggest that spinal GRs may serve an important role in the development of morphine tolerance through the ERK signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Zhai ML, Chen Y, Liu C, Wang JB and Yu YH: Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2. Mol Med Rep 18: 1074-1080, 2018.
APA
Zhai, M., Chen, Y., Liu, C., Wang, J., & Yu, Y. (2018). Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2. Molecular Medicine Reports, 18, 1074-1080. https://doi.org/10.3892/mmr.2018.9057
MLA
Zhai, M., Chen, Y., Liu, C., Wang, J., Yu, Y."Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2". Molecular Medicine Reports 18.1 (2018): 1074-1080.
Chicago
Zhai, M., Chen, Y., Liu, C., Wang, J., Yu, Y."Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2". Molecular Medicine Reports 18, no. 1 (2018): 1074-1080. https://doi.org/10.3892/mmr.2018.9057
Copy and paste a formatted citation
x
Spandidos Publications style
Zhai ML, Chen Y, Liu C, Wang JB and Yu YH: Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2. Mol Med Rep 18: 1074-1080, 2018.
APA
Zhai, M., Chen, Y., Liu, C., Wang, J., & Yu, Y. (2018). Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2. Molecular Medicine Reports, 18, 1074-1080. https://doi.org/10.3892/mmr.2018.9057
MLA
Zhai, M., Chen, Y., Liu, C., Wang, J., Yu, Y."Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2". Molecular Medicine Reports 18.1 (2018): 1074-1080.
Chicago
Zhai, M., Chen, Y., Liu, C., Wang, J., Yu, Y."Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2". Molecular Medicine Reports 18, no. 1 (2018): 1074-1080. https://doi.org/10.3892/mmr.2018.9057
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