Open Access

Melatonin regulation of transcription in the reversal of morphine tolerance: Microarray analysis of differential gene expression

  • Authors:
    • Yu‑Che Cheng
    • Ru‑Yin Tsai
    • Yen‑Tseng Sung
    • Ing‑Jung Chen
    • Tzu‑Yi Tu
    • Ya‑Yuan Mao
    • Chih‑Shung Wong
  • View Affiliations

  • Published online on: December 18, 2018     https://doi.org/10.3892/ijmm.2018.4030
  • Pages: 791-806
  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tolerance and associated hyperalgesia induced by long‑term morphine administration substantially restrict the clinical use of morphine in pain treatment. Melatonin, a neurohormone released by the pineal gland, has been demonstrated to attenuate anti‑nociceptive morphine tolerance. The present study investigates differentially expressed genes in the process of morphine tolerance and altered gene expression subsequent to melatonin treatment in chronic morphine‑infused ratspinal cords. Morphine tolerance was induced in male Wistar rats by intrathecal morphine infusion (the MO group). Melatonin (the MOMa group) was administered to overcome the effects derived by morphine. The mRNA collected from L5‑S3 of the spinal cord was extracted and analysed by rat expression microarray. Principal component analysis and clustering analysis revealed that the overall gene profiles were different in morphine and melatonin treatments. Subsequent to Gene Ontology analysis, the biological processes of differentially expressed genes of MO and MOMa compared with the control group were constructed. Furthermore, a panel of genes exclusively expressed following melatonin treatment and another panel of genes with inverse expression between the MO and MOMa group were also established. Subsequent to PANTHER pathway analysis, a group of genes with inverse expression following melatonin administrated compared with morphine alone were identified. The expression levels of genes of interest were also confirmed using a reverse transcription‑quantitative polymerase chain reaction. The gene panel that was constructed suggests a potential signaling pathway in morphine tolerance development and is valuable for investigating the mechanism of morphine tolerance and the regulatory gene profiles of melatonin treatment. These results may contribute to the discovery of potential drug targets in morphine tolerance treatments in the future.
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February-2019
Volume 43 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Cheng YC, Tsai RY, Sung YT, Chen IJ, Tu TY, Mao YY and Wong CS: Melatonin regulation of transcription in the reversal of morphine tolerance: Microarray analysis of differential gene expression . Int J Mol Med 43: 791-806, 2019
APA
Cheng, Y., Tsai, R., Sung, Y., Chen, I., Tu, T., Mao, Y., & Wong, C. (2019). Melatonin regulation of transcription in the reversal of morphine tolerance: Microarray analysis of differential gene expression . International Journal of Molecular Medicine, 43, 791-806. https://doi.org/10.3892/ijmm.2018.4030
MLA
Cheng, Y., Tsai, R., Sung, Y., Chen, I., Tu, T., Mao, Y., Wong, C."Melatonin regulation of transcription in the reversal of morphine tolerance: Microarray analysis of differential gene expression ". International Journal of Molecular Medicine 43.2 (2019): 791-806.
Chicago
Cheng, Y., Tsai, R., Sung, Y., Chen, I., Tu, T., Mao, Y., Wong, C."Melatonin regulation of transcription in the reversal of morphine tolerance: Microarray analysis of differential gene expression ". International Journal of Molecular Medicine 43, no. 2 (2019): 791-806. https://doi.org/10.3892/ijmm.2018.4030