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Updated: May 18, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Regulation of mammalian MOR-1 gene expression after chronic treatment with morphine
Rose V Prenus1, Ebens Luscar, Zhi-Ping Zhu
1College of Pharmacy and Pharmaceutical Sciences, Florida A__AMB__M University, Tallahassee, FL 32307, USA.
Abstract:
Morphine is an effective analgesic that acts by binding to the µ-opioid receptor (MOR) coded in the human by the OPRM1 gene. In the present study, we investigated the regulation of µ-opioid receptor (MOR-1) mRNA levels in all-trans-retinoic acid-differentiated SH-SY5Y human neuroblastoma cells under in vitro conditions with 10 µM morphine treatment for 24 h. In addition, we measured the MOR-1 levels in recombinant Chinese hamster ovary (CHO) cells, transfected with human µ-opioid receptor gene (hMOR) with 10 µM morphine treatment for 24 h. The isolated mRNA from these cells was subjected to real-time quantitative RT-PCR analysis to determine the regulation of µ-opioid receptor gene expression. It was observed that morphine treatment did not alter MOR-1 levels in undifferentiated SH-SY5Y cells compared to undifferentiated control cells. However, the MOR-1 levels in all-trans-retinoic acid-differentiated cells were significantly higher compared to the undifferentiated cells. Morphine treatment in differentiated SH-SY5Y cells caused significant downregulation of MOR-1 expression compared to the control cells. In the morphine-treated CHO cells, the hMOR-1 mRNA levels remained the same as the untreated control. Finally, pretreatment of SH-SY5Y cells with 10 µM naloxone, the antagonist of µ-opioid receptor, for 1 h significantly blocked the downregulation of MOR-1 mRNA levels with morphine treatment. These findings suggest that regulation of MOR-1 gene expression is cell-type specific after chronic morphine treatment and provide some evidence in the understanding of morphine tolerance.
Insights
Morphine
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Morphine is a potent analgesic acting on the µ-opioid receptor (MOR), encoded by the OPRM1 gene.
- Understanding MOR regulation is crucial for pain management and opioid tolerance.
- SH-SY5Y neuroblastoma and CHO cells are used as in vitro models.
Purpose of the Study:
- To investigate the effect of morphine on µ-opioid receptor (MOR-1) mRNA levels in differentiated and undifferentiated SH-SY5Y cells.
- To examine MOR-1 mRNA regulation in morphine-treated Chinese hamster ovary (CHO) cells.
- To determine if naloxone can block morphine-induced downregulation of MOR-1.
Main Methods:
- Real-time quantitative RT-PCR was used to measure MOR-1 mRNA levels.
- SH-SY5Y cells were differentiated with all-trans-retinoic acid.
- Cells were treated with 10 µM morphine for 24 hours, with or without naloxone pretreatment.
Main Results:
- Morphine did not affect MOR-1 levels in undifferentiated SH-SY5Y cells.
- Differentiated SH-SY5Y cells showed higher MOR-1 levels than undifferentiated cells.
- Morphine significantly downregulated MOR-1 in differentiated SH-SY5Y cells but not in CHO cells.
- Naloxone pretreatment blocked morphine-induced MOR-1 downregulation in differentiated SH-SY5Y cells.
Conclusions:
- µ-opioid receptor (MOR-1) gene expression regulation is cell-type specific in response to morphine.
- Findings suggest a mechanism contributing to morphine tolerance.
- This study provides insights into the complex regulation of opioid receptors.
Related Concept Videos
Opioid Receptors: Overview
Analgesia and Pain Management
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Regulation of Expression at Multiple Steps
Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

