Related Experiment Video
Updated: Jun 17, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
[Expression of metabotropic glutamate receptor 5 in spinal cord of morphine tolerant rats]
Jin-Bian Liu1, Wei Jiang, Ai-Zhong Wang
1Department of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China.
Objective:
To investigate the expression of metabotropic glutamate receptor 5 (mGluRS) in spinal cord of morphine tolerant rats and understand the influence of mGluR5 antagonist MPEP upon the expression of mGluRS.
Methods:
Male Sprague-Dawley rats were randomly divided into four groups with 8 rats each:control group (NS), morphine group, morphine plus MPEP group and MPEP group. A morphine tolerance model of rat was established by repeated administration of 10 microg morphine intrathecally twice daily for 7 days. The effects of morphine co-administrated with MPEP upon the thermal pain threshold were examined by tail flick test. Tail flick latency (TFL) was measured at 30 min pre- and postdosing. MPE% (percentage of maximal possible effect) was calculated by the equation: MPE (%) = [(test response time-basal response time)/(cut-off time-basal response time)] x 100%. The rats were sacrificed and L4-5 spinal cord tissue was removed. The expression of mGluR5 in every group was examined by immunofluorescence and Western blot.
Results:
MPE% of morphine group decreased gradually after chronic administration of morphine intrathecally. There was no significant difference between morphine group and control group at Day 7 (P > 0.05). Morphine plus MPEP group had significant analgesic effect as compared with morphine group at Day 7 (P < 0.05). The expression of mGluR5 was up-regulated in the dorsal horn of spinal cord in morphine tolerant rats. The protein level of mGluRS in morphine plus MPEP group was lower than that in morphine group (P < 0.05), but higher than control group (P < 0.05).
Conclusion:
The mGluR5 antagonist MPEP can prevent the development of morphine tolerance. The expression of mGluR5 protein increases in the spinal cord of morphine tolerant rats. MPEP plays its role in morphine tolerance by partly inhibiting the expression of mGluRS.
Insights
Metabotropic glutamate receptor 5 (mGluR5) expression increases in morphine-tolerant rats. An mGluR5 antagonist, MPEP, prevents morphine tolerance by inhibiting mGluR5 expression in the spinal cord.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioid tolerance is a significant clinical challenge, limiting long-term pain management.
- Metabotropic glutamate receptor 5 (mGluR5) has been implicated in pain signaling and opioid-induced hyperalgesia.
Purpose of the Study:
- To investigate the expression of mGluR5 in the spinal cord of rats with morphine tolerance.
- To determine the effect of the mGluR5 antagonist MPEP on morphine tolerance and mGluR5 expression.
Main Methods:
- A rat model of morphine tolerance was established through repeated intrathecal morphine administration.
- The effects of MPEP on thermal pain threshold were assessed using the tail flick test.
- Spinal cord mGluR5 expression was quantified using immunofluorescence and Western blot.
Main Results:
- Chronic morphine administration led to decreased analgesic effect (tolerance) and increased mGluR5 expression in the spinal cord dorsal horn.
- Co-administration of MPEP with morphine significantly attenuated the development of tolerance.
- MPEP treatment reduced mGluR5 protein levels in morphine-tolerant rats.
Conclusions:
- The mGluR5 antagonist MPEP effectively prevents the development of morphine tolerance.
- Increased spinal mGluR5 expression is associated with morphine tolerance.
- MPEP exerts its anti-tolerance effects by partially inhibiting mGluR5 expression in the spinal cord.
More Related Videos
08:16Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
05:24In Vivo SiRNA Transfection and Gene Knockdown in Spinal Cord via Rapid Noninvasive Lumbar Intrathecal Injections in Mice
Published on: March 22, 2014
Related Concept Videos
Opioid Receptors: Overview
Analgesia and Pain Management