Abstract
The underlying mechanisms of opioid-induced hyperalgesia (OIH) remain unclear. Herein, we found that the protein expression of metabotropic glutamate receptor 1 (mGluR1) was significantly increased in the right but not in the left laterocapsular division of central nucleus of the amygdala (CeLC) in OIH rats. In CeLC neurons, the frequency and the amplitude of mini-excitatory postsynaptic currents (mEPSCs) were significantly increased in fentanyl group which were decreased by acute application of a mGluR1 antagonist, A841720. Finally, the behavioral hypersensitivity could be reversed by A841720 microinjection into the right CeLC. These results show that the right CeLC mGluR1 is an important factor associated with OIH that enhances synaptic transmission and could be a potential drug target to alleviate fentanyl-induced hyperalgesia.
Graphical Abstract
Data availability
The authors acknowledge that the data presented in this study must be deposited and made publicly available in an acceptable repository, prior to publication.
Abbreviations
- OIH:
-
Opioid-induced hyperalgesia
- mGluR:
-
Metabotropic glutamate receptor
- CeLC:
-
Laterocapsular division of central nucleus of the amygdala
- mEPSCs:
-
Mini-excitatory postsynaptic currents
- ERK:
-
Extracellular signal-regulated kinase (ERK)
- NMDA:
-
N-Methyl-d-aspartate
- iGluR:
-
Ionotropic glutamate receptor
- ACSF:
-
Artificial cerebrospinal fluid
- RVM:
-
Rostroventral medulla of the brainstem
- LA/BLA:
-
Lateral/basolateral amygdala nuclei
- ITC:
-
Intercalated cell mass of the amygdala
- CeA:
-
Central nucleus of the amygdala
- mPFC:
-
Medial prefrontal cortex
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This work was supported by the National Natural Science Foundation of China (grant nos. 31870771, 31500996, 3212018, 81271234, 81771196), National Science Foundation of Hubei (2020CFA025), the Fundamental Research Funds for the Central Universities, South-Central MinZu University (CZY17030, CZY18027, CZY19023, CZQ20004), and Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment (PJS140011610).
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CL, HC, and TB designed the study; HC, TB, WH, and JL implemented the experiments; HC, XL, SC, FL, and XY analyzed data; TB, HC, and CL drafted the paper. TB and HC contributed equally to this work.
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Bai, T., Chen, H., Hu, W. et al. Amygdala Metabotropic Glutamate Receptor 1 Influences Synaptic Transmission to Participate in Fentanyl-Induced Hyperalgesia in Rats. Cell Mol Neurobiol 43, 1401–1412 (2023). https://doi.org/10.1007/s10571-022-01248-x
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DOI: https://doi.org/10.1007/s10571-022-01248-x