IMR Press / JIN / Volume 21 / Issue 4 / DOI: 10.31083/j.jin2104121
Open Access Original Research
Endogenous Cannabinoid Receptors Modulate Plasticity at Immature Synapses
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1 Department of Anesthesiology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, 430000 Wuhan, Hubei, China
*Correspondence: (Jiang Wu)
Academic Editor: Rafael Franco
J. Integr. Neurosci. 2022, 21(4), 121;
Submitted: 23 November 2021 | Revised: 1 March 2022 | Accepted: 10 March 2022 | Published: 28 June 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: To explore the mechanism of endocannabinoid cannabinoid receptor 1 (CB1) receptor pathway that regulates synaptic plasticity in the dorsal horn of the spinal cord of rats with neuropathic pain at different ages. Methods: Neonatal, juvenile, and adult male sprague dawley (SD) rats were divided into the spinal nerve preservation injury (SNI), SNI + Anandamide (AEA), SNI + D-AP5, SNI + CNQX, SNI + D-AP5 + AEA, SNI + CNQX + AEA, sham SNI, sham SNI + AEA, sham SNI + D-AP5, sham SNI + CNQX, sham SNI + D-AP5 + AEA, and sham SNI + CNQX + AEA groups, respectively. Paw withdrawal threshold (PWT) and long-term potentiation (LTP) of the spinal dorsal horn PS (field potential) were assessed to judge the spinal cord’s functional state. Immunohistochemical staining and Western blot were conducted to detect CB1 protein levels in the spinal dorsal horn. Results: The LTP response in the spinal cord was alleviated in the SNI + AEA group. After treatment with the N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, the LTP of neonatal A nerve was relieved further. After treatment with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker CNQX, LTP change in the A nerve was not obvious. The LTP of the A and C nerves were relieved after D-AP5 or CNQX treatment in young and adult animals; however, the blocking effect of CNQX was obvious. The altered levels of PWT and CB1 support these results. Conclusions: The CB1 receptor activation produces analgesia in neonatal rats through NMDA receptor formation for PS inhibitory activity. In juvenile and adult rats, this phenomenon was effectuated through NMDA and AMPA receptors. This difference could be attributed to the varied number of NMDA and/or AMPA receptors activated during development and changes in the NMDA/AMPA receptor ratio.

cannabinoid signaling pathway
NMDA receptor
AMPA receptor
neonatal rat
juvenile rat
Fig. 1.
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