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Temporal and Spatial Changes of μ-Opioid Receptors in the Brain, Spinal Cord and Dorsal Root Ganglion in a Rat Lumbar Disc Herniation Model

Kaneuchi, Yoichi, MD, PhD; Sekiguchi, Miho, MD, PhD; Kameda, Takuya, MD, PhD; Kobayashi, Yoshihiro, MD, PhD; Konno, Shin-ichi, MD, PhD

doi: 10.1097/BRS.0000000000002776
BASIC SCIENCE
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SDC

Study Design. Controlled, interventional, animal study.

Objective. To investigate the spatial and temporal changes of μ-opioid receptor (MOR) expression in a rat lumbar disc herniation (LDH) model.

Summary of Background Data. MORs widely express in the peripheral and central nervous systems, and opioid drugs produce an analgesic effect through their activation. However, the efficacy of opioid drugs is sometimes inadequate in several pathological conditions of pain. MORs in the brain as well as the spinal cord (SC) and dorsal root ganglion (DRG) are thought to be associated with pain-related behavior, but the underlying mechanisms are not completely understood.

Methods. In all, 91 adult female Sprague-Dawley rats were used. Autologous nucleus pulposus (NP) was applied onto the left L5 DRG in the NP group rats. Rats were divided into two surgical groups, the NP and the sham group. The von Frey test of left hind paw was performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. Immunohistochemistry and immunoblotting in the DRG, SC, Caudate putamen, nucleus accumbens (NAc) and periaqueductal grey matter were performed before surgery, and 2, 7, 14, 21 and 28 days after surgery.

Results. The thresholds in the NP group were significantly lower than those in the sham group from day 2 onwards. At days 7 and 14, MOR expression in the injured-side SC and DRG were significantly lower than those in the sham group. At day 21, MOR in the NAc was significantly decreased compared to that in the sham group.

Conclusion. Changes of MOR expression in the NAc, SC and DRG were associated with pain-related behavior. This result might show the underling pathogenesis of the resistance to MOR agonists in the patient with LDH.

Level of Evidence: N/A

Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.

Address correspondence and reprint requests to Miho Sekiguchi, MD, PhD, Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295, Japan; E-mail: miho-s@fmu.ac.jp

Received 30 April, 2018

Revised 4 June, 2018

Accepted 6 June, 2018

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work.

No relevant financial activities outside the submitted work.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.