pISSN 2005-9159
eISSN 2093-0569

Experimental Research Article

Korean J Pain 2023; 36(4): 441-449

Published online October 1, 2023 https://doi.org/10.3344/kjp.23162

Copyright © The Korean Pain Society.

Involvement of the spinal γ-aminobutyric acid receptor in the analgesic effects of intrathecally injected hypertonic saline in spinal nerve-ligated rats

Myong-Hwan Karm1 , Hyun-Jung Kwon2 , Euiyong Shin2 , Honggyoon Bae3 , Young Ki Kim3 , Seong-Soo Choi2

1Department of Dental Anesthesiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea, 2Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, 3Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea

Correspondence to:Seong-Soo Choi
Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Tel: +82-2-3010-1538, Fax: +82-2-3010-6790, E-mail: choiss@amc.seoul.kr

*These authors contributed equally to this work.
Part of this study was presented at the University of Ulsan College of Medicine as M-H Karm's Ph.D. thesis (2019).

Handling Editor: Sang Hun Kim

Received: June 2, 2023; Revised: July 26, 2023; Accepted: August 5, 2023

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Hypertonic saline is used for treating chronic pain; however, clinical studies that aid in optimizing therapeutic protocols are lacking. We aimed to determine the concentration of intrathecally injected hypertonic saline at which the effect reaches its peak as well as the underlying γ-aminobutyric acid (GABA) receptor-related antinociceptive mechanism.
Methods: Spinal nerve ligation (SNL; left L5 and L6) was performed to induce neuropathic pain in rats weighing 250–300 g. Experiment 1: one week after implanting the intrathecal catheter, 60 rats were assigned randomly to intrathecal injection with 0.45%, 0.9%, 2.5%, 5%, 10%, and 20% NaCl, followed by behavioral testing at baseline and after 30 minutes, 2 hours, 1 day, and 1 week to determine the minimal concentration which produced maximal analgesia. Experiment 2: after determining the optimal intrathecal hypertonic saline concentration, 60 rats were randomly divided into four groups: Sham, hypertonic saline without pretreatment, and hypertonic saline after pretreatment with one of two GABA receptor antagonists (GABAA [bicuculline], or GABAB [phaclofen]). Behavioral tests were performed at weeks 1 and 3 following each treatment.
Results: Hypertonic saline at concentrations greater than 5% alleviated SNL-induced mechanical allodynia and had a significant therapeutic effect, while showing a partial time- and dose-dependent antinociceptive effect on thermal and cold hyperalgesia. However, pretreatment with GABA receptor antagonists inhibited the antinociceptive effect of 5% NaCl.
Conclusions: This study indicates that the optimal concentration of hypertonic saline for controlling mechanical allodynia in neuropathic pain is 5%, and that its analgesic effect is related to GABAA and GABAB receptors.

Keywords: Analgesia, Bicuculline, GABA Antagonists, Hyperalgesia, Hypertonic Saline, Neuralgia, Phaclofen, Receptors, GABA, Injections, Spinal.