The Korean Journal of Pain

  • 제36권4호
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  • Pages.441-449
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  • 2023
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  • 2005-9159(pISSN)
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  • 2093-0569(eISSN)
대한통증학회 (The Korean Pain Society)
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Involvement of the spinal γ-aminobutyric acid receptor in the analgesic effects of intrathecally injected hypertonic saline in spinal nerve-ligated rats

  • Myong-Hwan Karm (Department of Dental Anesthesiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Hyun-Jung Kwon (Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Euiyong Shin (Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Honggyoon Bae (Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine) ;
  • Young Ki Kim (Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine) ;
  • Seong-Soo Choi (Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine)
  • 투고 : 2023.06.02
  • 심사 : 2023.08.05
  • 발행 : 2023.10.01
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초록

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.

키워드

과제정보

The authors wish to express their gratitude to the Dental Research Institute of Seoul National University for providing an English language review of the manuscript.

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