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Dose-Dependent Effect of Hyperbaric Oxygen Treatment on Burn-Induced Neuropathic Pain in Rats

1
Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
3
Department of Anesthesiology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 807, Taiwan
4
Department of Anesthesiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5
Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
6
Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7
Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan
8
Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
9
Department of Plastic & Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 807, Taiwan
10
School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
11
Departments of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(8), 1951; https://doi.org/10.3390/ijms20081951
Received: 1 March 2019 / Revised: 12 April 2019 / Accepted: 18 April 2019 / Published: 20 April 2019
(This article belongs to the Special Issue Neuroprotective Strategies 2019)
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Abstract

Hyperbaric oxygen treatment (HBOT) has been used to reduce neuropathic pain. Melatonin and opioid receptors are involved in neuropathic pain, but it is not known if HBOT works through these pathways to achieve its antinociceptive effect. We divided anesthetized rats into two treatment and three sham groups. The two treatment groups received third-degree burns on their right hind paws, one treated in a hyperbaric chamber for a week and the other for two weeks. We evaluated the mechanical paw-withdrawal threshold (MWT) and expression of melatonin receptor 1 (MT1), melatonin receptor 2 (MT2), μ (MOR) and κ (KOR) opioid receptor, brain-derived neurotrophic factor (BDNF), Substance P, and calcitonin gene-related peptide (CGRP) in cuneate nucleus, dorsal horn, and hind paw skin by immunohistochemical, immunofluorescence assays and real-time quantitative polymerase chain reaction (RT-PCR). The group receiving one-week HBOT had increased expressions of MT1, MT2, MOR and KOR and decreased expressions of BDNF, Substance P, and CGRP. Their mechanically measured pain levels returned to normal within a week and lasted three weeks. This anti-allodynia effect lasted twice as long in those treated for two weeks. Our findings suggest that increasing the duration of HBOT can reduce burn-induced mechanical allodynia for an extended period of time in rats. The upregulation of melatonin and opioid receptors observed after one week of HBOT suggests they may be partly involved in attenuation of the mechanical allodynia. Downregulation of BDNF, substance P and CGRP may have also contributed to the overall beneficial effect of HBOT. View Full-Text
Keywords: melatonin; opioid receptor; neuropathic pain; hyperbaric oxygen; cuneate nucleus melatonin; opioid receptor; neuropathic pain; hyperbaric oxygen; cuneate nucleus
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Wu, Z.-S.; Wu, S.-H.; Lee, S.-S.; Lin, C.-H.; Chang, C.-H.; Lo, J.-J.; Chai, C.-Y.; Wu, C.-S.; Huang, S.-H. Dose-Dependent Effect of Hyperbaric Oxygen Treatment on Burn-Induced Neuropathic Pain in Rats. Int. J. Mol. Sci. 2019, 20, 1951.

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