Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, 807 Kaohsiung, Taiwan.
Department of Anesthesiology, Kaohsiung Medical University Hospital, 807 Kaohsiung, Taiwan.
Int J Mol Sci. 2019 Apr 20;20(8):1951. doi: 10.3390/ijms20081951.
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.
高压氧治疗（HBOT）已被用于减轻神经性疼痛。褪黑素和阿片受体参与神经性疼痛，但尚不清楚 HBOT 是否通过这些途径发挥作用以达到其镇痛作用。我们将麻醉大鼠分为两组治疗组和三组假手术组。两组治疗组均在右后爪上造成三度烧伤，一组在高压舱中治疗一周，另一组治疗两周。我们通过免疫组织化学、免疫荧光测定和实时定量聚合酶链反应（RT-PCR）评估机械性足底撤回阈值（MWT）以及中脑楔束核、背角和足底皮肤中褪黑素受体 1（MT1）、褪黑素受体 2（MT2）、μ（MOR）和 κ（KOR）阿片受体、脑源性神经营养因子（BDNF）、P 物质和降钙素基因相关肽（CGRP）的表达。接受一周 HBOT 治疗的大鼠表达 MT1、MT2、MOR 和 KOR 增加，BDNF、P 物质和 CGRP 表达减少。它们的机械疼痛水平在一周内恢复正常并持续三周。接受两周 HBOT 治疗的大鼠，这种抗痛觉过敏作用持续时间延长了两倍。我们的研究结果表明，延长 HBOT 的持续时间可以在大鼠中减轻烧伤引起的机械性痛觉过敏，并持续较长时间。HBOT 一周后观察到的褪黑素和阿片受体的上调表明它们可能部分参与了机械性痛觉过敏的减轻。BDNF、P 物质和 CGRP 的下调也可能对 HBOT 的整体有益作用有贡献。
