Anesthesiology and Intensive Care Medicine, International University of Health and Welfare, 852 Hatakeda, Narita City, Chiba, 286-0124, Japan.
Peace of Mind Co., Ltd, 2-8-6 Tokuo, Kita-Ku, Kumamoto City, Kumamoto, 861-5525, Japan.
Cell Mol Neurobiol. 2023 Nov;43(8):4345-4362. doi: 10.1007/s10571-023-01430-9. Epub 2023 Nov 7.
Neuromodulation through magnetic fields irradiation with ait® (AT-04), a device that irradiates a mixed alternating magnetic fields (2 kHz and 83.3 MHz), has been shown to have high efficacy for fibromyalgia and low back pain in our previous clinical trials. The aim of this study was to elucidate the underlying analgesic mechanism of the AT-04 using the partial sciatic nerve ligation (PSL) model as an animal model of neuropathic pain. AT-04 was applied to PSL model rats with hyperalgesia and its pain-improving effect was verified by examining mechanical allodynia using the von Frey method. The results demonstrated a significant improvement in hyperalgesia in PSL model rats. We also examined the involvement of descending pain modulatory systems in the analgesic effects of AT-04 using antagonism by serotonin and noradrenergic receptor antagonists. These antagonists significantly reduced the analgesic effect of AT-04 on pain in PSL model rats by approximately 50%. We also measured the amount of serotonin and noradrenaline in the spinal fluid of PSL model rats using microdialysis during AT-04 treatment. Both monoamines were significantly increased by magnetic fields irradiation with AT-04. Furthermore, we evaluated the involvement of opioid analgesia in the analgesic effects of AT-04 using naloxone, the main antagonist of the opioid receptor, and found that it significantly antagonized the effects by approximately 60%. Therefore, the analgesic effects of AT-04 in PSL model rats involve both the endogenous pain modulation systems, including the descending pain modulatory system and the opioid analgesic system.
磁场刺激疗法通过磁场辐射(ait®,辐射混合交替磁场,2 kHz 和 83.3 MHz)已被证明对纤维肌痛和腰痛具有高疗效,这是我们之前临床试验的结果。本研究旨在通过坐骨神经部分结扎(PSL)模型作为神经病理性疼痛的动物模型,阐明 AT-04 的潜在镇痛机制。将 AT-04 应用于痛觉过敏的 PSL 模型大鼠,通过 Von Frey 方法检查机械性痛觉过敏来验证其改善疼痛的效果。结果表明,PSL 模型大鼠的痛觉过敏得到了显著改善。我们还使用 5-羟色胺和去甲肾上腺素能受体拮抗剂的拮抗作用,研究了下行疼痛调节系统在 AT-04 镇痛作用中的参与情况。这些拮抗剂使 AT-04 对 PSL 模型大鼠疼痛的镇痛作用降低了约 50%。我们还通过微透析测量了 AT-04 治疗期间 PSL 模型大鼠脊髓液中 5-羟色胺和去甲肾上腺素的含量。两种单胺类物质均因 AT-04 的磁场辐射而显著增加。此外,我们使用阿片受体的主要拮抗剂纳洛酮评估了 AT-04 镇痛作用中阿片类镇痛药的参与情况,发现它使镇痛作用显著拮抗了约 60%。因此,AT-04 在 PSL 模型大鼠中的镇痛作用涉及内源性疼痛调节系统,包括下行疼痛调节系统和阿片类镇痛系统。
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