Kasai Satoka, Ukai Saki, Kuroda Junpei, Yamauchi Tsugumi, Yamada Daisuke, Saitoh Akiyoshi, Iriyama Satoshi, Suzuki Masashi, Arita Kazuki, Nakano Yoshio, Miyazaki Satoru, Yoshizawa Kazumi
Laboratory of Pharmacology and Therapeutics, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika-ku, Tokyo, Japan.
Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Katsushika-ku, Tokyo, Japan.
PLoS One. 2025 Jul 9;20(7):e0324730. doi: 10.1371/journal.pone.0324730. eCollection 2025.
Pain is a complex phenomenon encompassing both the physiological and psychological aspects of sensation and emotion, respectively. In recent years, pain has been clarified to arise even without direct injury, with emotional transmission as a cause. However, the specific mechanisms behind emotional transmission are still not well understood. In this study, sounds in the ultrasonic domain that were recorded during pain stimulation in mice were used as sound stress to examine the effects of psychological stress caused by exposure to ultrasound on tactile thresholds. We also examined the effects of psychological stress caused by the ultrasound on an inflammatory pain model of mice. The tactile threshold decreased the next and three days after sound stress exposure in mice. DNA microarray analysis of the mouse thalamus exposed to sound stress revealed increased expression of inflammation-related genes, Prostaglandin-endoperoxide synthase 2 and C-X-C motif chemokine ligand 1. Their respective inhibitors, loxoprofen and SB225002, significantly improved hyperalgesia induced by sound stress. When sound stress was applied to a mouse model of inflammatory pain in which pain thresholds were restored 14 days after complete Freund's adjuvant administration, prolonged pain and attenuated analgesic effects of loxoprofen were observed. These results suggest that sound stress not only induces inflammation in the brain that causes hyperalgesia but may also be partially responsible for exacerbating inflammatory pain, hence complicating treatment.
疼痛是一种复杂的现象，分别包含感觉和情绪的生理及心理方面。近年来，已明确即使没有直接损伤也会产生疼痛，其原因是情绪传递。然而，情绪传递背后的具体机制仍未得到充分理解。在本研究中，将小鼠疼痛刺激期间记录的超声领域声音用作声音应激，以研究暴露于超声引起的心理应激对触觉阈值的影响。我们还研究了超声引起的心理应激对小鼠炎症性疼痛模型的影响。在小鼠暴露于声音应激后的第二天和第三天，触觉阈值降低。对暴露于声音应激的小鼠丘脑进行DNA微阵列分析，结果显示炎症相关基因前列腺素内过氧化物合酶2和C-X-C基序趋化因子配体1的表达增加。它们各自的抑制剂洛索洛芬和SB225002显著改善了声音应激诱导的痛觉过敏。当将声音应激施加于完全弗氏佐剂给药14天后疼痛阈值恢复的炎症性疼痛小鼠模型时，观察到疼痛延长以及洛索洛芬的镇痛作用减弱。这些结果表明，声音应激不仅会在大脑中诱发导致痛觉过敏的炎症，还可能部分导致炎症性疼痛加剧，从而使治疗变得复杂。
