Effects of oxytocin on responses to nociceptive and non-nociceptive stimulation in the upper central nervous system.
Effects of oxytocin on responses to nociceptive and non-nociceptive stimulation in the upper central nervous system.
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催产素对上中枢神经系统伤害性和非伤害性刺激反应的影响。
DOI：
10.1016/j.bbrc.2021.08.042
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Masanori Yamauchi
中科院分区：
文献类型：
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作者：
Hidehisa Saito;Shizu Hidema;Ayano Otsuka;Jun Suzuki;Michio Kumagai;Akihiro Kanaya;Toru Murakami;Yusuke Takei;Kazutomo Saito;Shigekazu Sugino;Hiroaki Toyama;Ryuta Saito;Teiji Tominaga;Katsuhiko Nishimori;Masanori Yamauchi
催产素被称为一种社会联系激素，但它也具有抗焦虑或镇痛神经递质的作用。当催产素作为神经递质集中调节疼痛或焦虑时，它由神经元分泌并直接投射到目标区域。尽管催产素在脊髓水平的功能已得到充分研究，但其在脊髓上水平的作用却知之甚少。我们的目的是使用 C57BL/6J（野生型 [WT]）、催产素缺陷型 (Oxt−/−)、催产素受体缺陷型 (Oxtr−/−) 和催产素受体金星 (OxtrVenus/+) 小鼠品系研究催产素在体内脊髓上水平的影响。哈格里夫斯和哈格里夫斯的 Oxtr−/− 小鼠的反应阈值von-Frey 测试显着低于 WT 小鼠，而旷场和光/暗测试显示没有显着差异。此外，在施用催产素后，Oxt−/−小鼠的反应阈值提高至WT小鼠的响应阈值。哈格里夫斯试验后，我们观察到 OxtrVenus/+ 小鼠中导水管周围灰质 (PAG)、内侧杏仁核 (MeA) 和伏隔核 (NAc) 区域中 c-fos 与金星或催产素受体的共定位。此外，在 PAG、MeA 和 NAc 区域，Oxtr−/− 小鼠中催产素与 c-fos 和 γ-氨基丁酸的共定位比 WT 小鼠中强得多。然而，根据von-Frey测试，仅在MeA和NAc区域观察到相同的结果。我们的结果表明，催产素通过PAG区域对疼痛刺激发挥镇痛作用，并通过MeA和NAc区域对不愉快刺激发挥自我保护作用。
Oxytocin is known as a social bonding hormone, but it also functions as an anxiolytic or analgesic neurotransmitter. When oxytocin regulates pain or anxiousness centrally as a neurotransmitter, it is secreted by neurons and directly projected to targeted regions. Although the function of oxytocin at the spinal level is well studied, its effects at the supraspinal level are poorly understood. We aimed to investigate the effect of oxytocin at the supraspinal level in vivo using C57BL/6J (wild-type [WT]), oxytocin-deficient (Oxt−/−), oxytocin receptor-deficient (Oxtr−/−), and oxytocin receptor-Venus (OxtrVenus/+) mice lines.Response thresholds inOxtr−/−mice in Hargreaves and von-Frey tests were significantly lower than those in WT mice, whereas open field and light/dark tests showed no significant differences. Moreover, response thresholds inOxt−/−mice were raised to those in WT mice after oxytocin administration. Following the Hargreaves test, we observed the co-localisation of c-fos with Venus or the oxytocin receptor in the periaqueductal gray (PAG), medial amygdala (MeA), and nucleus accumbens (NAc) regions inOxtrVenus/+mice. Furthermore, in the PAG, MeA, and NAc regions, the co-localisation of oxytocin with c-fos and gamma-aminobutyric acid was much stronger inOxtr−/−mice than in WT mice. However, following von-Frey test, the same findings were observed only in the MeA and NAc regions.Our results suggest that oxytocin exerts its analgesic effect on painful stimulation via the PAG region and a self-protective effect on unpleasant stimulation via the MeA and NAc regions.