Department of Oral Physiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka Suita-shi, Osaka 565-0871, Japan; Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka Suita-shi, Osaka 565-0871, Japan.
Department of Oral Physiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka Suita-shi, Osaka 565-0871, Japan.
Neuroscience. 2022 Feb 10;483:66-81. doi: 10.1016/j.neuroscience.2021.12.002. Epub 2021 Dec 6.
Obstructive sleep apnea (OSA), characterized by low arterial oxygen saturation during sleep, is associated with an increased risk of orofacial pain. In this study, we simulated chronic intermittent hypoxia (CIH) during the sleep/rest phase (light phase) to determine the role of transient receptor potential vanilloid 1 (TRPV1) in mediating enhanced orofacial nocifensive behavior and trigeminal spinal subnucleus caudalis (Vc) neuronal responses to capsaicin (a TRPV1 agonist) stimulation in a rat model of OSA. Rats were subjected to CIH (nadir O, 5%) during the light phase for 8 or 16 consecutive days. CIH yielded enhanced behavioral responses to capsaicin after application to the ocular surface and intraoral mucosa, which was reversed under normoxic conditions. The percentage of TRPV1-immunoreactive trigeminal ganglion neurons was greater in CIH rats than in normoxic rats and recovered under normoxic conditions after CIH. The ratio of large-sized TRPV1-immunoreactive trigeminal ganglion neurons increased in CIH rats. The density of TRPV1 positive primary afferent terminals in the superficial laminae of Vc was higher in CIH rats. Phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive cells intermingled with the central terminal of TRPV1-positive afferents in the Vc. The number of pERK-immunoreactive cells following low-dose capsaicin (0.33 µM) application to the tongue was significantly greater in the middle portion of the Vc of CIH rats than of normoxic rats and recovered under normoxic conditions after CIH. These data suggest that CIH during the sleep (light) phase is sufficient to transiently enhance pain on the ocular surface and intraoral mucosa via TRPV1-dependent mechanisms.
阻塞性睡眠呼吸暂停（OSA）的特征是睡眠期间动脉血氧饱和度降低，与口面疼痛风险增加有关。在这项研究中，我们在睡眠/休息阶段（光照阶段）模拟慢性间歇性低氧（CIH），以确定瞬时受体电位香草酸 1（TRPV1）在介导增强的口面伤害性行为和三叉神经脊核尾侧亚核（Vc）神经元对辣椒素（TRPV1 激动剂）刺激的反应中的作用，在 OSA 大鼠模型中。大鼠在光照阶段连续 8 或 16 天接受 CIH（最低 O2，5%）。CIH 导致应用于眼表面和口腔粘膜后对辣椒素的行为反应增强，在正常氧条件下逆转。CIH 大鼠三叉神经节中 TRPV1 免疫反应性神经元的百分比大于正常氧大鼠，在 CIH 后在正常氧条件下恢复。CIH 大鼠中 TRPV1 免疫反应性大型三叉神经节神经元的比例增加。Vc 浅层中 TRPV1 阳性初级传入末梢的密度在 CIH 大鼠中较高。磷酸化细胞外信号调节激酶（pERK）-免疫反应性细胞与 TRPV1 阳性传入纤维的中枢末端交织在 Vc 中。CIH 大鼠 Vc 中部接受低剂量辣椒素（0.33µM）应用于舌后，pERK-免疫反应性细胞的数量明显大于正常氧大鼠，在 CIH 后在正常氧条件下恢复。这些数据表明，睡眠（光照）阶段的 CIH 足以通过 TRPV1 依赖性机制暂时增强眼表面和口腔粘膜的疼痛。
