From the Department of Clinical Medicine (A.F., R.A., Y.Y.) the Department of Physiology (M.S., A.K., K.H., K.I.), Nihon University School of Dentistry, Tokyo, Japan.
Anesthesiology. 2018 Jun;128(6):1207-1219. doi: 10.1097/ALN.0000000000002139.
Patients with early stage tongue cancer do not frequently complain of tongue pain. Endothelin-1 signaling is upregulated in the cancerous tongue at the early stage. We tested the hypothesis that endothelin-1 signaling contributes to the modulation of tongue nociception.
Squamous cell carcinoma cells were inoculated into the tongue under general anesthesia. Lingual mechanical sensitivity under light anesthesia using forceps from days 1 to 21 (n = 8) and the amounts of endothelin-1 and β-endorphin in the tongue on days 6, 14, and 21 (n = 5 to 7) were examined after the inoculation. The effect of endothelin-A or µ-opioid receptor antagonism on the mechanical sensitivity was examined (n = 5 to 7).
Lingual mechanical sensitivity did not change at the early stage (days 5 to 6) but increased at the late stage (days 13 to 14). The amount of endothelin-1 increased (25.4 ± 4.8 pg/ml vs. 15.0 ± 5.2 pg/ml; P = 0.008), and endothelin-A receptor antagonism in the tongue induced mechanical hypersensitivity at the early stage (51 ± 9 g vs. 81 ± 6 g; P = 0.0001). The µ-opioid receptor antagonism enhanced mechanical hypersensitivity (39 ± 7 g vs. 81 ± 6 g; P < 0.0001), and the amount of β-endorphin increased at the early stage.
β-Endorphin released from the cancer cells via endothelin-1 signaling is involved in analgesic action in mechanical hypersensitivity at the early stage.
早期舌癌患者通常不会主诉舌痛。在早期癌变的舌组织中，内皮素-1 信号通路呈上调表达。我们验证了内皮素-1 信号通路参与舌痛觉调制的假说。
在全麻下将鳞状细胞癌接种于舌组织内。术后第 1 天至第 21 天，于浅麻醉下用镊子夹舌以检测舌机械感觉敏化程度（n = 8）；术后第 6、14、21 天，检测舌组织中内皮素-1 和β-内啡肽的含量（n = 5-7）。检测内皮素-A 或μ-阿片受体拮抗剂对机械敏感性的影响（n = 5-7）。
舌机械感觉敏化在早期（第 5-6 天）无明显改变，但在晚期（第 13-14 天）显著增加。舌组织中内皮素-1 的含量增加（25.4±4.8 pg/ml 比 15.0±5.2 pg/ml；P = 0.008），且早期内皮素-A 受体拮抗剂可诱导机械性痛觉过敏（51±9 g 比 81±6 g；P = 0.0001）。μ-阿片受体拮抗剂增强了机械性痛觉过敏（39±7 g 比 81±6 g；P < 0.0001），且早期β-内啡肽含量增加。
通过内皮素-1 信号通路从癌细胞释放的β-内啡肽参与了早期机械性痛觉过敏的镇痛作用。
