A Novel Syngeneic Immunocompetent Mouse Model of Head and Neck Cancer Pain Independent of Interleukin-1 Signaling.
A Novel Syngeneic Immunocompetent Mouse Model of Head and Neck Cancer Pain Independent of Interleukin-1 Signaling.
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DOI：
10.1213/ane.0000000000005302
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发表时间：
2021-04-01
影响因子：
5.7
通讯作者：
Laumet G
中科院分区：
文献类型：
--
作者：
Heussner MJ;Folger JK;Dias C;Massri N;Dahdah A;Vermeer PD;Laumet G
疼痛是头颈部癌症患者最先出现的症状之一，随着疾病的进展，他们经常会出现慢性和使人衰弱的疼痛。疼痛也是一个重要的生存预后指标。不幸的是，由于我们对头颈癌疼痛（HNCP）的机制了解有限，患者很少接受有效的疼痛治疗。疼痛通常与神经炎症，特别是IL-1信号传导有关。本研究的目的是在免疫活性小鼠中建立一种新的HNCP同基因模型，以检查IL-1信号转导的贡献。在雄性C57 BL/6小鼠的右后肢中注射人乳头瘤病毒（HPV+）诱导的口咽鳞状细胞癌的鼠模型以诱导肿瘤生长。通过von Frey细丝测量疼痛敏感性。自发性疼痛通过面部鬼脸量表进行评估。通过qPCR和ELISA定量基因表达来测量白细胞介素（IL）-1β。疼痛超敏反应和自发性疼痛在肿瘤细胞植入后迅速发展，此时肿瘤体积仍然微不足道。在荷瘤小鼠中，脊髓和循环IL-1β水平显著升高。通过鞘内注射IL-1受体拮抗剂（IL-1 ra）或基因缺失（Il 1 r1 −/−）阻断IL-1信号传导并不能缓解HNCP。我们在免疫活性小鼠中建立了第一个HNCP同基因模型。与炎症或神经损伤疼痛不同，HNCP不依赖于IL-1信号传导。这些发现挑战了头颈癌患者疼痛是由组织压迫或IL-1信号引起的普遍看法。
Pain is one of the first presenting symptoms in patients with head and neck cancer, who often develop chronic and debilitating pain as the disease progresses. Pain is also an important prognostic marker for survival. Unfortunately, patients rarely receive effective pain treatment due to our limited knowledge of the mechanisms underlying head and neck cancer pain (HNCP). Pain is often associated with neuroinflammation and particularly IL-1 signaling. The purpose of this study is to develop a novel syngeneic model of HNCP in immunocompetent mice in order to examine the contribution of IL-1 signaling. Male C57BL/6 mice were injected with a murine model of human papillomavirus (HPV+) induced oropharyngeal squamous cell carcinoma in their right hindlimb in order to induce tumor growth. Pain sensitivity was measured via von Frey filaments. Spontaneous pain was assessed via the facial grimace scale. Interleukin (IL)-1β was measured by quantifying gene expression via qPCR and ELISA. Pain hypersensitivity and spontaneous pain develop quickly after the implantation of tumor cells, a time when tumor volume is still insignificant. Spinal and circulating IL-1β levels are significantly elevated in tumor-bearing mice. Blocking IL-1 signaling either by intrathecal administration of IL-1 receptor antagonist (IL-1ra) or by genetic deletion (Il1r1−/−) does not alleviate HNCP. We established the first syngeneic model of HNCP in immunocompetent mice. Unlike inflammatory or nerve injured pain, HNCP is independent of IL-1 signaling. These findings challenge the common belief that pain results from tissue compression or IL-1 signaling in patients with head and neck cancer.