背景:口腔癌是最痛苦的癌症类型之一,并且通常是现有镇痛药的难治性。口腔癌患者经常对阿片类药物产生耐受性,目前癌症疼痛治疗的支柱,给他们留下了有限的治疗选择。因此,为了开发新的镇痛药,非常需要确定驱动口腔癌疼痛的分子机制。以前的报道表明,口腔癌患者会经历剧烈的机械性疼痛和功能疼痛。迄今为止,没有研究检查口腔癌患者的热痛或饮酒在口腔癌疼痛中的作用。这项研究旨在评估患者报告的疼痛水平和热异常性疼痛,介导热异常性疼痛的潜在分子机制,以及饮酒对患者感觉到的疼痛的影响。
方法:这项研究评估了人口腔鳞状细胞癌(OSCC)细胞系在体外激活热敏通道的能力,并在大鼠口面部疼痛模型中验证了这些发现。使用视觉模拟量表(VAS)检查了德克萨斯州南部OSCC队列(n=27)中患者报告的疼痛。协变分析检查了烟草和酒精消费等变量,种族,性别,和癌症阶段。
结果:我们确定OSCC分泌的因子在体外刺激瞬时受体电位Ankyrin1型通道(TRPA1;有害冷传感器)和瞬时受体电位Vanilloid1型通道(TRPV1;有害热传感器),并且OSCC分泌的因子在体内使TRPV1伤害感受器敏感。这些发现在这个队列中得到了验证,据报道,对冷和热的异常性疼痛。值得注意的是,报告定期饮酒的受试者也报告了每种类型的疼痛测试的疼痛评分较低,显著减少寒冷引起的疼痛,疼痛,燃烧的疼痛。
结论:口腔癌患者会经历多种类型的癌症疼痛,包括热异常性疼痛。饮酒与减少OSCC疼痛和减少热异常性疼痛相关,这可能是由TRPA1和TRPV1介导的。因此,这些患者疼痛减轻可能会导致延迟寻求治疗,因此延迟了早期检测和治疗。
BACKGROUND: Oral cancer is one of the most painful cancer types, and is often refractory to existing analgesics. Oral cancer patients frequently develop a tolerance to opioids, the mainstay of current cancer pain therapy, leaving them with limited therapeutic options. Thus, there is a great need to identify molecular mechanisms driving oral cancer pain in an effort to develop new analgesics. Previous reports demonstrate that oral cancer patients experience intense mechanical pain and pain in function. To date, no studies have examined thermal pain in oral cancer patients or the role that alcohol consumption plays in oral cancer pain. This study aims to evaluate patient-reported pain levels and thermal allodynia, potential molecular mechanisms mediating thermal allodynia, and the effects of alcohol consumption on patient-perceived pain.
METHODS: This study evaluated human oral squamous cell carcinoma (OSCC) cell lines for their ability to activate thermosensitive channels in vitro and validated these findings in a rat model of orofacial pain. Patient-reported pain in a south Texas OSCC cohort (n = 27) was examined using a visual analog scale (VAS). Covariant analysis examined variables such as tobacco and alcohol consumption, ethnicity, gender, and cancer stage.
RESULTS: We determined that OSCC secretes factors that stimulate both the Transient Receptor Potential Ankyrin type 1 channel (TRPA1; noxious cold sensor) and the Transient Receptor Potential Vanilloid type 1 channel (TRPV1; noxious heat sensor) in vitro and that OSCC-secreted factors sensitize TRPV1 nociceptors in vivo. These findings were validated in this cohort, in which allodynia to cold and heat were reported. Notably, subjects that reported regular alcohol consumption also reported lower pain scores for every type of pain tested, with significantly reduced cold-induced pain, aching pain, and burning pain.
CONCLUSIONS: Oral cancer patients experience multiple types of cancer pain, including thermal allodynia. Alcohol consumption correlates with reduced OSCC pain and reduced thermal allodynia, which may be mediated by TRPA1 and TRPV1. Hence, reduced pain in these patients may contribute to a delay in seeking care, and thus a delay in early detection and treatment.