癌症患者经常经历心理健康的变化，这促使人们探索浸润肿瘤的神经是否通过影响大脑功能而导致这些变化。我们使用头颈癌雄性小鼠模型，利用神经元追踪技术，结果表明肿瘤浸润神经确实通过同侧三叉神经节连接到不同的大脑区域。这种神经元回路的激活导致行为改变，表现为筑巢减少、吃饼干的延迟增加以及车轮运行减少。钙动员增加表明肿瘤浸润的伤害感受神经元活性增强。相应地，与非肿瘤小鼠相比，接受这些神经投射的特定大脑区域显示出荷瘤小鼠的 cFos 和 delta FosB 表达升高，同时钙反应也明显增强。荷瘤小鼠中伤害感受器神经元的基因消除导致大脑 Fos 表达减少，并减轻了肿瘤存在引起的行为改变。虽然镇痛治疗成功地使荷瘤小鼠的口腔运动行为恢复正常，但它对随意跑轮却没有类似的治疗效果。这种差异表明了一种错综复杂的关系，其中疼痛并不是这种行为转变的唯一驱动因素。阐明肿瘤、浸润神经和大脑之间的相互作用对于制定有针对性的干预措施以减轻与癌症相关的心理健康负担至关重要。

Cancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a male mouse model for head and neck cancer, we utilized neuronal tracing techniques and show that tumor-infiltrating nerves indeed connect to distinct brain areas via the ipsilateral trigeminal ganglion. The activation of this neuronal circuitry led to behavioral alterations represented by decreased nest-building, increased latency to eat a cookie, and reduced wheel running. Tumor-infiltrating nociceptor neurons exhibited heightened activity, as indicated by increased calcium mobilization. Correspondingly, the specific brain regions receiving these neural projections showed elevated cFos and delta FosB expression in tumor-bearing mice, alongside markedly intensified calcium responses compared to non-tumor-bearing counterparts. The genetic elimination of nociceptor neurons in tumor-bearing mice led to decreased brain Fos expression and mitigated the behavioral alterations induced by the presence of the tumor. While antalgic treatment successfully restored behaviors involving oral movements to normalcy in tumor-bearing mice, it did not have a similar therapeutic effect on voluntary wheel running. This discrepancy points towards an intricate relationship, where pain is not the exclusive driver of such behavioral shifts. Unraveling the interaction between the tumor, infiltrating nerves, and the brain is pivotal to developing targeted interventions to alleviate the mental health burdens associated with cancer.