Sympathetic modulation of head and neck cancer pain

头颈癌疼痛的交感神经调节

• 批准号: 10657584
• 负责人: Nicole N Scheff
• 金额: $ 37.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-06 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657584
• 关键词: Address; Adrenergic Agents; Adrenergic Antagonists; Adrenergic Receptor; Adrenergic beta-Antagonists; Afferent Neurons; Aftercare; Animal Model; Anxiety; Behavior; Behavioral; Benign; Biological; Breast; Calcium; Cancer Patient; Catecholamines; Cell Proliferation; Cells; Chronic stress; Clinical; Clinical Trials; Combined Modality Therapy; Data; Disease Progression; Dose; Electrophysiology (science); Goals; Growth; Growth and Development function; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; In Vitro; Incidence; Inflammation; Injury; Long-Term Effects; Malignant Neoplasms; Measures; Mediating; Mediator; Mental Depression; Metastatic Neoplasm to Lymph Nodes; Microscopy; Mus; Nerve; Neurons; Neuropeptides; Nociception; Norepinephrine; Optics; Oral; Oral cavity; Pain; Pain management; Patient Outcomes Assessments; Patients; Peripheral; Peripheral Nerves; Phase; Physiological; Plasma; Pre-Clinical Model; Predisposition; Propranolol; Prostate; Psychological Impact; Psychological Stress; Psychosocial Stress; Quality of life; Receptor Signaling; Reporting; Resolution; Risk Factors; Signal Transduction; Social support; Stains; Stress; Survivors; Sympathectomy; Sympathetic Nervous System; Symptoms; Testing; Therapeutic; Tongue; Treatment Protocols; Treatment-Related Cancer; Trigeminal System; Visualization; Xenograft procedure; afferent nerve; antagonist; beta-adrenergic receptor; cancer cell; cancer diagnosis; cancer invasiveness; cancer pain; carcinogenesis; chemical carcinogen; chronic pain; drinking water; emotional experience; experience; gastrointestinal; head and neck cancer patient; improved outcome; in vivo; malignant mouth neoplasm; mouse model; nerve supply; neurotransmission; novel therapeutic intervention; oral lesion; orofacial; pain behavior; pain symptom; palliation; pre-clinical; prognostic; prognostic indicator; prospective; psychological symptom; psychosocial; receptor expression; receptor function; survivorship; tumor; tumor microenvironment; tumor progression; tumorigenesis

PROJECT SUMMARY The majority of patients with head and neck squamous cell carcinoma (HNSCC) present with severe pain and increased stress which exceeds the levels seen in other cancers. Due to a multitude of factors, including amplificition of standard therapies, HNSCC patients are now living longer with the effects of their cancer and its treatment. The presence of pretreatment pain has been identified as a prognostic indicator of poor survival. The prognostic and long-term effects of cancer stress are unknown. Preliminary data using preclinical mouse models support of the efficacy of beta-adrenergic antagonism using beta-blockers in the treatment of cancer- related pain and progression; we found a reduction in orofacial nociceptive behavior and tumor size in cancer- bearing mice treated with propranolol in their drinking water. In addition, cancer-secreted mediators increased the adrenergic receptor signaling in trigeminal tongue primary afferent neurons as measured by norepinephrine evoked calcium transients. The hypothesis of this proposal is that sympathetic nervous system exacerbates cancer pain and drives tumor progression via local adrenergic signaling in the cancer microenvironment. To test this hypothesis, we will explore the relationship between patient-reported pain, psychological symptom burden (i.e., anxiety, depression, social support), and circulating catecholamine levels in HNSCC patients prior to treatment and through survivorship. We seek to determine if low pre-treatment pain and psychological symptom burden will predeict better patient reported outcomes during survivorship. Using preclinical mouse models of oral cancer, we will investigate the impact of cancer-mediated sensitization on adrenergic signaling in trigeminal primary afferent neurons innervating the tongue in vitro as well as the functional impact of stress on cancer pain behavior and associated peripheral nerve plasticity in vivo. In order to improve outcomes in HNSCC survivors, there is an urgency to better understand the prevelance of pain and stress in HNSCC patients, as well as the underlying biological mechanisms.

项目总结 大多数头颈部鳞状细胞癌(HNSCC)患者表现出剧烈的疼痛和 增加的压力超过了其他癌症的水平。由于多种因素，包括 随着标准治疗的扩大，HNSCC患者现在因癌症和其他疾病的影响而活得更长。 治疗。预处理痛的存在已被认为是预后不良的指标。 癌症应激的预后和长期影响尚不清楚。使用临床前小鼠的初步数据 模型支持使用β-受体阻滞剂治疗癌症的β-肾上腺素能拮抗剂的有效性。 相关的疼痛和进展；我们发现癌症患者的口腔面部伤害性行为和肿瘤大小减少- 在他们的饮用水中给予心得安治疗的小鼠。此外，癌症分泌的介质增加了 去甲肾上腺素测定三叉神经舌初级传入神经元的肾上腺素能受体信号 引发了钙瞬变。这一建议的假设是交感神经系统会加剧 癌症疼痛并通过癌症微环境中的局部肾上腺素能信号推动肿瘤进展。至 检验这一假设，我们将探索患者报告的疼痛与心理症状之间的关系 HNSCC患者既往的负担(即焦虑、抑郁、社会支持)和循环儿茶酚胺水平 通过治疗和生存。我们试图确定低的治疗前疼痛和心理 症状负担将预示着患者在生存期间报告的更好的结果。使用临床前小鼠 口腔癌模型，我们将研究癌症介导的致敏作用对肾上腺素能信号的影响。 三叉神经舌初级传入神经元的体外研究及应激对其功能的影响 癌症疼痛行为和相关的周围神经在体内的可塑性。为了改善#年的成果 HNSCC幸存者们，当务之急是更好地了解HNSCC患者的痛苦和压力 患者，以及潜在的生物学机制。