Sympathetic modulation of head and neck cancer pain

头颈癌疼痛的交感神经调节

• 批准号: 10274967
• 负责人: Nicole N Scheff
• 金额: $ 37.17万
• 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/10274967
• 关键词: Address; Adrenergic Agents; Adrenergic Antagonists; Adrenergic Receptor; Adrenergic beta-Antagonists; Afferent Neurons; 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 of activation protein; Mental Depression; Metastatic Neoplasm to Lymph Nodes; Microscopy; Mus; Nerve; Neurons; Neuropeptides; Nociception; Norepinephrine; Optics; Oral; Pain; Pain management; Patient Outcomes Assessments; Patients; Peripheral; Peripheral Nerves; Phase; Physiological; Plasma; Pre-Clinical Model; Prognostic Marker; Propranolol; Prostate; Psychological Impact; Psychological Stress; Psychosocial Stress; Quality of life; Receptor Signaling; Reporting; Resolution; Risk Factors; Sensory; Signal Transduction; Social support; Stains; Stress; Survivors; Sympathectomy; Sympathetic Nervous System; Symptoms; Testing; Therapeutic; Tongue; Treatment Protocols; Treatment-Related Cancer; Trigeminal System; Xenograft procedure; afferent nerve; beta-adrenergic receptor; cancer cell; cancer diagnosis; 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; orofacial; pain behavior; pain symptom; palliation; pre-clinical; prognostic; 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.

项目概要 大多数头颈鳞状细胞癌 (HNSCC) 患者会出现剧烈疼痛和 压力增加超过其他癌症的水平。由于多种因素，包括 随着标准疗法的扩大，HNSCC 患者现在由于癌症及其影响而活得更长。 治疗。治疗前疼痛的存在已被确定为生存不良的预后指标。 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 受体阻滞剂的 β 肾上腺素拮抗剂在癌症治疗中的功效 相关的疼痛和进展；我们发现癌症中口面部伤害性行为和肿瘤大小有所减少- 小鼠的饮用水中含有普萘洛尔。此外，癌症分泌的介质增加 通过去甲肾上腺素测量三叉神经舌初级传入神经元中的肾上腺素受体信号传导 诱发钙瞬变。该提案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信号传导驱动肿瘤进展。到 为了检验这个假设，我们将探讨患者报告的疼痛与心理症状之间的关系 HNSCC 患者的负担（即焦虑、抑郁、社会支持）和循环儿茶酚胺水平 到治疗并通过生存。我们试图确定治疗前的疼痛和心理是否较低 症状负担将预示患者在生存期间报告的更好的结果。使用临床前小鼠 在口腔癌模型中，我们将研究癌症介导的致敏对肾上腺素能信号传导的影响 体外支配舌头的三叉神经初级传入神经元以及压力的功能影响 体内癌症疼痛行为和相关周围神经可塑性。为了改善结果 HNSCC 幸存者，迫切需要更好地了解 HNSCC 疼痛和压力的患病率 患者以及潜在的生物学机制。