The mechanism of a Chinese herbal formula on cancer pain

中药复方治疗癌性疼痛的作用机制

• 批准号: 7946518
• 负责人: LIXING LAO
• 金额: $ 6.21万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7946518
• 关键词: Acupuncture procedure; Adverse effects; Agreement; Alkaline Phosphatase; Analgesics; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Attenuated; Award; Basic Science; Behavioral; Biochemical; Biological Assay; Breast; Cancer Pain Management; Cancer Patient; Carcinoma; China; Chinese Herbs; Chinese People; Chinese Traditional Medicine; Clinical; Clinical Research; Clinical Trials Design; Collaborations; Collagen Type I; Complementary Medicine; Data; Development; Disease; Drug usage; Enzyme-Linked Immunosorbent Assay; Female; Filament; Foundations; Fright; Funding; Gastrointestinal Diseases; Gel; Grant; Health; Herb; Herbal Medicine; Histologic; Hospitals; Human; Hyperalgesia; Institutes; Integrative Medicine; Interdisciplinary Study; International; Investigation; Journals; Laboratories; Laos; Mainstreaming; Malignant Bone Neoplasm; Malignant Neoplasms; Malignant neoplasm of prostate; Maryland; Materia Medica; Measures; Mechanics; Medicine; Metastatic Carcinoma to the Bone; Metastatic Neoplasm to the Bone; Modeling; Monitor; Mus; Opioid; Osteoclasts; Osteogenesis; Outcome; Pain; Pain management; Paper; Patients; Persistent pain; Pilot Projects; Play; Preparation; Prevention; Prostate; Publishing; Qi; Quality of life; Rattus; Reporting; Research; Research Personnel; Research Project Grants; Role; Safety; Scientific Evaluation; Series; Serum; Spinal Ganglia; Staining method; Stains; Stimulus; Symptoms; TRP channel; Thermal Hyperalgesias; Toxic effect; Traditional Medicine; United States National Institutes of Health; Universities; Vanilloid; Withdrawal; allodynia; base; bone; bone metabolism; cancer pain; chemotherapy; crosslink; inflammatory pain; male; malignant breast neoplasm; medical schools; medical specialties; member; molecular marker; pain inhibition; parent grant; pre-clinical; professor; programs; public health relevance; pyridinoline; receptor; research study; spontaneous pain; success; tumor

DESCRIPTION (provided by applicant): the proposed international research study on mechanisims of a Chinese herbal formula on cancer pain is an extension of our ongoing parents grants funded by NIH, P01-AT002605 (9/2005 - 8/201010) and R21 AT 004113 (2/1/08 - 1/31/10). Dr. Lixing Lao, the PI is the project leader of the P01 study on acupuncture's mechanisms of action on persistent inflammatory pain and C0-I of the study on the effect of acupuncture on cancer-related pain. The proposed project will be performed in collaboration with Dr. Ling Xu at Changzheng Hospital (CZ), Shanghai, China. Pain, one of the most common and feared symptoms associated with cancer, is not yet adequately controlled. Chines herbal medicine has been used for thousands of years to treat a variety of ailments, including pain. Dr. Lao and his team have been undertaking investigations on carcionoma-induced pain, and his collaborator, Dr. Ling Xu has been investigating the effect of Traditional Chinese Medicine (TCM) on cancer-related disorders, including pain. Previous studies show that osteoclastic activitiesare involved in bone cancer pain and cause elevated levels of serum bone alkaline phosphatase (BAP) and carboxyterminal pyridlinoline cross-linked telopeptide of type 1 collagen (ICTP). Transient receptor potential channels, vanilloid subfamily member 1 (TRPV1), and TRPA1, and TRPV4 are also involved persistent pain. Our pilot studies showed that an herbal formula, TLSJ, which has been used clinically, alleviated bone cancer pain in patients and in a rat model. The objective of the proposal is to evaluate the efficacy and safety of TLSJ on cancer pain and explore its mechanisms in male and female rat models. We hypothesize that external applications of a TLSJ gel will inhibit cancer pain by suppressing osteoclast activities, evidenced by decrasig levels of serum BAP and ICTA, and TRP channel expression in dorsal root ganglia (DRG). The three aims are: Aim 1 a) To determine the effect of TLSJ Gel on cancer-induced pain in male and female rat models of bone cancer pain. Spontaneious pain, thermal hyperalgesia and mechanical hyperalgesia/allodyna will be determined following herb treatment. b) To determine the safety of TLSJ. Possible adverse effects will be studied by monitoring the animals for behavioral changes, and the toxicity of the formula will be determined by biochemical assay and histological examination. Aim 2. To investigate effects of TLSJ Gel on osteoclasic activity and BAP and ICTP levels during cancer pain. Bone osteeoclastic activity will be hisologically examined. Serum BAP and ICTP will be measured using ELISA. Aim e. To investigate effects of TLSJ Gel on TRP channel expression. TRPV1, TRPA1 and TRPV4 antagonists will be used to characterize TRP involvement in bone cancer pain. DRG expression of the three channels will be examined by immunohistochemical staining. The success of the experiments will provide preliminary data for designing clinical trials to study the effects of Chinese herbs on persistent cancer pain. This will facilitate the development of effective and safe alternative/complementary treatment for cancer pain. PUBLIC HEALTH RELEVANCE: Pain occurs frequently incancerpatients and has not been controlled adequately. Acupuncture has been used for millennia to treat pain. This study will evaluate the effects and mechanisms of an herb formula Tongluo Sanjie (TLSJ) on such pain in rat models. The success of the proposed study will greatly advance the management of cancer pain.

描述（由申请人提供）：拟议的关于中草药配方治疗癌症疼痛机制的国际研究是我们持续由 NIH、P01-AT002605 (9/2005 - 8/201010) 和 R21 AT 004113 资助的父母资助的延伸（2008 年 2 月 1 日 - 2010 年 1 月 31 日）。项目负责人劳力行博士是针灸治疗持续性炎症性疼痛作用机制P01研究和针灸治疗癌症相关疼痛研究C0-I的项目负责人。拟议的项目将与中国上海长征医院 (CZ) 的 Ling Xu 博士合作进行。疼痛是与癌症相关的最常见和最令人恐惧的症状之一，但尚未得到充分控制。几千年来，中草药一直被用来治疗各种疾病，包括疼痛。劳博士和他的团队一直在研究癌引起的疼痛，他的合作者徐凌博士一直在研究中药 (TCM) 对癌症相关疾病（包括疼痛）的影响。先前的研究表明，破骨细胞活动与骨癌疼痛有关，并导致血清骨碱性磷酸酶（BAP）和1型胶原羧基末端吡啶啉交联端肽（ICTP）水平升高。瞬时受体电位通道、香草酸亚家族成员 1 (TRPV1)、TRPA1 和 TRPV4 也与持续性疼痛有关。我们的初步研究表明，一种草药配方 TLSJ 已在临床使用，可以减轻患者和大鼠模型的骨癌疼痛。该提案的目的是评估 TLSJ 对癌性疼痛的疗效和安全性，并探讨其在雄性和雌性大鼠模型中的机制。我们假设 TLSJ 凝胶的外部应用将通过抑制破骨细胞活性来抑制癌痛，血清 BAP 和 ICTA 水平以及背根神经节 (DRG) 中 TRP 通道表达的降低证明了这一点。这三个目标是： 目标 1 a) 确定 TLSJ 凝胶对雄性和雌性骨癌疼痛大鼠模型中癌症引起的疼痛的影响。自发性疼痛、热痛觉过敏和机械痛觉过敏/异常性疼痛将在草药治疗后确定。 b) 确定 TLSJ 的安全性。将通过监测动物的行为变化来研究可能的副作用，并通过生化测定和组织学检查来确定配方的毒性。目标 2. 研究 TLSJ 凝胶对癌性疼痛期间破骨细胞活性以及 BAP 和 ICTP 水平的影响。将对骨破骨细胞活性进行组织学检查。将使用 ELISA 测量血清 BAP 和 ICTP。瞄准 e。研究 TLSJ Gel 对 TRP 通道表达的影响。 TRPV1、TRPA1 和 TRPV4 拮抗剂将用于表征 TRP 参与骨癌疼痛的特征。通过免疫组织化学染色检查三个通道的 DRG 表达。实验的成功将为设计临床试验以研究中药对持续性癌痛的影响提供初步数据。这将有助于开发有效且安全的癌症疼痛替代/补充疗法。 公众健康相关性：癌症患者经常发生疼痛，且尚未得到充分控制。针灸治疗疼痛已有数千年历史。本研究将评估通络散结（TLSJ）对大鼠模型此类疼痛的作用和机制。该研究的成功将极大地推进癌症疼痛的治疗。