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(申请人提供)：拟议中的癌症疼痛中草药配方的机理国际研究是由NIH，P01-AT002605(9/2005-8/201010)和R21 AT 004113(2/1/08-1/31/10)资助的持续父母资助的延伸。罗立兴博士是P01针灸治疗持续性炎症性疼痛作用机制研究的项目负责人，也是针灸治疗癌症相关疼痛研究的C0-I项目负责人。拟议的项目将与上海长征医院的徐玲医生合作进行，中国说。疼痛是与癌症相关的最常见和最令人恐惧的症状之一，目前还没有得到充分的控制。几千年来，中国的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进行癌症引起的疼痛的研究，他的合作者凌旭博士一直在研究中医药对包括疼痛在内的癌症相关疾病的作用。以往的研究表明，破骨细胞活动参与了骨癌疼痛，并导致血清骨碱性磷酸酶(BAP)和1型胶原羧基末端吡咯啉交联端肽(ICTP)水平升高。瞬时受体电位通道、香草样物质家族成员1(TRPV1)、TRPA1和TRPV4也与持续性疼痛有关。我们的初步研究表明，已在临床上使用的草药配方TLSJ可以缓解患者和大鼠模型的骨癌疼痛。本研究的目的是在雄性和雌性大鼠模型上评价TLSJ对癌痛的疗效和安全性，并探讨其机制。我们假设TLSJ凝胶的外用将通过抑制破骨细胞的活性来抑制癌症疼痛，这一点从血清BAP和ICTA的降低水平以及背根神经节(DRG)的Trp通道表达中得到了证明。本研究的三个目的是：1)研究通络散结凝胶对骨癌痛雄性和雌性大鼠癌性疼痛的影响。自发性疼痛、热痛觉过敏和机械性痛觉过敏/痛觉过敏将在草药治疗后确定。B)确定TLSJ的安全性。可能的副作用将通过监测动物的行为变化来研究，该配方的毒性将通过生化分析和组织学检查来确定。目的：观察通络生骨颗粒对癌痛小鼠骨矿活性及骨钙素(BAP)、细胞间黏附蛋白(ICTP)水平的影响。将对破骨细胞活性进行组织学检查。采用双抗体夹心法测定血清BAP和ICTP。目的：研究TLSJ凝胶对色氨酸通道表达的影响。TRPV1、TRPA1和TRPV4拮抗剂将被用来表征TRP参与骨癌疼痛的特征。用免疫组织化学方法检测三种通道的DRG表达。实验的成功将为设计临床试验以研究中草药对顽固性癌症疼痛的影响提供初步数据。这将有助于开发有效和安全的癌症疼痛替代/补充治疗方法。 公共卫生相关性：疼痛经常发生在癌症患者身上，而且没有得到充分的控制。针灸治疗疼痛已有数千年的历史。本研究旨在探讨通络散结对大鼠痛觉障碍的治疗作用及其机制。这项拟议研究的成功将极大地推动癌症疼痛的管理。