Development of novel therapeutics for pain and itch relief

开发缓解疼痛和瘙痒的新疗法

• 批准号: 8936338
• 负责人: RU-RONG JI
• 金额: $ 31.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8936338
• 关键词: Action Potentials; Acute; Acute Pain; Acute inflammatory pain; Adjuvant; Adverse effects; Allergic Contact Dermatitis; Analgesics; Antibodies; Behavior; Binding; Biochemistry; Biological Assay; C Fiber; Capsaicin; Cardiac; Cells; Chronic; Data; Development; Disease; Electrophysiology (science); Enzyme-Linked Immunosorbent Assay; Esthesia; Formalin; Generations; Goals; Health; Histamine; Human; Interneurons; Intrathecal Injections; Lead; Life; Mediating; Modeling; Molecular; Molecular Biology; Monoclonal Antibodies; Morphine; Mus; Nerve; Neurons; Nociceptors; Pain; Pathway interactions; Peripheral; Pharmaceutical Preparations; Physiological Processes; Play; Preparation; Qualifying; Rodent Model; Role; Route; Skin; Slice; Sodium Channel; Spinal; Spinal Cord; Spinal Ganglia; Synapses; Synaptic Transmission; Testing; Therapeutic; behavior test; chronic pain; drug development; inflammatory neuropathic pain; inflammatory pain; inhibitor/antagonist; innovation; insight; interdisciplinary approach; mouse model; nerve injury; neural circuit; novel; novel strategies; novel therapeutics; patch clamp; postsynaptic; response; sensor; voltage

DESCRIPTION (provided by applicant): Summary It is estimated that more than 100 million people suffer from chronic pain and more than 30 million people suffer from chronic itch in the U.S. Current therapeutics for chronic pain and itch are inadequate and limited by insufficient efficacy and side effects. Although itch-sensing neurons are a subset of C-fiber nociceptors in dorsal root ganglion, pain and itch are mediated via distinct neural circuits in the spinal cord. There is also crosstalk between pain and itch pathways: pain suppresses itch while analgesic such as morphine can provoke itch. Therefore it will be of great importance to develop new drugs that can target both pain and itch. Toward this goal, we have come up with a novel strategy of developing monoclonal antibodies to treat pain and itch simultaneously. We will employ a multidisciplinary approach that combines molecular biology, biochemistry, electrophysiology in isolated cells, whole DRG preparation, and spinal cord slices, and behavioral testing of pain and itch using evoked and spontaneous responses. Successful accomplishment of the project will not only provide a better understanding of the molecular and synaptic mechanisms of pain and itch sensations but also lead to new therapies for treating debilitating pain and itch conditions.

描述(申请人提供)：摘要据估计，美国有超过1亿人患有慢性疼痛，超过3000万人患有慢性瘙痒。目前治疗慢性疼痛和瘙痒的方法不够充分，而且受到疗效和副作用不足的限制。虽然瘙痒感觉神经元是背根神经节中C纤维伤害性感受器的一个子集，但疼痛和瘙痒是通过脊髓中不同的神经回路来调节的。疼痛和瘙痒之间也存在串扰：疼痛抑制瘙痒，而吗啡等止痛药可能会刺激瘙痒。因此，开发既能针对疼痛又能针对瘙痒的新药将非常重要。为了实现这一目标，我们提出了一种新的策略，即开发单抗来同时治疗疼痛和瘙痒。我们将采用一种多学科的方法，结合分子生物学、生物化学、分离细胞的电生理学、整个DRG准备和脊髓切片，以及使用诱发和自发反应对疼痛和瘙痒的行为测试。该项目的成功完成不仅将提供对疼痛和瘙痒感觉的分子和突触机制的更好理解，还将导致治疗衰弱疼痛和瘙痒状况的新疗法。