Development of novel therapeutics for pain and itch relief

据估计，在美国有超过1亿人患有慢性疼痛，超过3000万人患有慢性瘙痒。目前，针对慢性疼痛和瘙痒的治疗方法不足，并且受到疗效不足和副作用的限制。虽然瘙痒感觉神经元是背根神经节c纤维伤害感受器的一个子集，但疼痛和瘙痒是通过脊髓中不同的神经回路介导的。疼痛和瘙痒通路之间也存在相互作用：疼痛抑制瘙痒，而止痛剂如吗啡则会引起瘙痒。因此，开发既能治疗疼痛又能治疗瘙痒的新药具有重要意义。为了实现这一目标，我们提出了一种开发单克隆抗体同时治疗疼痛和瘙痒的新策略。我们将采用多学科方法，结合分子生物学、生物化学、分离细胞电生理学、整个DRG制备和脊髓切片，以及使用诱发和自发反应对疼痛和瘙痒进行行为测试。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，而且还将导致治疗衰弱性疼痛和瘙痒疾病的新疗法。

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.