Nasocerebral administration of peptides for temporomandibular joint pain

描述（由申请人提供）：该SBIR旨在利用三叉神经和中枢神经系统的新出现的治疗递送途径-大多数头部和口面部疼痛的最终共同途径来进一步开发头痛治疗。递送途径涉及FDA批准的镇痛肽的鼻内给药，然后将其直接转运至三叉神经疼痛靶标，从而允许递送和靶向，这是迄今为止由于GI/肝过滤器、血源性酶和血脑屏障的障碍而通过标准途径无法实现的。该提案对健康的影响是它有可能减轻涉及4500万美国人的头部和口面部疼痛的不良治疗发病率。使用炎症性颞下颌关节疼痛作为模型，该公司试图探索镇痛肽通过这种鼻内途径递送时的影响。具体地，该提案寻求探索鼻内施用的治疗肽的药效学和药代动力学，以证明镇痛肽在中枢神经系统中的靶点处的递送、靶向和功效。利用行为疼痛模型和放射性标记的摄取和分布研究，该公司将评估这些鼻内镇痛肽用于未来人体临床试验的可行性。口面部和头部疼痛是医疗保健中发病率最高的领域之一，涉及超过4500万美国人。其中最普遍和衰弱的这些疾病是颞下颌关节疼痛。患有这些疾病的人几乎没有选择，残疾和发病率仍然很高。该项目探索了一种治疗这种疾病的新方法，通过鼻内直接将适当的药物递送到三叉神经，大脑和脊髓中的靶点，从而显着提高疗效，同时减少副作用。

DESCRIPTION (provided by applicant): This SBIR seeks to further the development of head pain treatment utilizing a newly emerging therapeutic delivery pathway to the trigeminal nerves and central nervous system - the final common pathway of most head and orofacial pain. The delivery pathway involves the intranasal administration of FDA approved analgesic peptides that are then transported directly to trigeminal pain targets, thus allowing for both delivery and targeting that was heretofore not attainable by standard routes due to obstacles of the GI/hepatic filters, blood borne enzymes, and the blood-brain barrier. The health implications of the proposal are its potential to mitigate the poorly treated morbidity of head and orofacial pain involving upwards of 45 million Americans. Using inflammatory temporomandibular joint pain as a model, the company seeks to explore the impact of analgesic peptides when delivered by this intranasal route. Specifically, the proposal seeks to explore the pharmacodynamics and pharmacokinetics of intranasally administered therapeutic peptides in order to demonstrate delivery, targeting and efficacy of the analgesic peptides at their targets in the central nervous system. Utilizing behavioral pain models and radiolabeled uptake and distribution studies, the company will assess the feasibility of these intranasal analgesic peptides for future human clinical testing. PUBLIC HEALTH RELEVANCE Orofacial and head pain represent one of the largest areas of morbidity in health care, involving upwards of 45 million Americans. One of the most prevalent and debilitating of these diseases is temporomandibular joint pain. Few options are available for those who suffer from these disorders, and disability as well as morbidity remains profound. This project explores a novel approach to treating this disorder by intranasally delivering appropriate drugs directly to their targets in the trigeminal nerves, brain and spinal cord, thus significantly increasing effectiveness while simultaneously reducing side effects.