Metalloproteinase Inhibitor For Pain and Morphine Tolerance Due To Thermal Injury

描述(申请人提供)：Aquilus制药公司提议评估一种专有的基质金属蛋白酶(MMP)抑制剂AQU-010在热损伤(TI)大鼠模型中阻断神经病理性疼痛和吗啡耐受的效果。第一阶段的目标是扩大AQU-010的合成，测定其口服药代动力学(PK)和靶向组织渗透，然后确定其在TI-大鼠机械性和热敏性痛觉异常模型中的疗效。将进行后续生物标记物和明胶酶谱分析，以确定从动物模型中观察到的任何行为变化是否与金属蛋白酶和/或细胞因子水平的变化相对应。这项拟议工作的最终目标是评估基质金属蛋白酶抑制剂是否可以用于治疗烧伤患者的疼痛和/或吗啡耐受性，而不会产生快感和成瘾。

DESCRIPTION (provided by applicant): Aquilus Pharmaceuticals, Inc. proposes to evaluate the effects of a proprietary matrix metalloproteinase (MMP) inhibitor, AQU-010, for blocking neuropathic pain and morphine tolerance in a thermal injury (TI) rat model. The goals for Phase I are to scale-up the synthesis of AQU-010, determine its oral pharmacokinetics (PK) and target tissue penetration and then determine its efficacy in the TI-rat model of mechanical and thermal allodynia. A follow-up biomarker and gelatin zymography analysis will be performed to determine if any behavior changes observed from the animal model correspond to changes in metalloproteinase and/or cytokine levels. The ultimate goal of the proposed work is to evaluate whether a matrix metalloproteinase inhibitor can be used to treat pain and/or morphine tolerance in patients suffering from burn injuries without producing euphoria and addiction.