Metalloproteinase Inhibitor For Pain and Morphine Tolerance Due To Thermal Injury

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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.