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Rescuing Our Warriors from Chronic Pain: A Battlefield to Nondeployment Means to Prevent Opioid-induced Amplification of Neuropathic Pain from Traumatic Injury (revised)

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[Technical Report, Annual Report]

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Regents of the University of Colorado

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Based on our preliminary data and a thorough review of the available scientificclinical literature to date, we hypothesize that a Traumaand opioids combine to amplify the intensity and duration of trauma-induced chronic pain. b This combined exposure to trauma plusopioids amplifies the creation and release of endogenous danger signals in spinal cord that create enduring release of TLR4 stimulatorysubstances as a consequence of cell stressdamagedeath, leading to amplified trauma induced chronic pain.Objective 1. Define the response to opioids commonly used for acute pain management, when these are administered early after trauma,prior to development of neuropathic painObjective 2. Define the response to opioids and non-opioids commonly used for neuropathic pain management, when these treatments areadministered later after trauma, after development of neuropathic painObjective 3. Define whether the deleterious effects on neuropathic pain observed in Aims 1 and 2 can be prevented by targeting TLR4 andP2X7Objective 4. Define whether the deleterious effects of analgesics, and positive effects of co-administered TLR4P2X7 antagonists, extendbeyond neuropathic pain to other indices of disability

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[A, Approved For Public Release]