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Accession Number:

AD1168569

Title:

Immunological Contributions to the Chronification of Pain

Author(s):

Author Organization(s):

Report Date:

2021-10-01

Abstract:

The chronification of pain after surgery and other forms of trauma is common, results in suffering, poor functional recovery, and delays return to normal activities. In addition, chronic pain contributes to mood disorders and cognitive decline. Pain after surgery/trauma to the extremities is particularly common and is of high impact in military, Veteran and civilian populations. Emerging data suggest that posttraumatic immune system activation mediated by the formation of autoantibodies contributes to the chronification of pain. Critically, we may have the ability to control posttraumatic immune activation using existing mechanistically distinct, clinically available well-tolerated pharmacological agents. Drugs potently regulating oxidative stress and the activation of B lymphocytes in germinal centers are key in this regard. Our studies make extensive use of a limb fracture model in mice. In work performed to-date we have demonstrated that the activator of nrf2, a transcription element responsive to oxidate stress with the agent dimethyl fumarate (DMF) leads to a reduction in nociceptive and functional changes after limb fracture, a reduction in pain supporting autoantibodies, reduce activation of germinal centers in B lymphocytes and moderate reductions in the production of pain-related cytokines in the skin of fractured animals as well as reduced levels of oxidized protein derivatives. While only the beginning of a 4-year project, we are now positioned to refine our understanding of the roles of oxidative stress and the transition from acute to chronic pain.

Pages:

15

File Size:

1.70MB

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Distribution Statement:

Approved For Public Release

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