Use of PC‐NSAIDs to treat 2nd degree burn injury in rodent models

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BackgroundThere is a need for drug treatment for 2nd degree burn injury that can be applied quickly to both relieve pain and promote healing. Currently used drugs for chronic pain have substantial side‐effects which limit their usefulness. These include opioids and their addictive potential, gabapentin and its sedation, and coxibs with their risk of cardiovascular failure. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are potent analgesics and provide relief from burn pain, but their use is limited due to side effects related to gastrointestinal (GI) bleeding insusceptible patients.Objective/AimThe goal of this project is to develop rodent model systems to evaluate the analgesic efficacy and side‐effects of a novel treatment for 2nd degree burn injury to alleviate pain and promote healing using a new class of NSAIDs that are complexed with the soy phosphatidylcholine (PC) that can be administered as a sterile topical alone, parenterally or in combination.MethodsEmploying two established methods, for the induction of 2nd degree burn injury in rats to either the dorsal skin or the hindlimb we investigated the effects of the PC‐NSAIDs, Ibuprofen‐PC and Indomethacin‐PC vs the unmodified NSAIDs administered (either subcutaneously (sc) or topically to the affected skin) daily over a 10‐day study at a dose of 20 mg/kg and 2mg/kg respectively. We then assessed pain sensation behaviorally, the depth of skin injury by light and fluorescent microscopy and tissue inflammation biochemically and by non‐invasive IVIS imaging.Results & ConclusionBoth Indomethacin‐PC and Ibuprofen‐PC when sc administered provided moderate hyperalgesia at 3‐ and 5‐days post‐burn injury, which was similar to the unmodified NSAIDs and in some cases more efficacious as analgesic/anti‐inflammatory agents. Topical administration of our test PC‐NSAIDs provided more variable responses using the two rodent model systems, with the most consistent analgesic/anti‐inflammatory effect being recorded with Indomethacin‐PC. Morphological analysis revealed that the depth of skin injury was reduced in rats treated with the PC‐NSAIDs with no evidence of GI bleeding. Supported by a USARMC grant, W81XWH‐14‐2‐0016.Support or Funding InformationSupported by a USARMC grant, W81XWH‐14‐2‐0016.