A NOVEL APPROACH TO STUDY PAIN IN A MOUSE MODEL OF FACIAL BURN INJURY

Burn injury is a major clinical challenge. The causes of burns are vast and diverse, as are the sites of injury. Yet,the overwhelmingly majority of burn victims experience intense spontaneous pain and persistent allodynia, oftenyears after their injury. Opioids are the standard of care for post-burn pain management, but over half of burnvictims report inadequate relief, thereby increasing the risk for prolonged, and even irreversible, disability. Inaddition, opioids clearly exert dangerous side effects that include cognitive dysfunction, respiratory depression,tolerance, and dependence. Accordingly, there is an unquestionable need for research directed atunderstanding mechanisms of post-burn pain to identify novel targets for development of effective analgesicsdevoid of unwanted side effects. Burns to the head and neck are the most common sites of injury and amongstthe most painful for patients. However, to our knowledge, there are no existing animal models of facial burn injuryand this represents a major barrier in solving this severe pain condition. A primary objective of this application isto develop and characterize a rodent model of partial thickness facial burn injury and to employ it to addressorofacial mechanisms of persistent post-burn pain. Clinical studies have revealed that administration of lidocaineby a peripheral nerve block to the site of injury produces robust pain relief, indicating that persistent input fromsensory afferent terminals is a critical mediator of post-burn pain. However, there is a large gap in knowledgeregarding how burn modulates neuronal activity leading to persistent spontaneous pain and modality-specifichypersensitivities beyond complete resolution of the injury itself. Here, we propose to test the central hypothesisthat partial thickness facial burn injury induces transcriptional changes that sensitize sensory neurons andcontribute to the development of persistent hyperalgesia/allodynia. To test the hypothesis, we will: (1) develop amouse model of facial burn injury, and (2) identify transcriptional changes in back-labeled trigeminal ganglianeurons that mediate persistent pain after burn injury. This project has substantial health significance as itproposes an innovative combination of complementary methodologies to elucidate peripheral contributions topersistent post-burn pain. These studies will provide a foundation for future investigation into craniofacial burnpain and ultimately aid in the search for an effective treatment. Moreover, these techniques and researchmethods provide an ideal training vehicle for a career as an academic clinician-scientist.