Nerve injury can affect anyone and carries consequences that last forever and traumatic peripheralnerve injury (TPNI) can result from settings as diverse as battlefield or motor vehicle trauma to iatrogenicinjury from surgical treatments of other serious conditions. For other tissue types the prognosis and treatmentplan are straightforward. However when nerves fail doctors have few tools to help guide the treatment planand patients forever remember their experiences with pain and paralysis. If nerve injuries can happen frommany causes what is the determinant that most predicts a good outcome? The answer is nerve continuity. A nerve that has been severed say by a bullet will never heal withoutsurgical repair and yet that same nerve grazed by the bullet or caught in the shockwave of a passing bulletis indistinguishable from the nerve cut by the bullet. Both nerves do not work and yet the latter unseverednerve is best left to recover on its own without surgery. Two types of nerve injury exist both yield nerves thatare equally dysfunctional and yet we need to surgically repair one whereas surgery is detrimental to the other.No test exists to tell these nerves apart until weeks have passed after the injury. After weeks have passed weuse electrodiagnostics (EDX) to tell which nerves were severed. This is the state of the art in TPNI diagnosis. Because continuity of the nerve is itself impossible to define for weeks after injury the current standardtreatment is waiting for spontaneous recovery in most patients we guess do not have a severed nerve. Inevery field of medicine there are nerve injuries monitored in this way - without tools for definitive diagnosisbased on our clinical suspicion. We recently discovered that a current FDA-approved drug (4-aminopyridine 4AP) has the previouslyunknown effect of immediately allowing diagnosis of traumatically paralyzed nerves. Small doses candistinguish the severed nerve which requires immediate surgery from the non-severed nerve which can besafely monitored. This novel property of 4AP a drug already used in humans may be explored while we waitfor function to spontaneously return. Based on our preliminary data we intend to repurpose 4AP to diagnosenerve discontinuity instead of just guessing if the nerve is severed and hoping for recovery. We want to try 4AP in patients who have nerve injury where we cannot tell if the nerve was severed ornot. We obtained FDA approval for a trial of 4AP in humans to investigate nerve continuity and have modifiedour institutional IRB approval to proceed. We want to test 4AP in humans with TPNI in a novel way: As apharmacologic diagnostic where the results of a challenge with the drug reveal something about theunderlying nerve continuity. With the knowledge gained from this trial we hope to provide solid informationthat can confirm or refute clinical guesswork on the critical issue of nerve continuity.