Neurofibromatosis and the Painful Neuroma

Pain is a common and distressing symptom that impacts the quality of life of many patients with neurofibromatosis. The pain is often due to the formation of a neuroma. To understand better how neuromas cause pain and what treatments may be provided, we have developed an animal model of a painful neuroma. The tibial neuroma transposition (TNT) model has been confirmed as a model of neuropathic pain. The TNT model has been established as reliable and valid (Specific Aim 1). In the TNT model, the neuroma test-site mechanosensitivity is dependent on neural input from the tibial neuroma. In the TNT model, hindpaw mechanical hyperalgesia is independent of input from the tibial neuroma. We have altered the formation of a neuroma by applying a toxin that is retrogradely transported (suicide transport) leading to neuronal death and axonal death (Specific Aim 2). Application of target specific toxins will lead to death of various populations of axons. The TNT model clearly demonstrates that axons surviving suicide transport can maintain the pain behaviour associated with neuroma sensitivity. Complete obliteration of axons in the robust TNT model is required for cessation of neuroma pain (Specific Aim 3).
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