Grant: Operating Grant

In response to various types of pathologies including hypertension and diabetes, sympathetic neurons extend numerous aberrant fibers, which coincide with elevated levels of nerve growth factor (NGF). Following peripheral nerve injury, sympathetic fibers also extend aberrant sprouts into damaged sensory ganglia. In contrast to random sprouting seen in other diseased tissues, sympathetic axons invading the damaged sensory ganglia of adult mammals target individual sensory neurons, forming a basket-like plexus of fibers around cell bodies. This phenomenon, referred to as sympatho-sensory sprouting, has been linked to the development of neuropathic pain conditions (including hyperalgesia and allodynia), which occur following nerve injury. Importantly, destroying aberrant sympathetic axons that invade the affected sensory ganglia in both laboratory animals and humans can alleviate neuropathic pain. In this investigation, we propose a new model for the cellular mechanisms that initiate and sustain the abnormal association between sympathetic axons and sensory neurons that is seen in adult mammals having nerve injury and neuropathic pain behaviors. It is hoped that by gaining a greater understanding of this pathological condition, strategies may be designed to perturb the coupling between sympathetic fibers and sensory neurons induced by nerve injury, and thus counteract the subsequent onset of neuropathic pain.