A number of recent studies indicate that target-derived neurotrophins platy a major role in tissue and nerve injury-induce patin states. This proposal seeks to address currently unexplored effects of locally synthesized brain derived neurotrophic factor (BDNF) in that pathophysiology of neuropathic pain. BDNF is known to alter neuronal phenotype and to induce neuronal sprouting and synaptic plasticity; these are the hallmarks of nerve injury. Nerve injury increased BDNF mRNA in dorsal root ganglion (DRG), suggesting a possibility of BDNF's involvement in these change. Also, nerve injury increases trkB (BDNF receptor) mRNA in DRG, probably due at least in part to its expression in neurons that normally do not express it. As this effect may be important for the pathophysiology of neuropathic pain, we will use immunostaining technique to identify DRG neuronal subpopulations that express BDNF and trkB after the injury. In addition, we will use continuous intrathecal infusion of BDNF antisense oligonucleotides to decreased BDNF bioavailability, and assess BDNF's role in nerve injury- induced alteration of neuronal phenotype an aberrant sprouting. Finally, using behavioral tests of nociception on nerve-injured animals to associate with BDN depletion, we will test the hypothesis that BDNF- induced changes in neuronal plasticity contribute to the nerve injury- induced pain conditions.
