Modulation of neurotrophic growth factors as a therapeutic strategy for neuropathic pain



Neurotrophic growth factors have tremendous untapped potential for the treatment of neurological injuries and diseases. In contrast to specific neurotransmitter modulators or ion channel blockers, a neurotrophic growth factor profoundly impacts multiple molecular pathways within a cell, with the possibility of exerting broad, and potentially “disease-modifying” effects that may counteract the underlying pathology. Although numerous clinical trials have been carried out with the prototypic neurotrophic growth factors, including most notably NGF for diabetic neuropathy and GDNF for Parkinson's disease, none of these trials have been successful to date in providing compelling data for drug approval. The apparent lack of translation from the bench to the clinic may be considered in the context of our current understanding of the neurotrophic growth factors, especially mechanism of action, efficacy in animal models of disease, and safety and tolerability, and how these factors relate to clinical trial design. The application of this new knowledge to future clinical trials of neuropathic pain may provide opportunities for successful clinical development of neurotrophic growth factor modulators. Drug Dev. Res. 67:389–403, 2006. © 2006 Wiley-Liss, Inc.