title: Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor.
abstract: Nerve growth factor (NGF) is critical for the development and maintenance of sympathetic and sensory neurons in the developing nervous system, including nociceptors. In the adult nervous system, NGF is known to produce significant pain signals by binding to the TrkA and p75NTR receptors. Several pathological pain disorders are associated with nerve growth factor dysregulation, including neuropathic pain, osteoarthritic pain, and hyperalgesia. Currently, clinical management of these pathologies has relied on the use of opioid and non-steroidal anti-inflammatory drugs (NSAID). However, several chronic pain conditions demonstrate insensitivity to NSAID treatment or the development of detrimental opioid-related side effects, including addiction. As NGF plays an important role in pain generation; antibodies, small molecules and peptides have been designed to antagonize NGF. In this review, we discuss the structural biology of NGF ligand/receptor interaction, and we review current biological and pharmacological strategies to modulate NGF-related pathologies.
authors.affiliation: Northern Ontario School of Medicine, Medical Science Division, East Campus, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Eibl
authors.forename: Bridget C
authors.initials: BC
authors.lastname: Strasser
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Ross
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008024:Ligands; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D010455:Peptides; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA; C549319:tanezumab