@article{5eb70b0908ad45b8a3cb9e042c886867,
title = "Antagonism of nerve growth factor-TrkA signaling and the relief of pain",
abstract = "Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However, in the adult NGF has been found to play an important role in nociceptor sensitization after tissue injury. The authors outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. The authors also document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events and how humans may change their behavior and use of the injured/degenerating tissue after significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF.",
author = "Mantyh, {Patrick W.} and Martin Koltzenburg and Mendell, {Lorne M.} and Leslie Tive and Shelton, {David L.}",
note = "Funding Information: Received from the Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona. Submitted for publication August 24, 2010. Accepted for publication February 24, 2011. Supported by National Institutes of Health (Bethesda, Maryland) grant Nos. NS23970 (to Dr. Mantyh) and 5RO1 NS 16996 (to Dr. Mendell); the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (Washington, D.C.) grant Nos. O4380-I and A6707-R (to Dr. Mantyh); the Brain Research Trust (London, United Kingdom; to Dr. Koltzenburg); the Department of Health's Comprehensive Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust (London, United Kingdom; to Dr. Koltzenburg), and the Medical Research Council (London, United Kingdom; to Dr. Koltzenburg); the Christopher and Dana Reeve Foundation grant No. LMC-2010 (Short Hills, New Jersey; to Dr. Mendell); and the William Heiser Foundation (Wantagh, New York; to Dr. Mendell). Dr. Mantyh received anti-nerve growth factor as a research tool and gift from Rinat Laboratories, Pfizer Inc (South San Francisco, California). Dr. Mendell's neurotrophin research has been aided by gifts of brain-derived nerve growth factor and neurotrophin-3 from Regeneron Pharmaceuticals Inc (Tarrytown, New York), and nerve growth factor and neurotrophin-4/5 from Genentech, Inc (South San Francisco, California). Dr. Mantyh has served as a consultant for and had research grants from Abbott (Abbott Park, Illinois), Adolor (Exton, Pennsylvania), Array Biopharma (Boulder, Colorado), Johnson and Johnson (New Brunswick, New Jersey), Pfizer (New York, New York), Plexxikon (Berkeley, California), and Roche (South San Francisco, California). In the past 3 years, Dr. Koltzenburg has served as a consultant for AstraZeneca (S{\"o}dertalje, Sweden), Endo (Chadds Ford, Pennsylvania), Johnson and Johnson (New Brunswick, New Jersey), Gr{\"u}nenthal (Aachen, Germany), Merck (Whitehouse Station, New Jersey), Novartis Pharmaceuticals UK (Horsham, United Kingdom), Organon (Oss, The Netherlands), Quintiles (Durham, North Carolina), Pfizer (New York, New York), QRX Pharma (Bedminster, New Jersey), and Schering-Plough (Kenilworth, New Jersey). Dr. Mendell has served as a consultant for Genentech, Inc (South San Francisco, California) and Pfizer, Inc (New York, New York). Dr. Tive is an employee of Pfizer Inc. Dr. Shelton is an employee of Rinat Laboratories, Pfizer Inc. Karen Burrow and Aideen Young wrote the first rough draft of the manuscript in September 2009. Drs. Mantyh, Koltzenburg, Mendell, Shelton, and Tive then extensively edited and rewrote the manuscript in 20 separate drafts during the next 12 months. Dr. Mantyh served as the lead author in rewriting, deleting, and adding new material and sections to the manuscript; he also drew the rough outlines of the figures. Drs. Mantyh, Koltzenburg, and Mendell are responsible for the views and opinions of this manuscript and did not receive any fees or compensation for the writing of this review. Figures 1–3 and 5 in this article were prepared by Annemarie B. Johnson, C.M.I., Medical Illustrator, Wake Forest University School of Medicine Creative Communications, Wake Forest University Medical Center, Winston-Salem, North Carolina. ",
year = "2011",
month = jul,
doi = "10.1097/ALN.0b013e31821b1ac5",
language = "English (US)",
volume = "115",
pages = "189--204",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "1",
}