title: Nerve growth factor mediates hyperalgesia and cachexia in auto-immune arthritis.
abstract: Pain and cachexia are two of the most debilitating aspects of rheumatoid arthritis. Despite that, the mechanisms by which they are mediated are not well understood. We provide evidence that nerve growth factor (NGF), a secreted regulatory protein that controls neuronal survival during development, is a key mediator of pain and weight loss in auto-immune arthritis. Function blocking antibodies to NGF completely reverse established pain in rats with fully developed arthritis despite continuing joint destruction and inflammation. Likewise, these antibodies reverse weight loss while not having any effect on levels of the pro-cachectic agent tumor necrosis factor (TNF). Taken together, these findings argue that pathological joint pain and joint destruction are mechanistically independent processes and that NGF regulates an alternative cachexia pathway that is independent or downstream of TNF.
authors.affiliation: Rinat Neuroscience Corp., 3155 Porter Drive, Palo Alto, CA 94304, USA. shelton@rinatneuro.com
authors.forename: David L
authors.initials: DL
authors.lastname: Shelton
authors.forename: Jörg
authors.initials: J
authors.lastname: Zeller
authors.forename: Wei-Hsien
authors.initials: WH
authors.lastname: Ho
authors.forename: Jaume
authors.initials: J
authors.lastname: Pons
authors.forename: Arnon
authors.initials: A
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications; D002100:Cachexia / Q000209:etiology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000628:therapy*; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D020932:Nerve Growth Factor / Q000276:immunology / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D029968:Escherichia coli Proteins; D016211:Transforming Growth Factor alpha; D020932:Nerve Growth Factor; D007213:Indomethacin