Nerve growth factor mediates hyperalgesia and cachexia in auto-immune arthritis.
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.
Shelton
David L
DL
Rinat Neuroscience Corp., 3155 Porter Drive, Palo Alto, CA 94304, USA. shelton@rinatneuro.com
Zeller
Jörg
J
Ho
Wei-Hsien
WH
Pons
Jaume
J
Rosenthal
Arnon
A
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D029968:Escherichia coli Proteins; D016211:Transforming Growth Factor alpha; D020932:Nerve Growth Factor; D007213:Indomethacin