Antibodies to Nerve Growth Factor Reverse Established Tactile Allodynia in Rodent Models of Neuropathic Pain without Tolerance
A considerable body of evidence implicates endogenous nerve growth factor (NGF) in conditions in which pain is a prominent feature, including neuropathic pain. However, previous studies of NGF antagonism in animal models of neuropathic pain have examined only the prevention of hyperalgesia and allod...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 322; no. 1; pp. 282 - 287 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.07.2007
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Subjects | |
Online Access | Get full text |
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Summary: | A considerable body of evidence implicates endogenous nerve growth factor (NGF) in conditions in which pain is a prominent
feature, including neuropathic pain. However, previous studies of NGF antagonism in animal models of neuropathic pain have
examined only the prevention of hyperalgesia and allodynia after injury, whereas the more relevant issue is whether treatment
can provide relief of established pain, particularly without tolerance. In the current work, we studied the effects of potent,
neutralizing anti-NGF antibodies on the reversal of tactile allodynia and thermal hyperalgesia in established models of neuropathic
and inflammatory pain in rats and mice. In the complete Freund's adjuvant-induced hind-paw inflammation, spinal nerve ligation
and streptozotocin-induced neuropathic pain models, a single intraperitoneal injection of a polyclonal anti-NGF antibody reversed
established tactile allodynia from approximately day 3 to day 7 after treatment. Effects on thermal hyperalgesia were variable
with a significant effect observed only in the spinal nerve ligation model. In the mouse chronic constriction injury (CCI)
model, a mouse monoclonal anti-NGF antibody reversed tactile allodynia when administered 2 weeks after surgery. Repeated administration
of this antibody to CCI mice for 3 weeks produced a sustained reversal (days 4 to 21) of tactile allodynia that returned 5
days after the end of dosing. In conclusion, NGF seems to play a critical role in models of established neuropathic and inflammatory
pain in both rats and mice, with no development of tolerance to antagonism. Antagonists of NGF, such as fully human monoclonal
anti-NGF antibodies, may have therapeutic utility in analogous human pain conditions. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.106.116236 |