Novel class of pain drugs based on antagonism of NGF.
Nerve growth factor (NGF) was identified originally as a survival factor for sensory and sympathetic neurons in the developing nervous system. In adults, NGF is not required for survival but it has a crucial role in the generation of pain and hyperalgesia in several acute and chronic pain states. The expression of NGF is high in injured and inflamed tissues, and activation of the NGF receptor tyrosine kinase trkA on nociceptive neurons triggers and potentiates pain signalling by multiple mechanisms. Inhibition of NGF function and signalling blocks pain sensation as effectively as cyclooxygenase inhibitors and opiates in rodent models of pain. Several pharmaceutical companies have active drug-discovery and development programs that are based on a variety of approaches to antagonise NGF, including NGF 'capture', blocking the binding of NGF to trkA and inhibiting trkA signalling. NGF antagonism is expected to be a highly effective therapeutic approach in many pain states, and to be free of the adverse effects of traditional analgesic drugs.
Hefti
Franz F
FF
Rinat Neuroscience Corporation, 230 East Grand Avenue, South San Francisco, CA 94080, USA.
Rosenthal
Arnon
A
Walicke
Patricia A
PA
Wyatt
Sean
S
Vergara
German
G
Shelton
David L
DL
Davies
Alun M
AM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D020917:Receptor, trkA / Q000037:antagonists & inhibitors; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D020917:Receptor, trkA