Antagonism of nerve growth factor-TrkA signaling and the relief of pain

Anesthesiology. 2011 Jul;115(1):189-204. doi: 10.1097/ALN.0b013e31821b1ac5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Analgesics / pharmacology*
  • Analgesics / therapeutic use*
  • Animals
  • Brain-Derived Neurotrophic Factor / physiology
  • Disease Models, Animal
  • Humans
  • Nerve Growth Factors / antagonists & inhibitors*
  • Nerve Growth Factors / physiology
  • Neuroma / pathology
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Pain / drug therapy*
  • Receptor, trkA / antagonists & inhibitors*
  • Receptor, trkA / physiology
  • Receptors, Nerve Growth Factor / metabolism
  • Signal Transduction / drug effects


  • Analgesics
  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor
  • Receptor, trkA