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

Patrick W. Mantyh, Martin Koltzenburg, Lorne M. Mendell, Leslie Tive, David L. Shelton

Research output: Contribution to journalReview articlepeer-review

274 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)189-204
Number of pages16
JournalAnesthesiology
Volume115
Issue number1
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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