Neurotrophins and pain

Abstract

There is ample evidence suggesting that neurotrophins in particular nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) regulate pain processing as the modulators. NGF released from local tissue and dorsal root ganglia (DRG) binds to tropomyosin-related kinase (Trk) A receptors and regulates many membrane receptors, ion channels, and signaling molecules contributing to pain processing. Molecules antagonizing NGF-TrkA signaling have been developed and attenuate chronic pain in the patients. However, anti-NGF therapy leads to bone death in some patients suggesting that the therapy antagonizing NGF-TrkA signaling should be cautious to control pain in patients with chronic pain. On the other hand, brain-derived neurotrophic factor (BDNF) may regulate pain as a central modulator. BDNF is released when nociceptors are activated and regulated by NGF. This chapter reviews the roles and the underlying mechanisms by which NGF and BDNF regulate pain processing. The clinical trial of anti-NGF therapy is also discussed.