Figure 1.

NGF signaling pathways in mediating neurotrophic and nociceptor effects.

Notes: NGF signals through the high-affinity TrkA and low p75^NTR receptors. TrkA activates both PI3 kinase (PI3K) and Ras pathways, which lead to cell survival and neurite outgrowth. Signaling through p75^NTR leads to apoptosis, which is blocked by the TrkA-activated PI3K pathway. PI3K activation also leads to activation of the nonselective cation channel TRPV1 by phosphorylation, thereby generating action potential for nociceptive functions. Moreover, TRPV1 phosphorylation results in increased translocation of TRPV1 to the plasma membrane to enhance channel activity. Antibody-mediated NGF blockade results in the abolition of both neurotrophic and nociceptor functions.

Abbreviation: NGF, nerve growth factor.