Unraveling the story of NGF-mediated sensitization of nociceptive sensory neurons: ON or OFF the Trks?
Nerve Growth Factor (NGF) is produced by and affects a number of immune and inflammatory cells. As part of the inflammatory response, NGF directly or indirectly alters the sensitivity of small diameter sensory neurons that communicate noxious information. The question remains as to the receptors and intracellular signaling cascades that mediate this sensitizing action of NGF. Although the general consensus is that NGF produces peripheral sensitization by activating TrkA, recent work suggests that p75 also contributes. Thus, both NGF receptors appear to contribute to peripheral sensitization although whether they act independently or together remains to be determined. Furthermore, controversy exists as to the downstream signaling pathways involved in NGF-induced peripheral sensitization.
Nicol
Grant D
GD
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Vasko
Michael R
MR
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D053858:Metabolic Networks and Pathways; D051379:Mice; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism*; D009424:Nervous System Physiological Phenomena; D009475:Neurons, Afferent / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D020239:Receptor Cross-Talk; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA