Unraveling the Story of NGF-mediated Sensitization of Nociceptive Sensory Neurons: ON or OFF the Trks?

• Published in: Molecular interventions Vol. 7; no. 1; pp. 26 - 41
• Main Authors: Nicol, Grant D, Vasko, Michael R
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.02.2007
• Subjects: Animals; Cells, Cultured; Gene Expression Regulation - physiology; Metabolic Networks and Pathways; Mice; Nerve Growth Factor - drug effects; Nerve Growth Factor - metabolism; Nervous System Physiological Phenomena; Neurons, Afferent - metabolism; Nociceptors - drug effects; Nociceptors - metabolism; PC12 Cells; Rats; Receptor Cross-Talk; Receptor, Nerve Growth Factor - metabolism; Receptor, trkA - metabolism; Receptors, Nerve Growth Factor - metabolism; Signal Transduction
• ISSN: 1534-0384; 1543-2548
• DOI: 10.1124/mi.7.1.6

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.