Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor

Nociceptive dorsal root ganglion (DRG) cells can be divided into three main populations, namely (1) small diameter non-peptide-expressing cells, (2) small-diameter peptide-expressing (calcitonin gene related peptide (CGRP), substance P) cells, and (3) medium-diameter peptide-expressing (CGRP) cells. The properties of these cell populations will be reviewed, with a special emphasis on the expression of the vanilloid (capsaicin) receptor VR1 and its regulation by growth factors. Cells in populations 1 and 2 express VR1, a nonselective channel that transduces certain nociceptive stimuli and that is crucial to the functioning of polymodal nociceptors. Cells in population 1 can be regulated by glial cell line derived neurotrophic factor (GDNF) and those in populations 2 and 3 by nerve growth factor (NGF). In vivo, DRG cells express a range of levels of VR1 expression and VR1 is downregulated after axotomy. However, treatment with NGF or GDNF can prevent this downregulation. In vitro, DRG cells also show a range of VR1 expression levels that is NGF and (or) GDNF dependent. Functional studies indicate that freshly dissociated cells also show differences in sensitivity to capsaicin. The significance of this is not known but may indicate a difference in the physiological role of cells in populations 1 and 2.