Glial cell line-derived neurotrophic factor (GDNF) from adult rat tooth serves a distinct population of large-sized trigeminal neurons.

Glial cell line-derived neurotrophic factor (GDNF) mediates trophic effects for specific classes of sensory neurons. The adult tooth pulp is a well-defined target of sensory trigeminal innervation. Here we investigated potential roles of GDNF in the regulation of adult trigeminal neurons and the dental pulp nerve supply of the rat maxillary first molar. Western blot analysis and radioactive 35S-UTP in situ hybridization revealed that GDNF in the dental pulp and its mRNAs were localized with Ngf in the coronal pulp periphery, in particular in the highly innervated subodontoblast layer. Retrograde neuronal transport of iodinated GDNF and Fluorogold (FG) from the dental pulp indicated that GDNF was transported in about one third of all the trigeminal dental neurons. Of the GDNF-labelled neurons, nearly all (97%) were large-sized (> or =35 microm in diameter). Analysis of FG-labelled neurons revealed that, of the trigeminal neurons supporting the adult dental pulp, approximately 20% were small-sized, lacked isolectin B4 binding and did not transport GDNF. Of the large-sized dental trigeminal neurons approximately 40% transported GDNF. About 90% of the GDNF-accumulating neurons were negative for the high-temperature nociceptive marker VRL-1. Our results show that a subclass of large adult trigeminal neurons are potentially dependent on dental pulp-derived GDNF while small dental trigeminal neurons seems not to require GDNF. This suggests that GDNF may function as a neurotrophic factor for subsets of nerves in the tooth, which apparently mediate mechanosensitive stimuli. As in dorsal root ganglia both small- and large-sized neurons are known to be GDNF-dependent; these data provide molecular evidence that the sensory supply in the adult tooth differs, in some aspects, from the cutaneous sensory system.