Effects of deprivation of neonatal nerve growth factor on the expression of neurotrophin receptors and brain-derived neurotrophic factor by dental pulp afferents of the adult rat

The dental pulp is richly innervated by peptidergic nociceptive neurones that are of special interest because of their central role in dental pain and because they have some features that are not typical of other somatic nociceptors. Here, 35S-riboprobes were used to determine whether pulpal afferents of adult (2-month-old) rats express the nerve growth-factor (NGF) receptors, p75NTR and trkA, which are characteristic of peptidergic nociceptors, and additionally, whether these cells express receptors (trkB and trkC) for other members of the neurotrophin family. In order to begin characterizing the postnatal role of NGF in regulating these neurones, the susceptibility of pulpal afferents to antiserum-mediated early postnatal NGF depletion spanning the period of pulpal innervation development was also examined. In control animals, about 200 trigeminal ganglion cells were labelled after application of the retrograde tracer Fluoro-gold to the first maxillary molar. Among the labelled cells, 79% had positive hybridization signals for p75NTR, 72% for trkA, 34% for trkB, 1% for trkC, and 77% for BDNF. Neonatal NGF depletion reduced the number of retrogradely labelled pulpal afferents by 33%, with numbers of smaller neurones being most strikingly subnormal. This reduction could be attributed to a partial depletion of the neurone population that expressed p75NTR and trkA. Consistent with reports that NGF-responsive neurones also express BDNF, NGF deprivation resulted in a reduction in the number of pulpal afferents that expressed BDNF to an extent similar to that seen for trkA. In contrast, anti-NGF exposure had little effect on the number of pulpal afferents that expressed trkB. These findings indicate that most pulpal afferents in the adult express the NGF receptors p75NTR and trkA, and thus have a continuing potential susceptibility to NGF-mediated regulation of functions such as neuropeptide and BDNF synthesis. However, only a subpopulation of this group of neurones requires NGF in order to develop connections to the pulp during the neonatal period. Few, if any, pulpal afferents express the high-affinity neurotrophin-3 (NT3) receptor trkC, although many have large cell bodies typical of NT3-responsive sensory neurones. A small subpopulation of pulpal afferents seems to express no neurotrophin receptors, yet it is unlikely that these cells belong to the class of small sensory cells known to bind isolectin IB4.