A Developmental Switch in Acute Sensitization of Small Dorsal Root Ganglion (DRG) Neurons to Capsaicin or Noxious Heating by NGF

Abstract

Using dissociated rat dorsal root ganglion (DRG) neurons, we have explored the ability of nerve growth factor (NGF) to acutely (within minutes) sensitize responses of nociceptors to capsaicin or noxious heat during postnatal development. While robust sensitization of noxious heat or capsaicin responses by NGF is observed in adult DRG neurons, responses to such stimuli in trkA-positive neurons from early postnatal animals are not sensitized by NGF. Neurons acquire sensitivity to the hyperalgesic effects of NGF between postnatal days 4 and 10 (P4-P10). In contrast to NGF, bradykinin sensitizes responses to noxious heat in both adult and neonatal DRG neurons. These observations suggest a developmental switch in signal transduction cascades linking trkA receptors to hyperalgesia during postnatal development and differences in the signaling pathways mediating bradykinin- and NGF-induced sensitization.