Nociceptor-like rat dorsal root ganglion neurons express theangiotensin-II AT2 receptor throughout development

Abstract

tAT2 receptor (AT2R) plays a functional role in foetal development. Its expression declines in most tissuessoon after birth but stays high in sensory areas of the adult nervous system. In the dorsal root ganglia (DRG)the expression pattern of AT2R during development and the identity of the subpopulation expressing itremain unknown. Using a combination of semi-quantitative PCR, western blotting and immunohisto-chemistry we examined the expression of AT2R at mRNA and protein levels in rat DRGs from embryonicday 15 (E15) until postnatal day 30 (PN30). We found that both AT2R mRNA and protein levels exhibitedonly minor (statistically non-significant) fluctuations from E15 to PN30. Detailed quantitative analysisof ABC/DAB AT2R staining showed a) that the receptor was present in most neurons at E15 and E18 andb) that postnatally it was predominantly expressed by small DRG neurons. Given that small neurons areputative C-nociceptors and the proposed role of AT2R in neuropathic pain, we next examined whetherthese AT2R-positive neurons co-localized with Ret and trkA embryonically and with IB4-binding post-natally. Most AT2R-positive neurons expressed trkA embryonically and bound IB4 postnatally. We foundstrong positive statistically highly significant correlations between AT2R cytoplasmic%intensities andtrkA at E15/E18 and with Ret only at E18. Cytoplasmic AT2R also strongly and positively correlated withIB4-binding at PN3, 15 and 30. Our demonstration that a subpopulation of C-nociceptor-like neuronsexpresses AT2R during development supports a role for this receptor in neuropathic pain.