Relationship of pronociceptin/orphanin FQ and the nociceptin receptor ORL1 with substance P and calcitonin gene-related peptide expression in dorsal root ganglion of the rat.

Recent evidence suggests a role of prepronociceptin/orphanin FQ (preproN/OFQ) derived neuropeptides in nociceptive signaling. Here, we examined the expression of preproN/OFQ and the nociceptin receptor ORL1 (opioid receptor like receptor 1) in the dorsal root ganglion (DRG) of the rat in relation to that of substance P (SP) and calcitonin gene-related peptide (CGRP). Double labeling in situ hybridization revealed a constitutive expression of preproN/OFQ in a distinct minor subpopulation of very small DRG neurons with no evidence for coexpression with either SP or CGRP. However, a major subpopulation of the preproN/OFQ-positive neurons showed direct juxtaposition to SP and CGRP containing neurons. ORL1 was abundantly expressed with a high degree of coexpression with SP (72%) and CGRP (82%) suggesting that N/OFQ may presynaptically modulate primary sensory nociceptive signaling. The DRG cell line F11 was found to express preproN/OFQ, but not ORL1, and, therefore, is well suited to study the mechanisms of N/OFQ gene regulation in vitro.