Characteristics of sensory neuronal groups in CGRP-cre-ER reporter mice: Comparison to Nav1.8-cre, TRPV1-cre and TRPV1-GFP mouse lines

Peptidergic sensory neurons play a critical role in nociceptive pathways. To precisely define the function and plasticity of sensory neurons in detail, new tools such as transgenic mouse models are needed. We employed electrophysiology and immunohistochemistry to characterize in detail dorsal root ganglion (DRG) neurons expressing an inducible CGRP(cre-ER) (CGRP-cre(+)); and compared them to DRG neurons expressing Nav1.8(cre) (Nav1.8-cre(+)), TRPV1(cre) (TRPV1-cre(+)) and TRPV1-GFP (V1-GFP(+)). Tamoxifen effectively induced CGRP(cre-ER) production in DRG. ≈87% of CGRP(cre-ER)-expressing neurons were co-labeled CGRP antibody. Three small and two medium-large-sized (5HT3a(+)/NPY2R(-) and NPY2R(+)) neuronal groups with unique electrophysiological profiles were CGRP-cre(+). Nav1.8-cre(+) neurons were detected in all CGRP-cre(+) groups, as well as in 5 additional neuronal groups: MrgprD(+)/TRPA1(-), MrgprD(+)/TRPA1(+), TRPV1(+)/CGRP(-), vGLUT3(+) and ≈30% of trkC(+) neurons. Differences between TRPV1(cre) and Nav1.8(cre) reporters were that unlike TRPV1-cre(+), Nav1.8-cre(+) expression was detected in non-nociceptive vGLUT3(+) and trkC(+) populations. Many TRPV1-cre(+) neurons did not respond to capsaicin. In contrast, V1-GFP(+) neurons were in 4 groups, each of which was capsaicin-sensitive. Finally, none of the analyzed reporter lines showed cre-recombination in trkB(+), calbindin(+), 70% of trkC(+) or parvalbumin(+) neurons, which together encompassed ≈20% of Nav1.8-cre(-) DRG neurons. The data presented here increases our knowledge of peptidergic sensory neuron characteristics, while showing the efficiency and specificity manipulation of peptidergic neurons by the CGRP(cre-ER) reporter. We also demonstrate that manipulation of all C- and A-nociceptors is better achieved with TRPV1-cre reporter. Finally, the described approach for detailed characterization of sensory neuronal groups can be applied to a variety of reporter mice.