Intense Isolectin-B4 Binding in Rat Dorsal Root Ganglion Neurons Distinguishes C-Fiber Nociceptors with Broad Action Potentials and High Nav1.9 Expression

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Abstract
Binding to isolectin-B4 (IB4) and expression of tyrosine kinase A (trkA) (the high-affinity NGF receptor) have been used to define two different subgroups of nociceptive small dorsal root ganglion (DRG) neurons. We previously showed that only nociceptors have high trkA levels. However, information about sensory and electrophysiological properties in vivo of single identified IB4-binding neurons, and about their trkA expression levels, is lacking. IB4-positive (IB4+) and small dark neurons had similar size distributions. We examined IB4-binding levels in >120 dye-injected DRG neurons with sensory and electrophysiological properties recorded in vivo. Relative immunointensities for trkA and two TTX-resistant sodium channels (Nav1.8 and Nav1.9) were also measured in these neurons. IB4+ neurons were classified as strongly or weakly IB4+. All strongly IB4+ neurons were C-nociceptor type (C-fiber nociceptive or unresponsive). Of 32 C-nociceptor-type neurons examined, ∼50% were strongly IB4+, ∼20% were weakly IB4+ and ∼30% were IB4−. Aδ low-threshold mechanoreceptive (LTM) neurons were weakly IB4+ or IB4−. All 33 A-fiber nociceptors and all 44 Aα/β-LTM neurons examined were IB4−. IB4+ compared with IB4− C-nociceptor-type neurons had longer somatic action potential durations and rise times, slower conduction velocities, more negative membrane potentials, and greater immunointensities for Nav1.9 but not Nav1.8. Immunointensities of IB4 binding in C-neurons were positively correlated with those of Nav1.9 but not Nav1.8. Of 23 C-neurons tested for both trkA and IB4, ∼35% were trkA+/IB4+ but with negatively correlated immunointensities; 26% were IB4+/trkA−, and 35% were IB4−/trkA+. We conclude that strongly IB4+ DRG neurons are exclusively C-nociceptor type and that high Nav1.9 expression may contribute to their distinct membrane properties.

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