Spontaneous pain, a poorly understood aspect of human neuropathic pain, is indicated in animals by spontaneous foot lifting (SFL).

We have examined the distribution of the sensory neuron-specific Na + channel Na v 1.8 (SNS/PN3) in nociceptive and non-nociceptive dorsal root ganglion (DRG) neurons and whether its distribution is related to neuronal membrane properties. Na v 1.8-like immunoreactivity (Na v 1.8-LI) was examined with an affinity purified polyclonal antiserum (SNS11) in rat DRG neurons that were classified according to sensory receptive properties and by conduction velocity (

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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 (IB4ϩ) and small dark neurons had similar size distributions. We examined IB4-binding levels in Ͼ120 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. IB4ϩ neurons were classified as strongly or weakly IB4ϩ.All strongly IB4ϩ neurons were C-nociceptor type (C-fiber nociceptive or unresponsive). Of 32 C-nociceptor-type neurons examined, ϳ50% were strongly IB4ϩ, ϳ20% were weakly IB4ϩ and ϳ30% were IB4Ϫ. A␦ low-threshold mechanoreceptive (LTM) neurons were weakly IB4ϩ or IB4Ϫ. All 33 A-fiber nociceptors and all 44 A␣/␤-LTM neurons examined were IB4Ϫ. IB4ϩ compared with IB4Ϫ 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, ϳ35% were trkAϩ/IB4ϩ but with negatively correlated immunointensities; 26% were IB4ϩ/trkAϪ, and 35% were IB4Ϫ/trkAϩ. We conclude that strongly IB4ϩ DRG neurons are exclusively C-nociceptor type and that high Nav1.9 expression may contribute to their distinct membrane properties.