Small diameter dorsal root ganglion cells can be broadly classified into those that bind Griffonia simplicifolia isolectin IB4 (IB4+) and those that do not bind this lectin (IB4−). These two populations can also be discriminated by the presence of pro-inflammatory peptides and by the expression of neurotrophin receptors; IB4− neurones have high levels of neuropeptides such as calcitonin gene-related peptide and substance P, and express receptors for nerve growth factor, whereas IB4+ neurones are neuropeptide poor and express receptors for glial cell line-derived neurotrophic factor. While both populations are composed of neurones which function as nociceptors, the functional significance of this sub-division remains largely unanswered. However, there is growing evidence that the sensory and biophysical properties IB4– and IB4+ sensory neurones differ between. For example, IB4+ neurones have longer-duration somatic action potentials and larger tetrodotoxin (TTX)-resistant Na+ currents attributable to the α-subunit NaV1.8 (Stucky & Lewin, 1999). It would be predicted that the differential expression of Na+ channel α-subunits between IB4− and IB4+ neurones would have important consequences for their excitability but this has not been extensively investigated. In this issue of The Journal of Physiology, Snape et al. (2010) provide further evidence for the differential expression of Na+ channel α-subunits between IB4− and IB4+ neurons. Firstly they demonstrate that the IB4− neurons are selectively sensitive to the sea anemone toxin ATX-II. As this toxin is relatively selective for the channels NaV1.1 and NaV1.2, it is suggested that one or both may be selectively expressed in IB4− neurons, but this remains to be directly demonstrated. Irrespective of the explanation for the sensitivity to ATX-II, this feature provides strong evidence that the expression of TTX-sensitive Na+ channel α-subunits differs between IB4− and IB4+ neurons and that this has consequences for their excitability (at least in response to this toxin). Secondly the authors demonstrate in IB4+ neurons that excitability increases as the membrane potential is shifted from the normal resting value to ∼−20 mV and attribute this to the high expression of NaV1.8 in these neurons. This conclusion fits well with evidence that sensory nerve endings with these channels are able to sustain the initiation of action potentials when substantially depolarized. In IB4− neurones, excitability peaked ∼10 mV positive of the resting membrane potential and then declined as the membrane was further depolarized, reflecting inactivation of the Na+ channels contributing to the Na+ current. Presumably this behaviour indicates that these neurones will not sustain action potentials during prolonged periods of depolarization (or maintained sensory stimulation). Finally they investigated the mechanisms that contribute to the slowing in conduction velocity that is observed during repetitive activation of C-fibre axons. This feature has been used in microneurography experiments to identify single sensory C-fibres projecting to skin. Importantly, the magnitude of conduction velocity slowing has been shown to differ between sensory neurons with differing modalities (indicating differences in the mechanisms that control excitability; Serra et al. 1999). Recently it has been debated whether the change in conduction velocity results from an increase in Na+/K+ ATPase activity that hyperpolarizes the membrane potential during trains of action potentials (decreasing excitability; Rang & Ritchie, 1968) or the transition of Na+ channels (in particular NaV1.8) into a slow inactivated state (De Col et al. 2008). As Na+ channels recover from slow inactivation slowly, the latter change produces a prolonged decrease in the numbers of Na+ channels available for activation. In IB4+ neurones (but not IB4− neurones), they demonstrated in current clamp that repetitive activation with depolarizing steps produces a pronounced reduction in the derived action current and a delay in action potential initiation. As this change occurred when the ‘resting’ membrane potential was held constant, it cannot be attributed to membrane hyperpolarization. Instead, the change is explained by slow inactivation of NaV1.8 in the IB4+ neurones, supporting the hypothesis that slow inactivation of Na+ channels explains the decrease in conduction velocity (as suggested by De Col et al. 2008). Whether this is the only mechanism remains to be resolved. Together the data presented in this paper provide further functional evidence that the mechanisms regulating excitability differ between IB4− and IB4+ neurones. This new knowledge will prove useful both in investigating and in explaining the differences in sensory phenotypes between these two populations of neurones. The findings also highlight the need to consider the consequences of differential expression of TTX-sensitive Na+ channel α-subunits between IB4− and IB4+ neurones. Recently NaV1.7 (which is relatively insensitive to ATX-II) has been shown to play a key role in nociceptor activation but other TTX (and ATX-II)-sensitive Na+ channel α-subunits must also play an important role in regulating the excitability of IB4− neurones.