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Keywords:

  • auxiliary subunits;
  • chronic constriction injury;
  • DRG;
  • in situ hybridization;
  • neuropathic pain;
  • sodium channel;
  • spinal cord;
  • Sprague–Dawley

Abstract

Adult dorsal root ganglia (DRG) have been shown to express a wide range of voltage-gated sodium channel α-subunits. However, of the auxiliary subunits, β1 is expressed preferentially in only large- and medium-diameter neurons of the DRG while β2 is absent in all DRG cells. In view of this, we have compared the distribution of β1 in rat DRG and spinal cord with a novel, recently cloned β1-like subunit, β3. In situ hybridization studies demonstrated high levels of β3 mRNA in small-diameter c-fibres, while β1 mRNA was virtually absent in these cell types but was expressed in 100% of large-diameter neurons. In the spinal cord, β3 transcript was present specifically in layers I/II (substantia gelatinosa) and layer X, while β1 mRNA was expressed in all laminae throughout the grey matter. Since the pattern of β3 expression in DRG appears to correlate with the TTX-resistant voltage-gated sodium channel subunit PN3, we co-expressed the two subunits in Xenopus oocytes. In this system, β3 caused a 5-mV hyperpolarizing shift in the threshold of activation of PN3, and a threefold increase in the peak current amplitude when compared with PN3 expressed alone. On the basis of these results, we examined the expression of β-subunits in the chronic constriction injury model of neuropathic pain. Results revealed a significant increase in β3 mRNA expression in small-diameter sensory neurons of the ipsilateral DRG. These results show that β3 is the dominant auxiliary sodium channel subunit in small-diameter neurons of the rat DRG and that it is significantly upregulated in a model of neuropathic pain.