Although hyperexcitability and/or increased baseline sensitivity of primary sensory neurons following nerve injury can lead to abnormal burst activity associated with pain, the molecular mechanisms that contribute to it are not fully understood. Early studies demonstrated that, following axonal injury, neurons can display changes in excitability suggesting increased sodium channel expression. Consistent with this, abnormal accumulations of sodium channels have been observed at the tips of injured axons. But we now know that nearly a dozen distinct sodium channels are encoded by different genes, raising the question, what types of sodium channels underlie hyperexcitability of primary sensory neurons following injury? My laboratory has used molecular, electrophysiological, and pharmacological techniques to answer this question. Our studies have demonstrated that multiple sodium channels, with distinct physiological properties, are expressed within small dorsal root ganglion (DRG) neurons, which include nociceptive cells. Several DRG and trigeminal neuron-specific sodium channels have now been cloned and sequenced. There is a dramatic change in sodium channel expression in DRG neurons, with down-regulation of the SNS/PN3 and NaN sodium channel genes and up-regulation of previously silent Type III sodium channel gene, following injury to the axons of these cells. These changes in sodium channel gene expression can produce electrophysiological changes in DRG neurons which poise them to fire spontaneously or at inappropriate high frequencies. We have also observed changes in sodium channel gene expression in experimental models of inflammatory pain. The dynamic nature of sodium channel gene expression in DRG neurons, and the changes which occur in sodium channel and sodium current expression in these cells following axonal injury and in inflammatory pain models, suggest that abnormal expression of sodium channels contributes to the molecular pathophysiology of pain.