Altered expression of voltage-gated sodium, calcium and potassium channels has been associated with neuropathic pain conditions. In addition, roles for the ligand-gated P2X3 and NMDA receptors, as well as pacemaker HCN channels have also been invoked in the pathogenesis of neuropathic pain. In this chapter, evidence of an important role for post-translational regulation of Nav1.9 in setting pain thresholds is presented. Despite the importance of tactile allodynia and mechanical hyperalgesia in chronic pain, we remain ignorant of the molecular nature of mechanosensors present in sensory neurons. A number of candidate mechanosensor genes, identified because of their structural similarity with mechanosensors in Caenorbabditis elegans and Drosophila melanogaster have been identified. Acid-sensing ion channels (ASICs) are structurally related to putative mechanosensors in C. elegans, whilst transient receptor potential channels (TRPs) have been implicated in mechanosensation in the Drosophila acoustic system. Evidence against a role for ASICs as primary transducers of mechanosensation is provided here, and recent evidence implicating TRP channels is reviewed. Finally, the use of sensory neuron-specific gene deletion approaches to unravel the significance of individual ion channels in the regulation of sensory neuron excitability and the induction of pain will be described.