Nav 1.8-Null Mice Show Stimulus-Dependent Deficits in Spinal Neuronal Activity

Background The voltage gated sodium channel Na v 1.8 has a highly restricted expression pattern to predominantly nociceptive peripheral sensory neurones. Behaviourally Na v 1.8-null mice show an increased acute pain threshold to noxious mechanical pressure and also deficits in inflammatory and visceral, but not neuropathic pain. Here we have made in vivo electrophysiology recordings of dorsal horn neurones in intact anaesthetised Na v 1.8-null mice, in response to a wide range of stimuli to further the understanding of the functional roles of Na v 1.8 in pain transmission from the periphery to the spinal cord. Results Na v 1.8-null mice showed marked deficits in the coding by dorsal horn neurones to mechanical, but not thermal, -evoked responses over the non-noxious and noxious range compared to littermate controls. Additionally, responses evoked to other stimulus modalities were also significantly reduced in Na v 1.8-null mice where the reduction observed to pinch > brush. The occurrence of ongoing spontaneous neuronal activity was significantly less in mice lacking Na v 1.8 compared to control. No difference was observed between groups in the evoked activity to electrical activity of the peripheral receptive field. Conclusion This study demonstrates that deletion of the sodium channel Na v 1.8 results in stimulus-dependent deficits in the dorsal horn neuronal coding to mechanical, but not thermal stimuli applied to the neuronal peripheral receptive field. This implies that Na v 1.8 is either responsible for, or associated with proteins involved in mechanosensation.