Role of NaV1.6 and NaVβ4 Sodium Channel Subunits in a Rat Model of Low Back Pain Induced by Compression of the Dorsal Root Ganglia

•Knock-down of sodium channel subunits NaV1.6 and NaVβ4 reduced pain behaviors in the DRG compression model of low back pain.•The knock-down also reduced sensory neuron hyperexcitability and spontaneous activity, primarily in A-type neurons.•The 2 isoforms play similar roles in two low back pain models, DRG compression and DRG inflammation.•A similar pro-inflammatory cytokine profile is induced by both models, which was not affected by NaVβ4 knock-down.•Targeting the abnormal spontaneous activity mediated by NaV1.6 and NaVβ4 may have therapeutic value. Low back pain is a common cause of chronic pain and disability. It is modeled in rodents by chronically compressing the lumbar dorsal root ganglia (DRG) with small metal rods, resulting in ipsilateral mechanical and cold hypersensitivity, and hyperexcitability of sensory neurons. Sodium channels are implicated in this hyperexcitability, but the responsible isoforms are unknown. In this study, we used siRNA-mediated knockdown of the pore-forming NaV1.6 and regulatory NaVβ4 sodium channel isoforms that have been previously implicated in a different model of low back pain caused by locally inflaming the L5 DRG. Knockdown of either subunit markedly reduced spontaneous pain and mechanical and cold hypersensitivity induced by DRG compression, and reduced spontaneous activity and hyperexcitability of sensory neurons with action potentials