Spinal cord injury (SCI) can result in hyperexcitability of dorsal horn neurons and central
neuropathic pain. We hypothesized that these phenomena are consequences, in part, of dysregulated expression of
voltage-gated sodium channels. Because the rapidly repriming TTX-sensitive
sodium channel Nav1.3 has been implicated in peripheral
neuropathic pain, we investigated its role in central
neuropathic pain after SCI. In this study, adult male Sprague Dawley rats underwent T9 spinal
contusion injury. Four weeks after injury when extracellular recordings demonstrated hyperexcitability of L3-L5 dorsal horn multireceptive nociceptive neurons, and when
pain-related behaviors were evident, quantitative RT-PCR, in situ hybridization, and immunocytochemistry revealed an upregulation of Nav1.3 in dorsal horn nociceptive neurons. Intrathecal administration of antisense
oligodeoxynucleotides (ODNs) targeting Nav1.3 resulted in decreased expression of Nav1.3
mRNA and
protein, reduced hyperexcitability of multireceptive dorsal horn neurons, and attenuated
mechanical allodynia and
thermal hyperalgesia after SCI. Expression of Nav1.3
protein and hyperexcitability in dorsal horn neurons as well as
pain-related behaviors returned after cessation of antisense delivery. Responses to normally noxious stimuli and motor function were unchanged in SCI animals administered Nav1.3 antisense, and administration of mismatch ODNs had no effect. These results demonstrate for the first time that Nav1.3 is upregulated in second-order dorsal horn sensory neurons after
nervous system injury, showing that SCI can trigger changes in
sodium channel expression, and suggest a functional link between Nav1.3 expression and neuronal hyperexcitability associated with central
neuropathic pain.