Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice

Changes in sodium channel activity and neuronal hyperexcitability contribute to neuropathic pain, a major clinical problem. There is strong evidence that the re-expression of the embryonic voltage-gated sodium channel subunit NavI.3 underlies neuronal hyperexcitability and neuropathic pain. Here we show that acute and inflammatory pain behaviour is unchanged in global NavI.3 mutant mice. Surprisingly, neuropathic pain also developed normally in the NavI.3 mutant mouse. To rule out any genetic compensation mechanisms that may have masked the phenotype, we investigated neuropathic pain in two conditional NavI.3 mutant mouse lines. We used NavI.8- Cre mice to delete NavI.3 in nociceptors at E14 and NFH-Cre mice to delete NavI.3 throughout the nervous system postnatally. Again normal levels of neuropathic pain developed after nerve injury in both lines. Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of NavI.3 in global knock-out mice. Our data demonstrate that NavI.3 is neither necessary nor sufficient for the development of nerve-injury related pain.