title: Upregulation of persistent and ramp sodium current in dorsal horn neurons after spinal cord injury.
abstract: Traumatic spinal cord injury (SCI) results not only in motor impairment, but also in chronic central neuropathic pain, which often is refractory to conventional treatment approaches. Upregulated expression of sodium channel Nav1.3 has been observed within the spinal dorsal horn neurons after SCI, and appears to contribute to neuronal hyperresponsiveness and pain-related behaviors. In this study we characterized the changes in sodium current properties within dorsal horn neurons after contusive SCI. Four weeks after adult male Sprague-Dawley rats underwent T9 spinal cord contusion injury, when behavioral nociceptive thresholds were decreased to both mechanical and thermal stimuli, whole-cell patch-clamp recordings were performed on acutely dissociated lumbar dorsal horn neurons. The cells demonstrated characteristic fast-activating and fast-inactivating sodium currents. SCI led to a shift of the steady-state activation and inactivation of the sodium current towards more depolarized potentials. The shifted steady-state inactivation shows similarities to that obtained from axotomized dorsal root ganglions, which were shown to upregulate Nav1.3. Small slow depolarizations below action potential threshold produced ramp currents, which were markedly enhanced by SCI (from 182 +/- 41 to 338 +/- 55 pA). The density of the noninactivating persistent sodium current was also significantly enhanced in neurons from SCI animals (from 17.4 +/- 3.2 to 27.7 +/- 4.4 pA/pF at 50-70 ms of depolarization). The increased persistent sodium current and ramp current, which are consistent with upregulation of Nav1.3 within dorsal horn neurons, suggest a basis for the hyperresponsiveness of these neurons following SCI.
authors.affiliation: Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Angelika
authors.initials: A
authors.lastname: Lampert
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Hains
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000818:Animals; D002460:Cell Line; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D020671:Posterior Horn Cells / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology*; D014162:Transfection / Q000379:methods; D015854:Up-Regulation
chemical_list: D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C478638:Scn3a protein, rat; D015222:Sodium Channels