Immunolocalisation of sodium channel NaG in the intact and injured human peripheral nervous system

Abstract

The voltage-gated ' glial ' sodium channel NaG belongs to a distinct molecular class within the multi-gene family of mammalian sodium channels. Originally found in central and peripheral glia, NaG has since been detected in neurons in rat dorsal root ganglia (DRG) and may play a role in Schwann cell-axon interactions. We have studied the presence of NaG-like immunoreactivity in the intact and injured human peripheral nervous system using a specific affinity-purified antibody. Nerve fibres in normal and injured peripheral nerves and normal skin exhibited intense NaG-immunoreactivity. Numerous NaG-immunoreactive nerve fibres surrounded neuronal cell bodies within postmortem control DRG, and in DRG avulsed from the spinal cord (i.e. after traumatic central axotomy). There were no significant differences in the pattern of NaG immunostaining between control and avulsed DRG, or with delay after injury. Generally, the neuronal cell bodies were only very weakly immunoreactive to NaG, indicating that the NaG immunoreactivity was predominantly in Schwann cells\myelin. In accord, we demonstrated NaG immunostaining in cultured human and rat Schwann cells, and in distal nerve after wallerian degeneration. NaG thus appears to be a useful new marker for Schwann cells in the human PNS, and a role in neuropathy deserves investigation.

Local Anesthetics

“…Pain relief, it appears, is not due to the prolonged pharmacological blockade of ionic Na + channels. There may be other local anesthetic actions that alter neural injury responses, however, such as the inhibition of outgrowth of neurites (Hiruma et al 1999) that are potential loci of hyperexcitability (Devor et al 1993, inhibition of axonal transport (Lavoie et al 1989;Kanai et al 2001), or the destabilization of newly inserted channels within the plasma membrane (Novakovic et al 1998;Coward et al 2001;Gold et al 2003). These actions thus tend to restore the channel population to its pre-injury state.…”

“…Such TTX-R channels are selectively expressed in primary nociceptors (Elliott and Elliott 1993;Rush et al 1998;Cummins et al 1999;DibHajj et al 1999) and contribute critically to increased nociceptive firing after inflammation or injury Porreca et al 1999;Abdulla and Smith 2002;Roza et al 2003;Black et al 2004). Excitability changes after injury may have both rapid and slower components, however, resulting form different underlying processes, such as phosphorylation of existing channels, for the fast responses, and transcriptional regulation or redistribution of existing channels for the slower ones (Devor et al 1993;Novakovic et al 1998;Coward et al 2001).…”