Expression of Sodium Channel SNS/PN3 and AnkyrinG mRNAs in the Trigeminal Ganglion after Inferior Alveolar Nerve Injury in the Rat

doi:10.1006/exnr.2000.7437

Experimental Neurology

Volume 164, Issue 2, August 2000, Pages 384-395

https://doi.org/10.1006/exnr.2000.7437 Get rights and content

Abstract

The inferior alveolar nerve is a sensory branch of the trigeminal nerve that is frequently damaged, and such nerve injuries can give rise to persistent paraesthesia and dysaesthesia. The mechanisms behind neuropathic pain following nerve injury is poorly understood. However, remodeling of voltage-gated sodium channels in the neuronal membrane has been proposed as one possible mechanism behind injury-induced ectopic hyperexcitability. The TTX-resistant sodium channel SNS/PN3 has been implicated in the development of neuropathic pain after spinal nerve injury. We here study the effect of chronic axotomy of the inferior alveolar nerve on the expression of SNS/PN3 mRNA in trigeminal sensory neurons. The organization of sodium channels in the neuronal membrane is maintained by binding to ankyrin, which help link the sodium channel to the membrane skeleton. Ankyrin_G, which colocalizes with sodium channels in the initial segments and nodes of Ranvier, and is necessary for normal neuronal sodium channel function, could be essential in the reorganization of the axonal membrane after nerve injury. For this reason, we here study the expression of ankyrin_G in the trigeminal ganglion and the localization of ankyrin_G protein in the inferior alveolar nerve after injury. We show that SNS/PN3 mRNA is down-regulated in small-sized trigeminal ganglion neurons following inferior alveolar nerve injury but that, in contrast to the persistent loss of SNS/PN3 mRNA seen in dorsal root ganglion neurons following sciatic nerve injury, the levels of SNS/PN3 mRNA appear to normalize within a few weeks. We further show that the expression of ankyrin_G mRNA also is downregulated after nerve lesion and that these changes persist for at least 13 weeks. This decrease in the ankyrin_G mRNA expression could play a role in the reorganization of sodium channels within the damaged nerve. The changes in the levels of SNS/PN3 mRNA in the trigeminal ganglion, which follow the time course for hyperexcitability of trigeminal ganglion neurons after inferior alveolar nerve injury, may contribute to the inappropriate firing associated with sensory dysfunction in the orofacial region.

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In the nervous system, sodium channels are synthesised in cell bodies and transported along peripheral nerve fibres where they are inserted into the axonal membrane. Proteins which act to anchor these channels into the membrane, such as ankyrin G, may be involved in their abnormal distribution following nerve injury, and abnormal levels of this structural protein have been reported in injured nerves.9 Ectopic activity in damaged small afferent nerve fibres due to abnormal or upregulated sodium channels is considered to be an important mechanism for neuropathic pain of peripheral origin.
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Regular ArticleExpression of Sodium Channel SNS/PN3 and AnkyrinG mRNAs in the Trigeminal Ganglion after Inferior Alveolar Nerve Injury in the Rat

Abstract

Pain

Mol. Brain Res.

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Pain

Neurosci. Lett.

Pain

Mol. Cell. Neurosci.

Pain

Neurosci. Lett.

Mol. Brain. Res.

J. Oral Maxillofac. Surg.

J. Biol. Chem.

J. Auton. Nerv. Syst.

J. Oral Maxillofac. Surg.

Brain Res.

Dent. Clin. North. Am.

J. Neurophysiol.

Mol. Cell. Neurosci.

Br. J. Oral Maxillofac. Surg.

J. Oral Maxillofac. Surg.

J. Biol. Chem.

Brain Res.

Exp. Neurol.

Brain Res.

Pain

Br. J. Oral Maxillofac. Surg.

A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons

Nature

The spectrin-based membrane skeleton and micron scale organization of the plasma membrane

Annu. Rev. Cell Biol.

Contextual control of trigeminal sensorimotor function

J. Neurosci.

NGF has opposing effects on Na+ channel III and SNS gene expression in spinal sensory neurons

Neuroreport

Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury

J. Neurosci.

Regular Article
Expression of Sodium Channel SNS/PN3 and Ankyrin_G mRNAs in the Trigeminal Ganglion after Inferior Alveolar Nerve Injury in the Rat