GDNF and NGF reverse changes in repriming of TTX-sensitive Na + currents following axotomy of dorsal root ganglion neurons

Andreas Leffler, Theodore Cummins, Sulayman D. Dib-Hajj, William N. Hormuzdiar, Joel A. Black, Stephen G. Waxman

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Uninjured C-type rat dorsal root ganglion (DRG) neurons predominantly express slowly inactivating TTX-resistant (TTX-R) and slowly repriming TTX-sensitive (TTX-S) Na + currents. After peripheral axotomy, TTX-R current density is reduced and rapidly repriming TTX-S currents emerge and predominate. The change in TTX-S repriming kinetics is paralleled by an increase in the level of transcripts and protein for the Na v1.3 sodium channel α-subunit, which is known to exhibit rapid repriming. Changes in Na + current profile and kinetics in DRG neurons may substantially alter neuronal excitability and could contribute to some states of chronic pain associated with injury of sensory neurons. In the present study, we asked whether glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF), which have been shown to prevent some axotomy-induced changes such as the loss of TTX-R Na + current expression in DRG neurons, can ameliorate the axotomy-induced change in TTX-S Na + current repriming kinetics. We show that intrathecally administered GDNF and NGF, delivered individually, can partially reverse the effect of axotomy on the repriming kinetics of TTX-S Na + currents. When GDNF and NGF were co-administered, the repriming kinetics were fully rescued. We observed parallel effects of GDNF and NGF on the Na v1.3 sodium channel transcript levels in axotomized DRG. Both GDNF and NGF were able to partially reverse the axotomy-induced increase in Na v1.3 mRNA, with GDNF plus NGF producing the largest effect. Our data indicate that both GDNF and NGF can partially reverse an important effect of axotomy on the electrogenic properties of sensory neurons and that their effect is additive.

Original languageEnglish (US)
Pages (from-to)650-658
Number of pages9
JournalJournal of Neurophysiology
Volume88
Issue number2
StatePublished - 2002
Externally publishedYes

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Axotomy
Nerve Growth Factors
Spinal Ganglia
Nerve Growth Factor
Neuroglia
Neurons
Sodium Channels
Sensory Receptor Cells
Chronic Pain
Messenger RNA
Wounds and Injuries

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

GDNF and NGF reverse changes in repriming of TTX-sensitive Na + currents following axotomy of dorsal root ganglion neurons. / Leffler, Andreas; Cummins, Theodore; Dib-Hajj, Sulayman D.; Hormuzdiar, William N.; Black, Joel A.; Waxman, Stephen G.

In: Journal of Neurophysiology, Vol. 88, No. 2, 2002, p. 650-658.

Research output: Contribution to journalArticle

Leffler, Andreas ; Cummins, Theodore ; Dib-Hajj, Sulayman D. ; Hormuzdiar, William N. ; Black, Joel A. ; Waxman, Stephen G. / GDNF and NGF reverse changes in repriming of TTX-sensitive Na + currents following axotomy of dorsal root ganglion neurons. In: Journal of Neurophysiology. 2002 ; Vol. 88, No. 2. pp. 650-658.
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T1 - GDNF and NGF reverse changes in repriming of TTX-sensitive Na + currents following axotomy of dorsal root ganglion neurons

AU - Leffler, Andreas

AU - Cummins, Theodore

AU - Dib-Hajj, Sulayman D.

AU - Hormuzdiar, William N.

AU - Black, Joel A.

AU - Waxman, Stephen G.

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N2 - Uninjured C-type rat dorsal root ganglion (DRG) neurons predominantly express slowly inactivating TTX-resistant (TTX-R) and slowly repriming TTX-sensitive (TTX-S) Na + currents. After peripheral axotomy, TTX-R current density is reduced and rapidly repriming TTX-S currents emerge and predominate. The change in TTX-S repriming kinetics is paralleled by an increase in the level of transcripts and protein for the Na v1.3 sodium channel α-subunit, which is known to exhibit rapid repriming. Changes in Na + current profile and kinetics in DRG neurons may substantially alter neuronal excitability and could contribute to some states of chronic pain associated with injury of sensory neurons. In the present study, we asked whether glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF), which have been shown to prevent some axotomy-induced changes such as the loss of TTX-R Na + current expression in DRG neurons, can ameliorate the axotomy-induced change in TTX-S Na + current repriming kinetics. We show that intrathecally administered GDNF and NGF, delivered individually, can partially reverse the effect of axotomy on the repriming kinetics of TTX-S Na + currents. When GDNF and NGF were co-administered, the repriming kinetics were fully rescued. We observed parallel effects of GDNF and NGF on the Na v1.3 sodium channel transcript levels in axotomized DRG. Both GDNF and NGF were able to partially reverse the axotomy-induced increase in Na v1.3 mRNA, with GDNF plus NGF producing the largest effect. Our data indicate that both GDNF and NGF can partially reverse an important effect of axotomy on the electrogenic properties of sensory neurons and that their effect is additive.

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